Molecular and cellular basis for the unique functioning of Nrf1, an indispensable transcription factor for maintaining cell homoeostasis and organ integrity

Biochemical Journal

Volumn 473, Issue 8, 2016, Pages 961-1000

  Zhang, Yiguo ^a   Xiang, Yuancai ^a  

^a CHONGQING UNIVERSITY   (China)

Author keywords

Cancer; Diabetes; Homoeostasis; Nrf1; Nrf2; Organ integrity.; Redox stress; Topobiology

Indexed keywords

GLUCOSE; INSULIN; TRANSCRIPTION FACTOR NRF1; TRANSCRIPTION FACTOR NRF1 BETA; TRANSCRIPTION FACTOR NRF1 DELTA; TRANSCRIPTION FACTOR NRF1 GAMMA; UNCLASSIFIED DRUG; NRF1 PROTEIN, HUMAN; NUCLEAR RESPIRATORY FACTOR 1; TRANSCRIPTION FACTOR;

AMINO ACID METABOLISM; CARBOXY TERMINAL SEQUENCE; CELL DIFFERENTIATION; DEGENERATIVE DISEASE; DIABETES MELLITUS; FATTY ACID METABOLISM; GLUCOSE METABOLISM; GROWTH; HOMEOSTASIS; INSULIN RELEASE; INSULIN RESISTANCE; LIFE; LIVER CELL CARCINOMA; METABOLIC DISORDER; MOLECULAR BIOLOGY; NONALCOHOLIC FATTY LIVER; NONHUMAN; ORGANOGENESIS; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN STRUCTURE; REDOX STRESS; REVIEW; ANIMAL; CELL MEMBRANE; GENETICS; HUMAN; METABOLISM; PHYSIOLOGY; SIGNAL TRANSDUCTION;

ANIMALS; CELL MEMBRANE; HOMEOSTASIS; HUMANS; NUCLEAR RESPIRATORY FACTOR 1; ORGANOGENESIS; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTORS;

EID: 84975143421     PISSN: 02646021     EISSN: 14708728     Source Type: Journal    
DOI: 10.1042/BJ20151182     Document Type: Review

References (302)

1. Stamler, J.S., Lamas, S. and Fang, F.C. (2001) Nitrosylation: the prototypic redox-based signaling mechanism. Cell 106, 675-683
2. Fang, Y.Z., Yang, S. and Wu, G. (2002) Free radicals, antioxidants, and nutrition. Nutrition 18, 872-879
3. Kensler, T.W., Wakabayashi, N. and Biswal, S. (2007) Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu. Rev. Pharmacol. Toxicol. 47, 89-116
4. Haddad, J.J. (2002) Antioxidant and prooxidant mechanisms in the regulation of redox(y)-sensitive transcription factors. Cell. Signal. 14, 879-897
5. Liu, H., Colavitti, R., Rovira, I.I. and Finkel, T. (2005) Redox-dependent transcriptional regulation. Circ. Res. 97, 967-974
6. Rushmore, T.H., Morton, M.R. and Pickett, C.B. (1991) The antioxidant responsive element: activation by oxidative stress and identification of the DNA consensus sequence required for functional activity. J. Biol. Chem. 266, 11632-11639
7. Kwak, M.K., Wakabayashi, N., Itoh, K., Motohashi, H., Yamamoto, M. and Kensler, T.W. (2003) Modulation of gene expression by cancer chemopreventive dithiolethiones through the Keap1-Nrf2 pathway: identification of novel gene clusters for cell survival. J. Biol. Chem. 278, 8135-8145
8. Nguyen, T., Yang, C.S. and Pickett, C.B. (2004) The pathways and molecular mechanisms regulating Nrf2 activation in response to chemical stress. Free Radic. Biol. Med. 37, 433-441
9. Xiao, H., Lu, F., Stewart, D. and Zhang, Y. (2013) Mechanisms underlying chemopreventive effects of flavonoids via multiple signaling nodes within Nrf2-ARE and AhR-XRE gene regulatory networks. Curr. Chem. Biol. 7, 151-176
10. Sasaki, H., Sato, H., Kuriyama-Matsumura, K., Sato, K., Maebara, K., Wang, H., Tamba, M., Itoh, K., Yamamoto, M. and Bannai, S. (2002) Electrophile response element-mediated induction of the cystine/glutamate exchange transporter gene expression. J. Biol. Chem. 277, 44765-44771
11. Vollrath, V., Wielandt, A.M., Iruretagoyena, M. and Chianale, J. (2006) Role of Nrf2 in the regulation of the Mrp2 (ABCC2) gene. Biochem. J. 395, 599-609
12. Andressoo, J.O. and Hoeijmakers, J.H. (2005) Transcription-coupled repair and premature ageing. Mutat. Res. 577, 179-194
13. Barzilai, A. and Yamamoto, K. (2004) DNA damage responses to oxidative stress. DNA Repair (Amst.) 3, 1109-1115
14. Li, J., Lee, J.M. and Johnson, J.A. (2002) Microarray analysis reveals an antioxidant responsive element-driven gene set involved in conferring protection from an oxidative stress-induced apoptosis in IMR-32 cells. J. Biol. Chem. 277, 388-394
15. Giudice, A. and Montella, M. (2006) Activation of the Nrf2-ARE signaling pathway: a promising strategy in cancer prevention. BioEssays 28, 169-181
16. Beckman, K.B. and Ames, B.N. (1997) Oxidative decay of DNA. J. Biol. Chem. 272, 19633-19636
17. Lombard, D.B., Chua, K.F., Mostoslavsky, R., Franco, S., Gostissa, M. and Alt, F.W. (2005) DNA repair, genome stability, and aging. Cell 120, 497-512
18. Hussain, S.P., Hofseth, L.J. and Harris, C.C. (2003) Radical causes of cancer. Nat. Rev. Cancer 3, 276-285
19. Valko, M., Izakovic, M., Mazur, M., Rhodes, C.J. and Telser, J. (2004) Role of oxygen radicals in DNA damage and cancer incidence. Mol. Cell. Biochem. 266, 37-56
20. Finkel, T. and Holbrook, N.J. (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408, 239-247
21. Balaban, R.S., Nemoto, S. and Finkel, T. (2005) Mitochondria, oxidants, and aging. Cell 120, 483-495
22. Sykiotis, G.P. and Bohmann, D. (2010) Stress-activated cap'n'collar transcription factors in aging and human disease. Sci. Signal. 3,re3
23. Kwak, M.K. and Kensler, T.W. (2011) Targeting NRF2 signaling for cancer chemoprevention. Toxicol. Appl. Pharmacol. 244, 66-76
24. Zhang, Y. (2009) In Molecular and Cellular Control of the Nrf1 Transcription Factor: an Integral Membrane Glycoprotein, Vdm Verlag Dr Müller Publishing House, Saarbrücken
25. Higgins, L.G., Kelleher, M.O., Eggleston, I.M., Itoh, K., Yamamoto, M. and Hayes, J.D. (2009) Transcription factor Nrf2 mediates an adaptive response to sulforaphane that protects fibroblasts in vitro against the cytotoxic effects of electrophiles, peroxides and redox-cycling agents. Toxicol. Appl. Pharmacol. 237, 267-280
26. Chan, K., Lu, R., Chang, J.C. and Kan, Y.W. (1996) NRF2, a member of the NFE2 family of transcription factors, is not essential for murine erythropoiesis, growth, and development. Proc. Natl. Acad. Sci. U.S.A. 93, 13943-13948
27. Xu, C., Huang, M.T., Shen, G., Yuan, X., Lin, W., Khor, T.O., Conney, A.H. and Kong, A.N. (2006) Inhibition of 7,12-dimethylbenz(a)anthracene-induced skin tumorigenesis in C57BL/6 mice by sulforaphane is mediated by nuclear factor E2-related factor 2. Cancer Res. 66, 8293-8296
28. Leung, L., Kwong, M., Hou, S., Lee, C. and Chan, J.Y. (2003) Deficiency of the Nrf1 and Nrf2 transcription factors results in early embryonic lethality and severe oxidative stress. J. Biol. Chem. 278, 48021-48029
29. Farmer, S.C., Sun, C.W., Winnier, G.E., Hogan, B.L. and Townes, T.M. (1997) The bZIP transcription factor LCR-F1 is essential for mesoderm formation in mouse development. Genes Dev. 11, 786-798
30. Chan, J.Y., Kwong, M., Lu, R., Chang, J., Wang, B., Yen, T.S. and Kan, Y.W. (1998) Targeted disruption of the ubiquitous CNC-bZIP transcription factor, Nrf-1, results in anemia and embryonic lethality in mice. EMBO J. 17, 1779-1787
31. Kwong, M., Kan, Y.W. and Chan, J.Y. (1999) The CNC basic leucine zipper factor, Nrf1, is essential for cell survival in response to oxidative stress-inducing agents: role for Nrf1 in ã -gcsL and gss expression in mouse fibroblasts. J. Biol. Chem. 274, 37491-37498
32. Xu, Z., Chen, L., Leung, L., Yen, T.S., Lee, C. and Chan, J.Y. (2005) Liver-specific inactivation of the Nrf1 gene in adult mouse leads to nonalcoholic steatohepatitis and hepatic neoplasia. Proc. Natl. Acad. Sci. U.S.A. 102, 4120-4125
33. Ohtsuji, M., Katsuoka, F., Kobayashi, A., Aburatani, H., Hayes, J.D. and Yamamoto, M. (2008) Nrf1 and Nrf2 play distinct roles in activation of antioxidant response element-dependent genes. J. Biol. Chem. 283, 33554-33562
34. Steffen, J., Seeger, M., Koch, A. and Kruger, E. (2010) Proteasomal degradation is transcriptionally controlled by TCF11 via an ERAD-dependent feedback loop. Mol. Cell 40, 147-158
35. Radhakrishnan, S.K., Lee, C.S., Young, P., Beskow, A., Chan, J.Y. and Deshaies, R.J. (2010) Transcription factor Nrf1 mediates the proteasome recovery pathway after proteasome inhibition in mammalian cells. Mol. Cell 38, 17-28
36. Sha, Z. and Goldberg, A.L. (2014) Proteasome-mediated processing of Nrf1 is essential for coordinate induction of all proteasome subunits and p97. Curr. Biol. 24, 1573-1583
37. Zhang, Y., Ren, Y., Li, S. and Hayes, J.D. (2014) Transcription factor Nrf1 is topologically repartitioned across membranes to enable target gene transactivation through its acidic glucose-responsive domains. PLoS One 9, e93458
38. Zhang, Y., Crouch, D.H., Yamamoto, M. and Hayes, J.D. (2006) Negative regulation of the Nrf1 transcription factor by its N-terminal domain is independent of Keap1: Nrf1, but not Nrf2, is targeted to the endoplasmic reticulum. Biochem. J. 399, 373-385
39. Wang, W. and Chan, J.Y. (2006) Nrf1 is targeted to the endoplasmic reticulum membrane by an N-terminal transmembrane domain: inhibition of nuclear translocation and transacting function. J. Biol. Chem. 281, 19676-19687
40. Zhang, Y., Lucocq, J.M., Yamamoto, M. and Hayes, J.D. (2007) The NHB1 (N-terminal homology box 1) sequence in transcription factor Nrf1 is required to anchor it to the endoplasmic reticulum and also to enable its asparagine-glycosylation. Biochem. J. 408, 161-172
41. Zhang, Y., Lucocq, J.M. and Hayes, J.D. (2009) The Nrf1 CNC/bZIP protein is a nuclear envelope-bound transcription factor that is activated by t-butyl hydroquinone but not by endoplasmic reticulum stressors. Biochem. J. 418, 293-310
42. deBoer, E., Antoniou, M., Mignotte, V., Wall, L. and Grosveld, F. (1988) The human β-globin promoter; nuclear protein factors and erythroid specific induction of transcription. EMBO J. 7, 4203-4212
43. Curtin, P.T., Liu, D.P., Liu, W., Chang, J.C. and Kan, Y.W. (1989) Human β-globin gene expression in transgenic mice is enhanced by a distant DNase I hypersensitive site. Proc. Natl. Acad. Sci. U.S.A. 86, 7082-7086
44. Whitelaw, E., Tsai, S.F., Hogben, P. and Orkin, S.H. (1990) Regulated expression of globin chains and the erythroid transcription factor GATA-1 during erythropoiesis in the developing mouse. Mol. Cell. Biol. 10, 6596-6606
45. Liu, D., Chang, J.C., Moi, P., Liu, W., Kan, Y.W. and Curtin, P.T. (1992) Dissection of the enhancer activity of β-globin 5? DNase I-hypersensitive site 2 in transgenic mice. Proc. Natl. Acad. Sci. U.S.A. 89, 3899-3903
46. Andrews, N.C., Erdjument-Bromage, H., Davidson, M.B., Tempst, P. and Orkin, S.H. (1993) Erythroid transcription factor NF-E2 is a haematopoietic-specific basic-leucine zipper protein. Nature 362, 722-728
47. Moi, P., Chan, K., Asunis, I., Cao, A. and Kan, Y.W. (1994) Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the β-globin locus control region. Proc. Natl. Acad. Sci. U.S.A. 91, 9926-9930
48. Kotkow, K.J. and Orkin, S.H. (1996) Complexity of the erythroid transcription factor NF-E2 as revealed by gene targeting of the mouse p18 NF-E2 locus. Proc. Natl. Acad. Sci. U.S.A. 93, 3514-3518
49. Bean, T.L. and Ney, P.A. (1997) Multiple regions of p45 NF-E2 are required for β-globin gene expression in erythroid cells. Nucleic Acids Res. 25, 2509-2515
50. Andrews, N.C., Kotkow, K.J., Ney, P.A., Erdjument-Bromage, H., Tempst, P. and Orkin, S.H. (1993) The ubiquitous subunit of erythroid transcription factor NF-E2 is a small basic-leucine zipper protein related to the v-maf oncogene. Proc. Natl. Acad. Sci. U.S.A. 90, 11488-11492
51. Andrews, N.C. (1998) The NF-E2 transcription factor. Int. J. Biochem. Cell Biol. 30, 429-432
52. Igarashi, K., Kataoka, K., Itoh, K., Hayashi, N., Nishizawa, M. and Yamamoto, M. (1994) Regulation of transcription by dimerization of erythroid factor NF-E2 p45 with small Maf proteins. Nature 367, 568-572
53. Chan, J.Y., Han, X.L. and Kan, Y.W. (1993) Cloning of Nrf1, an NF-E2-related transcription factor, by genetic selection in yeast. Proc. Natl. Acad. Sci. U.S.A. 90, 11371-11375
54. McKie, J., Johnstone, K., Mattei, M.G. and Scambler, P. (1995) Cloning and mapping of murine Nfe2l1. Genomics 25, 716-719
55. Caterina, J.J., Donze, D., Sun, C.W., Ciavatta, D.J. and Townes, T.M. (1994) Cloning and functional characterization of LCR-F1: a bZIP transcription factor that activates erythroid-specific, human globin gene expression. Nucleic Acids Res. 22, 2383-2391
56. Luna, L., Johnsen, O., Skartlien, A.H., Pedeutour, F., Turc-Carel, C., Prydz, H. and Kolsto, A.B. (1994) Molecular cloning of a putative novel human bZIP transcription factor on chromosome 17q22. Genomics 22, 553-562
57. Husberg, C., Murphy, P., Martin, E. and Kolsto, A.B. (2001) Two domains of the human bZIP transcription factor TCF11 are necessary for transactivation. J. Biol. Chem. 276, 17641-17652
58. Zhang, Y. and Hayes, J.D. (2013) The membrane-topogenic vectorial behaviour of Nrf1 controls its post-translational modification and transactivation activity. Sci. Rep. 3, 2006
59. Zhang, Y., Li, S., Xiang, Y., Qiu, L., Zhao, H. and Hayes, J.D. (2015) The selective post-translational processing of Nrf1 yields distinct isoforms that dictate its activity to differentially regulate target genes. Sci. Rep. 5, e12983
60. Zhang, Y., Lu, Q., Li, S., Xiang, Y., Chen, J. and Ren, Y. (2014) The C-terminal domain (CTD) of Nrf1 negatively regulates this full-length CNC-bZIP factor and its shorter form Nrf1β/LCR-F1; both are also inhibited by the small dominant-negative Nrf1ã /ä isoforms that down-regulates ARE-battery gene expression. PLoS One 9, e109159
61. Wang, W., Kwok, A.M. and Chan, J.Y. (2007) The p65 isoform of Nrf1 is a dominant negative inhibitor of ARE-mediated transcription. J. Biol. Chem. 282, 24670-24678
62. Novotny, V., Prieschl, E.E., Csonga, R., Fabjani, G. and Baumruker, T. (1998) Nrf1 in a complex with fosB, c-jun, junD and ATF2 forms the AP1 component at the TNFα promoter in stimulated mast cells. Nucleic Acids Res. 26, 5480-5485
63. Prieschl, E.E., Novotny, V., Csonga, R., Jaksche, D., Elbe-Burger, A., Thumb, W., Auer, M., Stingl, G. and Baumruker, T. (1998) A novel splice variant of the transcription factor Nrf1 interacts with the TNFα promoter and stimulates transcription. Nucleic Acids Res. 26, 2291-2297
64. Schultz, M.A., Hagan, S.S., Datta, A., Zhang, Y., Freeman, M.L., Sikka, S.C., Abdel-Mageed, A.B. and Mondal, D. (2014) Nrf1 and nrf2 transcription factors regulate androgen receptor transactivation in prostate cancer cells. PLoS One 9, e87204
65. Walker, A.K., See, R., Batchelder, C., Kophengnavong, T., Gronniger, J.T., Shi, Y. and Blackwell, T.K. (2000) A conserved transcription motif suggesting functional parallels between Caenorhabditis elegans SKN-1 and Cap'n'Collar-related basic leucine zipper proteins. J. Biol. Chem. 275, 22166-22171
66. Kwong, E.K., Kim, K.M., Penalosa, P.J. and Chan, J.Y. (2012) Characterization of Nrf1b, a novel isoform of the nuclear factor-erythroid-2 related transcription factor-1 that activates antioxidant response element-regulated genes. PLoS One 7, e48404
67. Chepelev, N.L., Bennitz, J.D., Huang, T., McBride, S. and Willmore, W.G. (2011) The Nrf1 CNC-bZIP protein is regulated by the proteasome and activated by hypoxia. PLoS One 6, e29167
68. Luna, L., Skammelsrud, N., Johnsen, O., Abel, K.J., Weber, B.L., Prydz, H. and Kolsto, A.B. (1995) Structural organization and mapping of the human TCF11 gene. Genomics 27, 237-244
69. McMahon, M., Itoh, K., Yamamoto, M., Chanas, S.A., Henderson, C.J., McLellan, L.I., Wolf, C.R., Cavin, C. and Hayes, J.D. (2001) The Cap'n'Collar basic leucine zipper transcription factor Nrf2 (NF-E2 p45-related factor 2) controls both constitutive and inducible expression of intestinal detoxification and glutathione biosynthetic enzymes. Cancer Res. 61, 3299-3307
70. Williams, L.M., Timme-Laragy, A.R., Goldstone, J.V., McArthur, A.G., Stegeman, J.J., Smolowitz, R.M. and Hahn, M.E. (2013) Developmental expression of the Nfe2-related factor (Nrf) transcription factor family in the zebrafish, Danio rerio. PLoS One 8, e79574
71. Virbasius, C.A., Virbasius, J.V. and Scarpulla, R.C. (1993) NRF-1, an activator involved in nuclear-mitochondrial interactions, utilizes a new DNA-binding domain conserved in a family of developmental regulators. Genes Dev. 7, 2431-2445
72. Becker, T.S., Burgess, S.M., Amsterdam, A.H., Allende, M.L. and Hopkins, N. (1998) not really finished is crucial for development of the zebrafish outer retina and encodes a transcription factor highly homologous to human nuclear respiratory factor-1 and avian initiation binding repressor. Development 125, 4369-4378
73. Perez-Garcia, A., Snoeijers, S.S., Joosten, M.H., Goosen, T. and De Wit, P.J. (2001) Expression of the Avirulence gene Avr9 of the fungal tomato pathogen Cladosporium fulvum is regulated by the global nitrogen response factor NRF1. Mol. Plant Microbe Interact. 14, 316-325
74. Murray, J.M. and Johnson, D.I. (2000) Isolation and characterization of Nrf1p, a novel negative regulator of the Cdc42p GTPase in Schizosaccharomyces pombe. Genetics 154, 155-165
75. Zhang, Y., Crouch, D.H. and Hayes, J.D. (2004) Identification of functional domains in the p45 nuclear factor-erythroid 2-related transcription factor 1 (Nrf1). The 10th SCBA International Symposium, Beijing, China, 18-23 July 2004, p. 247
76. Zhang, Y. and Hayes, J.D. (2010) Identification of topological determinants in the N-terminal domain of transcription factor Nrf1 that control its orientation in the endoplasmic reticulum membrane. Biochem. J. 430, 497-510
77. Rupert, P.B., Daughdrill, G.W., Bowerman, B. and Matthews, B.W. (1998) A new DNA-binding motif in the Skn-1 binding domain-DNA complex. Nat. Struct. Biol. 5, 484-491
78. Johnsen, O., Murphy, P., Prydz, H. and Kolsto, A.B. (1998) Interaction of the CNC-bZIP factor TCF11/LCR-F1/Nrf1 with MafG: binding-site selection and regulation of transcription. Nucleic Acids Res. 26, 512-520
79. Itoh, K., Wakabayashi, N., Katoh, Y., Ishii, T., Igarashi, K., Engel, J.D. and Yamamoto, M. (1999) Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev. 13, 76-86
80. Johnsen, O., Skammelsrud, N., Luna, L., Nishizawa, M., Prydz, H. and Kolsto, A.B. (1996) Small Maf proteins interact with the human transcription factor TCF11/Nrf1/LCR-F1. Nucleic Acids Res. 24, 4289-4297
81. Venugopal, R. and Jaiswal, A.K. (1996) Nrf1 and Nrf2 positively and c-Fos and Fra1 negatively regulate the human antioxidant response element-mediated expression of NAD(P)H:quinone oxidoreductase1 gene. Proc. Natl. Acad. Sci. U.S.A. 93, 14960-14965
82. Nioi, P., McMahon, M., Itoh, K., Yamamoto, M. and Hayes, J.D. (2003) Identification of a novel Nrf2-regulated antioxidant response element (ARE) in the mouse NAD(P)H:quinone oxidoreductase 1 gene: reassessment of the ARE consensus sequence. Biochem. J. 374, 337-348
83. Kimura, M., Yamamoto, T., Zhang, J., Itoh, K., Kyo, M., Kamiya, T., Aburatani, H., Katsuoka, F., Kurokawa, H., Tanaka, T. et al. (2007) Molecular basis distinguishing the DNA binding profile of Nrf2-Maf heterodimer from that of Maf homodimer. J. Biol. Chem. 282, 33681-33690
84. Kurokawa, H., Motohashi, H., Sueno, S., Kimura, M., Takagawa, H., Kanno, Y., Yamamoto, M. and Tanaka, T. (2009) Structural basis of alternative DNA recognition by Maf transcription factors. Mol. Cell. Biol. 29, 6232-6244
85. Motohashi, H., O'Connor, T., Katsuoka, F., Engel, J.D. and Yamamoto, M. (2002) Integration and diversity of the regulatory network composed of Maf and CNC families of transcription factors. Gene 294, 1-12
86. Yamamoto, T., Kyo, M., Kamiya, T., Tanaka, T., Engel, J.D., Motohashi, H. and Yamamoto, M. (2006) Predictive base substitution rules that determine the binding and transcriptional specificity of Maf recognition elements. Genes Cells 11, 575-591
87. Venugopal, R. and Jaiswal, A.K. (1998) Nrf2 and Nrf1 in association with Jun proteins regulate antioxidant response element-mediated expression and coordinated induction of genes encoding detoxifying enzymes. Oncogene 17, 3145-3156
88. Yang, H., Magilnick, N., Lee, C., Kalmaz, D., Ou, X., Chan, J.Y. and Lu, S.C. (2005) Nrf1 and Nrf2 regulate rat glutamate-cysteine ligase catalytic subunit transcription indirectly via NF-êB and AP-1. Mol. Cell. Biol. 25, 5933-5946
89. Newman, J.R. and Keating, A.E. (2003) Comprehensive identification of human bZIP interactions with coiled-coil arrays. Science 300, 2097-2101
90. Husberg, C., Murphy, P., Bjorgo, E., Kalland, K.H. and Kolsto, A.B. (2003) Cellular localisation and nuclear export of the human bZIP transcription factor TCF11. Biochim. Biophys. Acta 1640, 143-151
91. Narayanan, K., Ramachandran, A., Peterson, M.C., Hao, J., Kolsto, A.B., Friedman, A.D. and George, A. (2004) The CCAAT enhancer-binding protein (C/EBP)β and Nrf1 interact to regulate dentin sialophosphoprotein (DSPP) gene expression during odontoblast differentiation. J. Biol. Chem. 279, 45423-45432
92. Marini, M.G., Chan, K., Casula, L., Kan, Y.W., Cao, A. and Moi, P. (1997) hMAF, a small human transcription factor that heterodimerizes specifically with Nrf1 and Nrf2. J. Biol. Chem. 272, 16490-16497
93. Nioi, P., Nguyen, T., Sherratt, P.J. and Pickett, C.B. (2005) The carboxy-terminal neh3 domain of Nrf2 is required for transcriptional activation. Mol. Cell. Biol. 25, 10895-10906
94. Tsuchiya, Y., Taniguchi, H., Ito, Y., Morita, T., Karim, M.R., Ohtake, N., Fukagai, K., Ito, T., Okamuro, S., Iemura, S. et al. (2013) The CK2-Nrf1 axis controls the clearance of ubiquitinated proteins by regulating proteasome gene expression. Mol. Cell. Biol. 33, 3461-3472
95. Huang, C.F., Wang, Y.C., Tsao, D.A., Tung, S.F., Lin, Y.S. and Wu, C.W. (2000) Antagonism between members of the CNC-bZIP family and the immediate-early protein IE2 of human cytomegalovirus. J. Biol. Chem. 275, 12313-12320
96. Wu, J.L., Lin, Y.S., Yang, C.C., Lin, Y.J., Wu, S.F., Lin, Y.T. and Huang, C.F. (2009) MCRS2 represses the transactivation activities of Nrf1. BMC Cell Biol. 10, 9
97. McMahon, M., Itoh, K., Yamamoto, M. and Hayes, J.D. (2003) Keap1-dependent proteasomal degradation of transcription factor Nrf2 contributes to the negative regulation of antioxidant response element-driven gene expression. J. Biol. Chem. 278, 21592-21600
98. Kobayashi, A., Kang, M.I., Okawa, H., Ohtsuji, M., Zenke, Y., Chiba, T., Igarashi, K. and Yamamoto, M. (2004) Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2. Mol. Cell. Biol. 24, 7130-7139
99. Tong, K.I., Kobayashi, A., Katsuoka, F. and Yamamoto, M. (2006) Two-site substrate recognition model for the Keap1-Nrf2 system: a hinge and latch mechanism. Biol. Chem. 387, 1311-1320
100. 100 Padmanabhan, B., Tong, K.I., Ohta, T., Nakamura, Y., Scharlock, M., Ohtsuji, M., Kang, M.I., Kobayashi, A., Yokoyama, S. and Yamamoto, M. (2006) Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer. Mol. Cell 21, 689-700
101. McMahon, M., Thomas, N., Itoh, K., Yamamoto, M. and Hayes, J.D. (2006) Dimerization of substrate adaptors can facilitate cullin-mediated ubiquitylation of proteins by a "tethering" mechanism: a two-site interaction model for the Nrf2-Keap1 complex. J. Biol. Chem. 281, 24756-24768
102. Lo, S.C., Li, X., Henzl, M.T., Beamer, L.J. and Hannink, M. (2006) Structure of the Keap1:Nrf2 interface provides mechanistic insight into Nrf2 signaling. EMBO J. 25, 3605-3617
103. Ogura, T., Tong, K.I., Mio, K., Maruyama, Y., Kurokawa, H., Sato, C. and Yamamoto, M. (2010) Keap1 is a forked-stem dimer structure with two large spheres enclosing the intervening, double glycine repeat, and C-terminal domains. Proc. Natl. Acad. Sci. U.S.A. 107, 2842-2847
104. Sykiotis, G.P. and Bohmann, D. (2008) Keap1/Nrf2 signaling regulates oxidative stress tolerance and lifespan in Drosophila. Dev. Cell 14, 76-85
105. Hochmuth, C.E., Biteau, B., Bohmann, D. and Jasper, H. (2011) Redox regulation by Keap1 and Nrf2 controls intestinal stem cell proliferation in Drosophila. Cell Stem Cell 8, 188-199
106. Tsuchiya, Y., Morita, T., Kim, M., Iemura, S., Natsume, T., Yamamoto, M. and Kobayashi, A. (2011) Dual regulation of the transcriptional activity of Nrf1 by β-TrCP- and Hrd1-dependent degradation mechanisms. Mol. Cell. Biol. 31, 4500-4512
107. Biswas, M., Phan, D., Watanabe, M. and Chan, J.Y. (2011) The Fbw7 tumor suppressor regulates nuclear factor E2 related factor 1 (Nrf1) transcription factor turnover through proteasome-mediated proteolysis. J. Biol. Chem. 286, 39282-39289
108. Zhao, R., Hou, Y., Xue, P., Woods, C.G., Fu, J., Feng, B., Guan, D., Sun, G., Chan, J.Y., Waalkes, M.P. et al. (2011) Long isoforms of NRF1 contribute to arsenic-induced antioxidant response in human keratinocytes. Environ. Health Perspect. 119, 56-62
109. Zhao, R., Hou, Y., Zhang, Q., Woods, C.G., Xue, P., Fu, J., Yarborough, K., Guan, D., Andersen, M.E. and Pi, J. (2012) Cross-regulations among NRFs and KEAP1 and effects of their silencing on arsenic-induced antioxidant response and cytotoxicity in human keratinocytes. Environ. Health Perspect. 120, 583-589
110. McMahon, M., Thomas, N., Itoh, K., Yamamoto, M. and Hayes, J.D. (2004) Redox-regulated turnover of Nrf2 is determined by at least two separate protein domains, the redox-sensitive Neh2 degron and the redox-insensitive Neh6 degron. J. Biol. Chem. 279, 31556-31567
111. Huang, H.C., Nguyen, T. and Pickett, C.B. (2002) Phosphorylation of Nrf2 at Ser-40 by protein kinase C regulates antioxidant response element-mediated transcription. J. Biol. Chem. 277, 42769-42774
112. Katoh, Y., Itoh, K., Yoshida, E., Miyagishi, M., Fukamizu, A. and Yamamoto, M. (2001) Two domains of Nrf2 cooperatively bind CBP, a CREB binding protein, and synergistically activate transcription. Genes Cells 6, 857-868
113. Zhang, J., Hosoya, T., Maruyama, A., Nishikawa, K., Maher, J.M., Ohta, T., Motohashi, H., Fukamizu, A., Shibahara, S., Itoh, K. et al. (2007) Nrf2 Neh5 domain is differentially utilized in the transactivation of cytoprotective genes. Biochem. J. 404, 459-466
114. Kim, J.H., Yu, S., Chen, J.D. and Kong, A.N. (2012) The nuclear cofactor RAC3/AIB1/SRC-3 enhances Nrf2 signaling by interacting with transactivation domains. Oncogene 32, 514-527
115. Wang, H., Liu, K., Geng, M., Gao, P., Wu, X., Hai, Y., Li, Y., Li, Y., Luo, L., Hayes, J.D. et al. (2013) RXRα inhibits the NRF2-ARE signaling pathway through a direct interaction with the Neh7 domain of NRF2. Cancer Res. 73, 3097-3108
116. Biswas, M., Kwong, E.K., Park, E., Nagra, P. and Chan, J.Y. (2013) Glycogen synthase kinase 3 regulates expression of nuclear factor-erythroid-2 related transcription factor-1 (Nrf1) and inhibits pro-survival function of Nrf1. Exp. Cell Res. 319, 1922-1931
117. Chowdhry, S., Zhang, Y., McMahon, M., Sutherland, C., Cuadrado, A. and Hayes, J.D. (2013) Nrf2 is controlled by two distinct β-TrCP recognition motifs in its Neh6 domain, one of which can be modulated by GSK-3 activity. Oncogene 32, 3765-3781
118. An, J.H., Vranas, K., Lucke, M., Inoue, H., Hisamoto, N., Matsumoto, K. and Blackwell, T.K. (2005) Regulation of the Caenorhabditis elegans oxidative stress defense protein SKN-1 by glycogen synthase kinase-3. Proc. Natl. Acad. Sci. U.S.A. 102, 16275-16280
119. Chen, J., Liu, X., Lu, F., Liu, X., Ru, Y., Ren, Y., Yao, L. and Zhang, Y. (2015) Transcription factor Nrf1 is negatively regulated by its O-GlcNAcylation status. FEBS Lett. 589, 2347-2358
120. von Heijne, G. (2006) Membrane-protein topology. Nat. Rev. Mol. Cell Biol. 7, 909-918
121. Dowhan, W. and Bogdanov, M. (2009) Lipid-dependent membrane protein topogenesis. Annu. Rev. Biochem. 78, 515-540
122. Nouhi, Z., Chevillard, G., Derjuga, A. and Blank, V. (2007) Endoplasmic reticulum association and N-linked glycosylation of the human Nrf3 transcription factor. FEBS Lett. 581, 5401-5406
123. Zhang, Y., Kobayashi, A., Yamamoto, M. and Hayes, J.D. (2009) The Nrf3 transcription factor is a membrane-bound glycoprotein targeted to the endoplasmic reticulum through its N-terminal homology box 1 sequence. J. Biol. Chem. 284, 3195-3210
124. Grimberg, K.B., Beskow, A., Lundin, D., Davis, M.M. and Young, P. (2011) Basic leucine zipper protein Cnc-C is a substrate and transcriptional regulator of the Drosophila 26S proteasome. Mol. Cell. Biol. 31, 897-909
125. Staab, T.A., Griffen, T.C., Corcoran, C., Evgrafov, O., Knowles, J.A. and Sieburth, D. (2013) The conserved SKN-1/Nrf2 stress response pathway regulates synaptic function in Caenorhabditis elegans. PLoS Genet. 9, e1003354
126. Glover-Cutter, K.M., Lin, S. and Blackwell, T.K. (2013) Integration of the unfolded protein and oxidative stress responses through SKN-1/Nrf. PLoS Genet. 9, e1003701
127. Radhakrishnan, S.K., den Besten, W. and Deshaies, R.J. (2014) p97-dependent retrotranslocation and proteolytic processing govern formation of active Nrf1 upon proteasome inhibition. eLife 3, e01856
128. Johnson, P.R., Swanson, R., Rakhilina, L. and Hochstrasser, M. (1998) Degradation signal masking by heterodimerization of MATα2 and MATa1 blocks their mutual destruction by the ubiquitin-proteasome pathway. Cell 94, 217-227
129. Zattas, D. and Hochstrasser, M. (2015) Ubiquitin-dependent protein degradation at the yeast endoplasmic reticulum and nuclear envelope. Crit. Rev. Biochem. Mol. Biol. 50, 1-17
130. Kacena, M.A., Gundberg, C.M., Nelson, T. and Horowitz, M.C. (2005) Loss of the transcription factor p45 NF-E2 results in a developmental arrest of megakaryocyte differentiation and the onset of a high bone mass phenotype. Bone 36, 215-223
131. Kobayashi, A., Ito, E., Toki, T., Kogame, K., Takahashi, S., Igarashi, K., Hayashi, N. and Yamamoto, M. (1999) Molecular cloning and functional characterization of a new Cap'n'collar family transcription factor Nrf3. J. Biol. Chem. 274, 6443-6452
132. Etchevers, H.C. (2005) The cap 'n' collar family member NF-E2-related factor 3 (Nrf3) is expressed in mesodermal derivatives of the avian embryo. Int. J. Dev. Biol. 49, 363-367
133. Derjuga, A., Gourley, T.S., Holm, T.M., Heng, H.H., Shivdasani, R.A., Ahmed, R., Andrews, N.C. and Blank, V. (2004) Complexity of CNC transcription factors as revealed by gene targeting of the Nrf3 locus. Mol. Cell. Biol. 24, 3286-3294
134. Murphy, P. and Kolsto, A. (2000) Expression of the bZIP transcription factor TCF11 and its potential dimerization partners during development. Mech. Dev. 97, 141-148
135. Chen, L., Kwong, M., Lu, R., Ginzinger, D., Lee, C., Leung, L. and Chan, J.Y. (2003) Nrf1 is critical for redox balance and survival of liver cells during development. Mol. Cell. Biol. 23, 4673-4686
136. Oh, D.H., Rigas, D., Cho, A. and Chan, J.Y. (2012) Deficiency in the nuclear-related factor erythroid 2 transcription factor (Nrf1) leads to genetic instability. FEBS J. 279, 4121-4130
137. Lee, C.S., Ho, D.V. and Chan, J.Y. (2013) Nuclear factor-erythroid 2-related factor 1 regulates expression of proteasome genes in hepatocytes and protects against endoplasmic reticulum stress and steatosis in mice. FEBS J. 280, 3609-3620
138. Tsujita, T., Peirce, V., Baird, L., Matsuyama, Y., Takaku, M., Walsh, S.V., Griffin, J.L., Uruno, A., Yamamoto, M. and Hayes, J.D. (2014) Transcription factor Nrf1 negatively regulates the cystine/glutamate transporter and lipid-metabolizing enzymes. Mol. Cell. Biol. 34, 3800-3816
139. Masuoka, H.C. and Townes, T.M. (2002) Targeted disruption of the activating transcription factor 4 gene results in severe fetal anemia in mice. Blood 99, 736-745
140. Shavit, J.A., Motohashi, H., Onodera, K., Akasaka, J., Yamamoto, M. and Engel, J.D. (1998) Impaired megakaryopoiesis and behavioral defects in mafG-null mutant mice. Genes Dev. 12, 2164-2174
141. Onodera, K., Shavit, J.A., Motohashi, H., Katsuoka, F., Akasaka, J.E., Engel, J.D. and Yamamoto, M. (1999) Characterization of the murine mafF gene. J. Biol. Chem. 274, 21162-21169
142. Yamazaki, H., Katsuoka, F., Motohashi, H., Engel, J.D. and Yamamoto, M. (2012) Embryonic lethality and fetal liver apoptosis in mice lacking all three small Maf proteins. Mol. Cell. Biol. 32, 808-816
143. Hilberg, F., Aguzzi, A., Howells, N. and Wagner, E.F. (1993) c-jun is essential for normal mouse development and hepatogenesis. Nature 365, 179-181
144. Eferl, R., Sibilia, M., Hilberg, F., Fuchsbichler, A., Kufferath, I., Guertl, B., Zenz, R., Wagner, E.F. and Zatloukal, K. (1999) Functions of c-Jun in liver and heart development. J. Cell. Biol. 145, 1049-1061
145. Behrens, A., Sibilia, M., David, J.P., Mohle-Steinlein, U., Tronche, F., Schutz, G. and Wagner, E.F. (2002) Impaired postnatal hepatocyte proliferation and liver regeneration in mice lacking c-jun in the liver. EMBO J. 21, 1782-1790
146. Meixner, A., Karreth, F., Kenner, L., Penninger, J.M. and Wagner, E.F. (2010) Jun and JunD-dependent functions in cell proliferation and stress response. Cell Death Differ. 17, 1409-1419
147. Lee, C.S., Lee, C., Hu, T., Nguyen, J.M., Zhang, J., Martin, M.V., Vawter, M.P., Huang, E.J. and Chan, J.Y. (2011) Loss of nuclear factor E2-related factor 1 in the brain leads to dysregulation of proteasome gene expression and neurodegeneration. Proc. Natl. Acad. Sci. U.S.A. 108, 8408-8413
148. Hertel, M., Braun, S., Durka, S., Alzheimer, C. and Werner, S. (2002) Upregulation and activation of the Nrf-1 transcription factor in the lesioned hippocampus. Eur. J. Neurosci. 15, 1707-1711
149. Shivdasani, R.A. and Orkin, S.H. (1995) Erythropoiesis and globin gene expression in mice lacking the transcription factor NF-E2. Proc. Natl. Acad. Sci. U.S.A. 92, 8690-8694
150. Itoh, K., Chiba, T., Takahashi, S., Ishii, T., Igarashi, K., Katoh, Y., Oyake, T., Hayashi, N., Satoh, K., Hatayama, I. et al. (1997) An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem. Biophys. Res. Commun. 236, 313-322
151. Sun, J., Hoshino, H., Takaku, K., Nakajima, O., Muto, A., Suzuki, H., Tashiro, S., Takahashi, S., Shibahara, S., Alam, J. et al. (2002) Hemoprotein Bach1 regulates enhancer availability of heme oxygenase-1 gene. EMBO J. 21, 5216-5224
152. Kobayashi, A., Ohta, T. and Yamamoto, M. (2004) Unique function of the Nrf2-Keap1 pathway in the inducible expression of antioxidant and detoxifying enzymes. Methods Enzymol. 378, 273-286
153. Muto, A., Tashiro, S., Nakajima, O., Hoshino, H., Takahashi, S., Sakoda, E., Ikebe, D., Yamamoto, M. and Igarashi, K. (2004) The transcriptional programme of antibody class switching involves the repressor Bach2. Nature 429, 566-571
154. Kobayashi, A., Tsukide, T., Miyasaka, T., Morita, T., Mizoroki, T., Saito, Y., Ihara, Y., Takashima, A., Noguchi, N., Fukamizu, A. et al. (2011) Central nervous system-specific deletion of transcription factor Nrf1 causes progressive motor neuronal dysfunction. Genes Cells 16, 692-703
155. Katsuoka, F., Motohashi, H., Tamagawa, Y., Kure, S., Igarashi, K., Engel, J.D. and Yamamoto, M. (2003) Small Maf compound mutants display central nervous system neuronal degeneration, aberrant transcription, and Bach protein mislocalization coincident with myoclonus and abnormal startle response. Mol. Cell. Biol. 23, 1163-1174
156. Franceschi, R.T., Iyer, B.S. and Cui, Y. (1994) Effects of ascorbic acid on collagen matrix formation and osteoblast differentiation in murine MC3T3-E1 cells. J. Bone Miner. Res. 9, 843-854
157. Hadzir, S.N., Ibrahim, S.N., Abdul Wahab, R.M., Zainol Abidin, I.Z., Senafi, S., Ariffin, Z.Z., Abdul Razak, M. and Zainal Ariffin, S.H. (2014) Ascorbic acid induces osteoblast differentiation of human suspension mononuclear cells. Cytotherapy 16, 674-682
158. Xing, W., Singgih, A., Kapoor, A., Alarcon, C.M., Baylink, D.J. and Mohan, S. (2007) Nuclear factor-E2-related factor-1 mediates ascorbic acid induction of osterix expression via interaction with antioxidant-responsive element in bone cells. J. Biol. Chem. 282, 22052-22061
159. Mohan, S., Kapoor, A., Singgih, A., Zhang, Z., Taylor, T., Yu, H., Chadwick, R.B., Chung, Y.S., Donahue, L.R., Rosen, C. et al. (2005) Spontaneous fractures in the mouse mutant sfx are caused by deletion of the gulonolactone oxidase gene, causing vitamin C deficiency. J. Bone Miner. Res. 20, 1597-1610
160. Hinoi, E., Fujimori, S., Wang, L., Hojo, H., Uno, K. and Yoneda, Y. (2006) Nrf2 negatively regulates osteoblast differentiation via interfering with Runx2-dependent transcriptional activation. J. Biol. Chem. 281, 18015-18024
161. Hinoi, E., Takarada, T., Fujimori, S., Wang, L., Iemata, M., Uno, K. and Yoneda, Y. (2007) Nuclear factor E2 p45-related factor 2 negatively regulates chondrogenesis. Bone 40, 337-344
162. Kim, J., Xing, W., Wergedal, J., Chan, J.Y. and Mohan, S. (2010) Targeted disruption of nuclear factor erythroid-derived 2-like 1 in osteoblasts reduces bone size and bone formation in mice. Physiol. Genomics 40, 100-110
163. Chevillard, G., Nouhi, Z., Anna, D., Paquet, M. and Blank, V. (2010) Nrf3-deficient mice are not protected against acute lung and adipose tissue damages induced by butylated hydroxytoluene. FEBS Lett. 584, 923-928
164. Biswas, M. and Chan, J.Y. (2010) Role of Nrf1 in antioxidant response element-mediated gene expression and beyond. Toxicol. Appl. Pharmacol. 244, 16-20
165. Hayes, J.D. and McMahon, M. (2006) The double-edged sword of Nrf2: subversion of redox homeostasis during the evolution of cancer. Mol. Cell 21, 732-734
166. Koch, A., Steffen, J. and Kruger, E. (2011) TCF11 at the crossroads of oxidative stress and the ubiquitin proteasome system. Cell Cycle 10, 1200-1207
167. Hayes, J.D., McMahon, M., Chowdhry, S. and Dinkova-Kostova, A.T. (2010) Cancer chemoprevention mechanisms mediated through the Keap1-Nrf2 pathway. Antioxid. Redox Signal. 13, 1713-1748
168. Hayes, J.D. and McMahon, M. (2009) NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer. Trends Biochem. Sci. 34, 176-188
169. Wakabayashi, N., Itoh, K., Wakabayashi, J., Motohashi, H., Noda, S., Takahashi, S., Imakado, S., Kotsuji, T., Otsuka, F., Roop, D.R. et al. (2003) Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation. Nat. Genet. 35, 238-245
170. Myhrstad, M.C., Husberg, C., Murphy, P., Nordstrom, O., Blomhoff, R., Moskaug, J.O. and Kolsto, A.B. (2001) TCF11/Nrf1 overexpression increases the intracellular glutathione level and can transactivate the ã -glutamylcysteine synthetase (GCS) heavy subunit promoter. Biochim. Biophys. Acta 1517, 212-219
171. Hayes, J.D. and Strange, R.C. (2000) Glutathione S-transferase polymorphisms and their biological consequences. Pharmacology 61, 154-166
172. Zhang, H., Liu, H., Iles, K.E., Liu, R.M., Postlethwait, E.M., Laperche, Y. and Forman, H.J. (2006) 4-Hydroxynonenal induces rat ã -glutamyl transpeptidase through MAPK mediated EpRE/Nrf2 signaling. Am. J. Respir. Cell Mol. Biol. 34, 174-181
173. Angeloni, C., Motori, E., Fabbri, D., Malaguti, M., Leoncini, E., Lorenzini, A. and Hrelia, S. (2011) H2 O2 preconditioning modulates phase II enzymes through p38 MAPK and PI3K/Akt activation. Am. J. Physiol. Heart. Circ. Physiol. 300, H2196-H2205
174. Lee, E.K., Kim, J.A., Park, S.J., Kim, J.K., Heo, K., Yang, K.M. and Son, T.G. (2013) Low-dose radiation activates Nrf1/2 through reactive species and the 2+ /ERK1/2 signaling pathway in human skin fibroblast cells. BMB Rep. 46, 258-263
175. Chepelev, N.L., Enikanolaiye, M.I., Chepelev, L.L., Almohaisen, A., Chen, Q., Scoggan, K.A., Coughlan, M.C., Cao, X.L., Jin, X. and Willmore, W.G. (2013) Bisphenol A activates the Nrf1/2-antioxidant response element pathway in HEK 293 cells. Chem. Res. Toxicol. 26, 498-506
176. Chepelev, N.L., Zhang, H., Liu, H., McBride, S., Seal, A.J., Morgan, T.E., Finch, C.E., Willmore, W.G., Davies, K.J. and Forman, H.J. (2013) Competition of nuclear factor-erythroid 2 factors related transcription factor isoforms, Nrf1 and Nrf2, in antioxidant enzyme induction. Redox Biol. 1, 183-189
177. Song, M.O., Mattie, M.D., Lee, C.H. and Freedman, J.H. (2014) The role of Nrf1 and Nrf2 in the regulation of copper-responsive transcription. Exp. Cell Res. 322, 39-50
178. Siegel, D., Bolton, E.M., Burr, J.A., Liebler, D.C. and Ross, D. (1997) The reduction of α-tocopherolquinone by human NAD(P)H: quinone oxidoreductase: the role of α-tocopherolhydroquinone as a cellular antioxidant. Mol. Pharmacol. 52, 300-305
179. Vasiliou, V., Qamar, L., Pappa, A., Sophos, N.A. and Petersen, D.R. (2003) Involvement of the electrophile responsive element and p53 in the activation of hepatic stellate cells as a response to electrophile menadione. Arch. Biochem. Biophys. 413, 164-171
180. Hernandez-Montes, E., Pollard, S.E., Vauzour, D., Jofre-Montseny, L., Rota, C., Rimbach, G., Weinberg, P.D. and Spencer, J.P. (2006) Activation of glutathione peroxidase via Nrf1 mediates genistein's protection against oxidative endothelial cell injury. Biochem. Biophys. Res. Commun. 346, 851-859
181. Han, W., Ming, M., Zhao, R., Pi, J., Wu, C. and He, Y.Y. (2012) Nrf1 CNC-bZIP protein promotes cell survival and nucleotide excision repair through maintaining glutathione homeostasis. J. Biol. Chem. 287, 18788-18795
182. Thompson, J.A., White, C.C., Cox, D.P., Chan, J.Y., Kavanagh, T.J., Fausto, N. and Franklin, C.C. (2009) Distinct Nrf1/2-independent mechanisms mediate 3+ -induced glutamate-cysteine ligase subunit gene expression in murine hepatocytes. Free Radical Biol. Med. 46, 1614-1625
183. Zhu, W., Jia, Q., Wang, Y., Zhang, Y. and Xia, M. (2012) The anthocyanin cyanidin-3-O-β-glucoside, a flavonoid, increases hepatic glutathione synthesis and protects hepatocytes against reactive oxygen species during hyperglycemia: involvement of a cAMP-PKA-dependent signaling pathway. Free Radical Biol. Med. 52, 314-327
184. Wasserman, W.W. and Fahl, W.E. (1997) Functional antioxidant responsive elements. Proc. Natl. Acad. Sci. U.S.A. 94, 5361-5366
185. Mulcahy, R.T., Wartman, M.A., Bailey, H.H. and Gipp, J.J. (1997) Constitutive and β-naphthoflavone-induced expression of the human ã -glutamylcysteine synthetase heavy subunit gene is regulated by a distal antioxidant response element/TRE sequence. J. Biol. Chem. 272, 7445-7454
186. Moinova, H.R. and Mulcahy, R.T. (1998) An electrophile responsive element (EpRE) regulates β-naphthoflavone induction of the human ã -glutamylcysteine synthetase regulatory subunit gene: constitutive expression is mediated by an adjacent AP-1 site. J. Biol. Chem. 273, 14683-14689
187. Wang, W. and Jaiswal, A.K. (2006) Nuclear factor Nrf2 and antioxidant response element regulate NRH:quinone oxidoreductase 2 (NQO2) gene expression and antioxidant induction. Free Radical Biol. Med. 40, 1119-1130
188. Zhang, H. and Forman, H.J. (2010) Reexamination of the electrophile response element sequences and context reveals a lack of consensus in gene function. Biochim. Biophys. Acta 1799, 496-501
189. Forman, H.J., Dickinson, D.A. and Iles, K.E. (2003) HNE-signaling pathways leading to its elimination. Mol. Aspects Med. 24, 189-194
190. Xie, T., Belinsky, M., Xu, Y. and Jaiswal, A.K. (1995) ARE- and TRE-mediated regulation of gene expression: response to xenobiotics and antioxidants. J. Biol. Chem. 270, 6894-6900
191. Dickinson, D.A., Iles, K.E., Zhang, H., Blank, V. and Forman, H.J. (2003) Curcumin alters EpRE and AP-1 binding complexes and elevates glutamate-cysteine ligase gene expression. FASEB J. 17, 473-475
192. Levy, S., Jaiswal, A.K. and Forman, H.J. (2009) The role of c-Jun phosphorylation in EpRE activation of phase II genes. Free Radical Biol. Med. 47, 1172-1179
193. Kensler, T.W., Egner, P.A., Agyeman, A.S., Visvanathan, K., Groopman, J.D., Chen, J.G., Chen, T.Y., Fahey, J.W. and Talalay, P. (2013) Keap1-nrf2 signaling: a target for cancer prevention by sulforaphane. Top. Curr. Chem. 329, 163-177
194. Schafer, M., Dutsch, S., auf dem Keller, U., Navid, F., Schwarz, A., Johnson, D.A., Johnson, J.A. and Werner, S. (2010) Nrf2 establishes a glutathione-mediated gradient of UVB cytoprotection in the epidermis. Genes Dev. 24, 1045-1058
195. auf dem Keller, U., Huber, M., Beyer, T.A., Kumin, A., Siemes, C., Braun, S., Bugnon, P., Mitropoulos, V., Johnson, D.A., Johnson, J.A. et al. (2006) Nrf transcription factors in keratinocytes are essential for skin tumor prevention but not for wound healing. Mol. Cell. Biol. 26, 3773-3784
196. Ohta, T., Iijima, K., Miyamoto, M., Nakahara, I., Tanaka, H., Ohtsuji, M., Suzuki, T., Kobayashi, A., Yokota, J., Sakiyama, T. et al. (2008) Loss of Keap1 function activates Nrf2 and provides advantages for lung cancer cell growth. Cancer Res. 68, 1303-1309
197. DeNicola, G.M., Karreth, F.A., Humpton, T.J., Gopinathan, A., Wei, C., Frese, K., Mangal, D., Yu, K.H., Yeo, C.J., Calhoun, E.S. et al. (2011) Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature 475, 106-109
198. Kensler, T.W. and Wakabayashi, N. (2010) Nrf2: friend or foe for chemoprevention? Carcinogenesis 31, 90-99
199. Satoh, H., Moriguchi, T., Takai, J., Ebina, M. and Yamamoto, M. (2013) Nrf2 prevents initiation but accelerates progression through the Kras signaling pathway during lung carcinogenesis. Cancer Res. 73, 4158-4168
200. Moon, E.J. and Giaccia, A. (2015) Dual roles of NRF2 in tumor prevention and progression: possible implications in cancer treatment. Free Radical Biol. Med. 79, 292-299
201. Zheng, H., Fu, J., Xue, P., Zhao, R., Dong, J., Liu, D., Yamamoto, M., Tong, Q., Teng, W., Qu, W. et al. (2015) CNC-bZIP protein Nrf1-dependent regulation of glucose-stimulated insulin secretion. Antioxid. Redox Signal. 22, 819-831
202. Cullinan, S.B. and Diehl, J.A. (2006) Coordination of ER and oxidative stress signaling: the PERK/Nrf2 signaling pathway. Int. J. Biochem. Cell Biol. 38, 317-332
203. Digaleh, H., Kiaei, M. and Khodagholi, F. (2013) Nrf2 and Nrf1 signaling and ER stress crosstalk: implication for proteasomal degradation and autophagy. Cell. Mol. Life Sci. 70, 4681-4694
204. Chakravarthi, S., Jessop, C.E. and Bulleid, N.J. (2006) The role of glutathione in disulphide bond formation and endoplasmic-reticulum-generated oxidative stress. EMBO Rep. 7, 271-275
205. Cribb, A.E., Peyrou, M., Muruganandan, S. and Schneider, L. (2005) The endoplasmic reticulum in xenobiotic toxicity. Drug Metab. Rev. 37, 405-442
206. Sitia, R. and Braakman, I. (2003) Quality control in the endoplasmic reticulum protein factory. Nature 426, 891-894
207. Pearse, B.R. and Hebert, D.N. (2006) Cotranslocational degradation: utilitarianism in the ER stress response. Mol. Cell 23, 773-775
208. Schroder, M. and Kaufman, R.J. (2005) The mammalian unfolded protein response. Annu. Rev. Biochem. 74, 739-789
209. Choe, K.P. and Leung, C.K. (2013) SKN-1/Nrf, a new unfolded protein response factor? PLoS Genet 9, e1003827
210. Cullinan, S.B., Zhang, D., Hannink, M., Arvisais, E., Kaufman, R.J. and Diehl, J.A. (2003) Nrf2 is a direct PERK substrate and effector of PERK-dependent cell survival. Mol. Cell. Biol. 23, 7198-7209
211. Cullinan, S.B. and Diehl, J.A. (2004) PERK-dependent activation of Nrf2 contributes to redox homeostasis and cell survival following endoplasmic reticulum stress. J. Biol. Chem. 279, 20108-20117
212. Zhang, Y., Nicholatos, J., Dreier, J.R., Ricoult, S.J., Widenmaier, S.B., Hotamisligil, G.S., Kwiatkowski, D.J. and Manning, B.D. (2014) Coordinated regulation of protein synthesis and degradation by mTORC1. Nature 513, 440-443
213. Ye, J., Rawson, R.B., Komuro, R., Chen, X., Dave, U.P., Prywes, R., Brown, M.S. and Goldstein, J.L. (2000) ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol. Cell 6, 1355-1364
214. Wang, Q., Mora-Jensen, H., Weniger, M.A., Perez-Galan, P., Wolford, C., Hai, T., Ron, D., Chen, W., Trenkle, W., Wiestner, A. et al. (2009) ERAD inhibitors integrate ER stress with an epigenetic mechanism to activate BH3-only protein NOXA in cancer cells. Proc. Natl. Acad. Sci. U.S.A. 106, 2200-2205
215. Wouters, B.G. and Koritzinsky, M. (2008) Hypoxia signalling through mTOR and the unfolded protein response in cancer. Nat. Rev. Cancer 8, 851-864
216. Scriven, P., Brown, N.J., Pockley, A.G. and Wyld, L. (2007) The unfolded protein response and cancer: a brighter future unfolding? J. Mol. Med. 85, 331-341
217. Hotamisligil, G.S. (2010) Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell 140, 900-917
218. Wang, X., Sato, R., Brown, M.S., Hua, X. and Goldstein, J.L. (1994) SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis. Cell 77, 53-62
219. Sakai, J., Duncan, E.A., Rawson, R.B., Hua, X., Brown, M.S. and Goldstein, J.L. (1996) Sterol-regulated release of SREBP-2 from cell membranes requires two sequential cleavages, one within a transmembrane segment. Cell 85, 1037-1046
220. Brown, M.S. and Goldstein, J.L. (1997) The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell 89, 331-340
221. Balch, W.E., Morimoto, R.I., Dillin, A. and Kelly, J.W. (2008) Adapting proteostasis for disease intervention. Science 319, 916-919
222. Powers, E.T. and Balch, W.E. (2013) Diversity in the origins of proteostasis networks: a driver for protein function in evolution. Nat. Rev. Mol. Cell Biol. 14, 237-248
223. van Oosten-Hawle, P. and Morimoto, R.I. (2014) Organismal proteostasis: role of cell-nonautonomous regulation and transcellular chaperone signaling. Genes Dev. 28, 1533-1543
224. Tsakiri, E.N., Sykiotis, G.P., Papassideri, I.S., Terpos, E., Dimopoulos, M.A., Gorgoulis, V.G., Bohmann, D. and Trougakos, I.P. (2013) Proteasome dysfunction in Drosophila signals to an Nrf2-dependent regulatory circuit aiming to restore proteostasis and prevent premature aging. Aging Cell 12, 802-813
225. Pickering, A.M., Staab, T.A., Tower, J., Sieburth, D. and Davies, K.J. (2013) A conserved role for the 20S proteasome and Nrf2 transcription factor in oxidative stress adaptation in mammals, Caenorhabditis elegans and Drosophila melanogaster. J. Exp. Biol. 216, 543-553
226. Li, X., Matilainen, O., Jin, C., Glover-Cutter, K.M., Holmberg, C.I. and Blackwell, T.K. (2011) Specific SKN-1/Nrf stress responses to perturbations in translation elongation and proteasome activity. PLoS Genet. 7, e1002119
227. Couve, A. and Hetz, C. (2014) RESETing ER proteostasis: selective stress pathway hidden in the secretory route. EMBO J. 33, 2444-2446
228. Chondrogianni, N., Georgila, K., Kourtis, N., Tavernarakis, N.Gonos, E.S. (2015)Chondrogianni, N., Georgila, K., Kourtis, N., Tavernarakis, N. and Gonos, E.S. (2015)
229. 20S proteasome activation promotes life span extension and resistance to proteotoxicity in Caenorhabditis elegans. FASEB J. 29, 611-622
230. Mannhaupt, G., Schnall, R., Karpov, V., Vetter, I. and Feldmann, H. (1999) Rpn4p acts as a transcription factor by binding to PACE, a nonamer box found upstream of 26S proteasomal and other genes in yeast. FEBS Lett. 450, 27-34
231. Dohmen, R.J., Willers, I. and Marques, A.J. (2007) Biting the hand that feeds: Rpn4-dependent feedback regulation of proteasome function. Biochim. Biophys. Acta 1773, 1599-1604
232. Mitsiades, N., Mitsiades, C.S., Poulaki, V., Chauhan, D., Fanourakis, G., Gu, X., Bailey, C., Joseph, M., Libermann, T.A., Treon, S.P. et al. (2002) Molecular sequelae of proteasome inhibition in human multiple myeloma cells. Proc. Natl. Acad. Sci. U.S.A. 99, 14374-14379
233. Meiners, S., Heyken, D., Weller, A., Ludwig, A., Stangl, K., Kloetzel, P.M. and Kruger, E. (2003) Inhibition of proteasome activity induces concerted expression of proteasome genes and de novo formation of Mammalian proteasomes. J. Biol. Chem. 278, 21517-21525
234. Lundgren, J., Masson, P., Mirzaei, Z. and Young, P. (2005) Identification and characterization of a Drosophila proteasome regulatory network. Mol. Cell. Biol. 25, 4662-4675
235. Hirotsu, Y., Hataya, N., Katsuoka, F. and Yamamoto, M. (2012) NF-E2-related factor 1 (Nrf1) serves as a novel regulator of hepatic lipid metabolism through regulation of the Lipin1 and PGC-1β genes. Mol. Cell. Biol. 32, 2760-2770
236. Balasubramanian, S., Kanade, S., Han, B. and Eckert, R.L. (2012) A proteasome inhibitor-stimulated Nrf1 protein-dependent compensatory increase in proteasome subunit gene expression reduces polycomb group protein level. J. Biol. Chem. 287, 36179-36189
237. Enenkel, C., Lehmann, A. and Kloetzel, P.M. (1998) Subcellular distribution of proteasomes implicates a major location of protein degradation in the nuclear envelope-ER network in yeast. EMBO J. 17, 6144-6154
238. Brooks, P., Fuertes, G., Murray, R.Z., Bose, S., Knecht, E., Rechsteiner, M.C., Hendil, K.B., Tanaka, K., Dyson, J. and Rivett, J. (2000) Subcellular localization of proteasomes and their regulatory complexes in mammalian cells. Biochem. J. 346, 155-161
239. Russell, S.J., Steger, K.A. and Johnston, S.A. (1999) Subcellular localization, stoichiometry, and protein levels of 26 S proteasome subunits in yeast. J. Biol. Chem. 274, 21943-21952
240. Fabre, B., Lambour, T., Delobel, J., Amalric, F., Monsarrat, B., Burlet-Schiltz, O. and Bousquet-Dubouch, M.P. (2013) Subcellular distribution and dynamics of active proteasome complexes unraveled by a workflow combining in vivo complex cross-linking and quantitative proteomics. Mol. Cell. Proteomics 12, 687-699
241. Kahn, N.W., Rea, S.L., Moyle, S., Kell, A. and Johnson, T.E. (2008) Proteasomal dysfunction activates the transcription factor SKN-1 and produces a selective oxidative-stress response in Caenorhabditis elegans. Biochem. J. 409, 205-213
242. Holness, M.J., Bulmer, K., Gibbons, G.F. and Sugden, M.C. (2002) Up-regulation of pyruvate dehydrogenase kinase isoform 4 (PDK4) protein expression in oxidative skeletal muscle does not require the obligatory participation of peroxisome-proliferator-activated receptor α (PPARα). Biochem. J. 366, 839-846
243. Ip, E., Farrell, G.C., Robertson, G., Hall, P., Kirsch, R. and Leclercq, I. (2003) Central role of PPARα-dependent hepatic lipid turnover in dietary steatohepatitis in mice. Hepatology 38, 123-132
244. Peterfy, M., Phan, J., Xu, P. and Reue, K. (2001) Lipodystrophy in the fld mouse results from mutation of a new gene encoding a nuclear protein, lipin. Nat. Genet. 27, 121-124
245. Finck, B.N., Gropler, M.C., Chen, Z., Leone, T.C., Croce, M.A., Harris, T.E., Lawrence, Jr, J.C. and Kelly, D.P. (2006) Lipin 1 is an inducible amplifier of the hepatic PGC-1α/PPARα regulatory pathway. Cell Metab. 4, 199-210
246. Kelly, D.P. and Scarpulla, R.C. (2004) Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev. 18, 357-368
247. Speliotes, E.K., Willer, C.J., Berndt, S.I., Monda, K.L., Thorleifsson, G., Jackson, A.U., Lango Allen, H., Lindgren, C.M., Luan, J., Magi, R. et al. (2010) Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat. Genet. 42, 937-948
248. Hirotsu, Y., Higashi, C., Fukutomi, T., Katsuoka, F., Tsujita, T., Yagishita, Y., Matsuyama, Y., Motohashi, H., Uruno, A. and Yamamoto, M. (2014) Transcription factor NF-E2-related factor 1 impairs glucose metabolism in mice. Genes Cells 19, 650-665
249. Tanikawa, J., Yasukawa, T., Enari, M., Ogata, K., Nishimura, Y., Ishii, S. and Sarai, A. (1993) Recognition of specific DNA sequences by the c-myb protooncogene product: role of three repeat units in the DNA-binding domain. Proc. Natl. Acad. Sci. U.S.A. 90, 9320-9324
250. Uruno, A., Furusawa, Y., Yagishita, Y., Fukutomi, T., Muramatsu, H., Negishi, T., Sugawara, A., Kensler, T.W. and Yamamoto, M. (2013) The Keap1-Nrf2 system prevents onset of diabetes mellitus. Mol. Cell. Biol. 33, 2996-3010
251. Yagishita, Y., Fukutomi, T., Sugawara, A., Kawamura, H., Takahashi, T., Pi, J., Uruno, A. and Yamamoto, M. (2014) Nrf2 protects pancreatic β-cells from oxidative and nitrosative stress in diabetic model mice. Diabetes 63, 605-618
252. Buettner, C. (2012) Is hyperinsulinemia required to develop overeating-induced obesity? Cell Metab. 16, 691-692
253. Corkey, B.E. (2012) Banting Lecture 2011. Hyperinsulinemia: cause or consequence? Diabetes 61, 4-13
254. Levine, A.J. and Puzio-Kuter, A.M. (2010) The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes. Science 330, 1340-1344
255. Bugno, M., Daniel, M., Chepelev, N.L. and Willmore, W.G. (2015) Changing gears in Nrf1 research, from mechanisms of regulation to its role in disease and prevention. Biochim. Biophys. Acta 1849, 1260-1276
256. Brown, M.S., Ye, J., Rawson, R.B. and Goldstein, J.L. (2000) Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans. Cell 100, 391-398
257. Webster, B.M. and Lusk, C.P. (2016) Border safety: quality control at the nuclear envelope. Trends Cell Biol. 26, 29-39
258. Koenig, P.A. and Ploegh, H.L. (2014) Protein quality control in the endoplasmic reticulum. F1000Prime Rep. 6, 49
259. Ruggiano, A., Foresti, O. and Carvalho, P. (2014) Quality control: ER-associated degradation: protein quality control and beyond. J. Cell Biol. 204, 869-879
260. Chowdhury, M. and Enenkel, C. (2015) Intracellular dynamics of the ubiquitin-proteasome-system. F1000Res. 4, 367
261. Boban, M. and Foisner, R. (2016) Degradation-mediated protein quality control at the inner nuclear membrane. Nucleus, doi:10.1080/19491034.19492016.11139273
262. Gamerdinger, M., Hanebuth, M.A., Frickey, T. and Deuerling, E. (2015) The principle of antagonism ensures protein targeting specificity at the endoplasmic reticulum. Science 348, 201-207
263. Khmelinskii, A., Blaszczak, E., Pantazopoulou, M., Fischer, B., Omnus, D.J., Le Dez, G., Brossard, A., Gunnarsson, A., Barry, J.D., Meurer, M. et al. (2014) Protein quality control at the inner nuclear membrane. Nature 516, 410-413
264. Foresti, O., Rodriguez-Vaello, V., Funaya, C. and Carvalho, P. (2014) Quality control of inner nuclear membrane proteins by the Asi complex. Science 346, 751-755
265. Schuck, S. and Simons, K. (2004) Polarized sorting in epithelial cells: raft clustering and the biogenesis of the apical membrane. J. Cell Sci. 117, 5955-5964
266. Voeltz, G.K., Rolls, M.M. and Rapoport, T.A. (2002) Structural organization of the endoplasmic reticulum. EMBO Rep. 3, 944-950
267. Allen, J.A., Halverson-Tamboli, R.A. and Rasenick, M.M. (2007) Lipid raft microdomains and neurotransmitter signalling. Nat. Rev. Neurosci. 8, 128-140
268. Rajendran, L. and Simons, K. (2005) Lipid rafts and membrane dynamics. J. Cell Sci. 118, 1099-1102
269. Parton, R.G. and Simons, K. (2007) The multiple faces of caveolae. Nat. Rev. Mol. Cell Biol. 8, 185-194
270. Lusk, C.P., Blobel, G. and King, M.C. (2007) Highway to the inner nuclear membrane: rules for the road. Nat. Rev. Mol. Cell Biol. 8, 414-420
271. Antonin, W., Ungricht, R. and Kutay, U. (2011) Traversing the NPC along the pore membrane: targeting of membrane proteins to the INM. Nucleus 2, 87-91
272. Burns, L.T. and Wente, S.R. (2012) Trafficking to uncharted territory of the nuclear envelope. Curr. Opin. Cell Biol. 24, 341-349
273. Zuleger, N., Kerr, A.R. and Schirmer, E.C. (2012) Many mechanisms, one entrance: membrane protein translocation into the nucleus. Cell. Mol. Life Sci. 69, 2205-2216
274. Laba, J.K., Steen, A. and Veenhoff, L.M. (2014) Traffic to the inner membrane of the nuclear envelope. Curr. Opin. Cell Biol. 28, 36-45
275. Ungricht, R., Klann, M., Horvath, P. and Kutay, U. (2015) Diffusion and retention are major determinants of protein targeting to the inner nuclear membrane. J. Cell Biol. 209, 687-703
276. Ungricht, R. and Kutay, U. (2015) Establishment of NE asymmetry-targeting of membrane proteins to the inner nuclear membrane. Curr. Opin. Cell Biol. 34, 135-141
277. Brown, R.S., Zhao, C., Chase, A.R., Wang, J. and Schlieker, C. (2014) The mechanism of Torsin ATPase activation. Proc. Natl. Acad. Sci. U.S.A. 111, E4822-E4831
278. Sosa, B.A., Demircioglu, F.E., Chen, J.Z., Ingram, J., Ploegh, H.L. and Schwartz, T.U. (2014) How lamina-associated polypeptide 1 (LAP1) activates Torsin. eLife 3, e03239
279. Mattaj, I.W. (2004) Sorting out the nuclear envelope from the endoplasmic reticulum. Nat. Rev. Mol. Cell Biol. 5, 65-69
280. Furth, N., Gertman, O., Shiber, A., Alfassy, O.S., Cohen, I., Rosenberg, M.M., Doron, N.K., Friedler, A. and Ravid, T. (2011) Exposure of bipartite hydrophobic signal triggers nuclear quality control of Ndc10 at the endoplasmic reticulum/nuclear envelope. Mol. Biol. Cell 22, 4726-4739
281. Kupke, T., Di Cecco, L., Muller, H.M., Neuner, A., Adolf, F., Wieland, F., Nickel, W. and Schiebel, E. (2011) Targeting of Nbp1 to the inner nuclear membrane is essential for spindle pole body duplication. EMBO J. 30, 3337-3352
282. Boban, M., Pantazopoulou, M., Schick, A., Ljungdahl, P.O. and Foisner, R. (2014) A nuclear ubiquitin-proteasome pathway targets the inner nuclear membrane protein Asi2 for degradation. J. Cell Sci. 127, 3603-3613
283. Kaganovich, D., Kopito, R. and Frydman, J. (2008) Misfolded proteins partition between two distinct quality control compartments. Nature 454, 1088-1095
284. Weberruss, M.H., Savulescu, A.F., Jando, J., Bissinger, T., Harel, A., Glickman, M.H. and Enenkel, C. (2013) Blm10 facilitates nuclear import of proteasome core particles. EMBO J. 32, 2697-2707
285. Heessen, S. and Fornerod, M. (2007) The inner nuclear envelope as a transcription factor resting place. EMBO Rep. 8, 914-919
286. Ivorra, C., Kubicek, M., Gonzalez, J.M., Sanz-Gonzalez, S.M., Alvarez-Barrientos, A., O'Connor, J.E., Burke, B. and Andres, V. (2006) A mechanism of AP-1 suppression through interaction of c-Fos with lamin A/C. Genes Dev. 20, 307-320
287. Capanni, C., Mattioli, E., Columbaro, M., Lucarelli, E., Parnaik, V.K., Novelli, G., Wehnert, M., Cenni, V., Maraldi, N.M., Squarzoni, S. et al. (2005) Altered pre-lamin A processing is a common mechanism leading to lipodystrophy. Hum. Mol. Genet. 14, 1489-1502
288. Hu, Q., Kwon, Y.S., Nunez, E., Cardamone, M.D., Hutt, K.R., Ohgi, K.A., Garcia-Bassets, I., Rose, D.W., Glass, C.K., Rosenfeld, M.G. et al. (2008) Enhancing nuclear receptor-induced transcription requires nuclear motor and LSD1-dependent gene networking in interchromatin granules. Proc. Natl. Acad. Sci. U.S.A. 105, 19199-19204
289. Hansen, J.M., Go, Y.M. and Jones, D.P. (2006) Nuclear and mitochondrial compartmentation of oxidative stress and redox signaling. Annu. Rev. Pharmacol. Toxicol. 46, 215-234
290. L'Honore, A., Commere, P.H., Ouimette, J.F., Montarras, D., Drouin, J. and Buckingham, M. (2014) Redox regulation by Pitx2 and Pitx3 is critical for fetal myogenesis. Dev. Cell 29, 392-405
291. Molofsky, A.V., Glasgow, S.M., Chaboub, L.S., Tsai, H.H., Murnen, A.T., Kelley, K.W., Fancy, S.P., Yuen, T.J., Madireddy, L., Baranzini, S. et al. (2013) Expression profiling of Aldh1l1-precursors in the developing spinal cord reveals glial lineage-specific genes and direct Sox9-Nfe2l1 interactions. Glia 61, 1518-1532
292. Berg, D.T., Gupta, A., Richardson, M.A., O'Brien, L.A., Calnek, D. and Grinnell, B.W. (2007) Negative regulation of inducible nitric-oxide synthase expression mediated through transforming growth factor-β-dependent modulation of transcription factor TCF11. J. Biol. Chem. 282, 36837-36844
293. Dhakshinamoorthy, S. and Jaiswal, A.K. (2000) Small maf (MafG and MafK) proteins negatively regulate antioxidant response element-mediated expression and antioxidant induction of the NAD(P)H:quinone oxidoreductase1 gene. J. Biol. Chem. 275, 40134-40141
294. Eferl, R., Ricci, R., Kenner, L., Zenz, R., David, J.P., Rath, M. and Wagner, E.F. (2003) Liver tumor development. c-Jun antagonizes the proapoptotic activity of p53. Cell 112, 181-192
295. Weitzman, J.B., Fiette, L., Matsuo, K. and Yaniv, M. (2000) JunD protects cells from p53-dependent senescence and apoptosis. Mol. Cell 6, 1109-1119
296. von Heijne, G. (1989) Control of topology and mode of assembly of a polytopic membrane protein by positively charged residues. Nature 341, 456-458
297. von Heijne, G. and Gavel, Y. (1988) Topogenic signals in integral membrane proteins. Eur.J.Biochem.174, 671-678
298. Choi, H., Jackson, N.L., Shaw, D.R., Emanuel, P.D., Liu, Y.L., Tousson, A., Meng, Z. and Blume, S.W. (2008) mrtl-A translation/localization regulatory protein encoded within the human c-myc locus and distributed throughout the endoplasmic and nucleoplasmic reticular network. J. Cell Biochem. 105, 1092-1108
299. Wethmar, K., Smink, J.J. and Leutz, A. (2010) Upstream open reading frames: molecular switches in (patho)physiology. BioEssays 32, 885-893
300. Mielnicki, L.M., Hughes, R.G., Chevray, P.M. and Pruitt, S.C. (1996) Mutated Atf4 suppresses c-Ha-ras oncogene transcript levels and cellular transformation in NIH3T3 fibroblasts. Biochem. Biophys. Res. Commun. 228, 586-595
301. Kokot, A., Metze, D., Mouchet, N., Galibert, M.D., Schiller, M., Luger, T.A. and Bohm, M. (2009) α-Melanocyte-stimulating hormone counteracts the suppressive effect of UVB on Nrf2 and Nrf-dependent gene expression in human skin. Endocrinology 150, 3197-3206
302. Sato, R., Yang, J., Wang, X., Evans, M.J., Ho, Y.K., Goldstein, J.L. and Brown, M.S. (1994) Assignment of the membrane attachment, DNA binding, and transcriptional activation domains of sterol regulatory element-binding protein-1 (SREBP-1). J. Biol. Chem. 269, 17267-17273