Post-translational modification of transcription factors: Mechanisms and potential therapeutic interventions

Current Molecular Pharmacology

Volumn 6, Issue 3, 2013, Pages 173-182

  Planey, Sonia L ^a   Kumar, Raj ^a   Arnott, John A ^a  

^a Geisinger Health Geisinger Commonwealth School of Medicine   (United States)

Author keywords

Drug development; Gene regulation; Post translational modifications; Transcription factors

Indexed keywords

ARGININE; CYSTEINE; DNA; HISTIDINE; HISTONE DEACETYLASE; HISTONE DEACETYLASE INHIBITOR; LYSINE; METHIONINE; PHOSPHATASE; PROLINE; PROTEIN KINASE; PROTEIN P53; REACTIVE OXYGEN METABOLITE; SERINE; TAMOXIFEN; THREONINE; TRANSCRIPTION FACTOR; TYROSINE;

ACETYLATION; ARTICLE; CELLULAR DISTRIBUTION; CONFORMATIONAL TRANSITION; DNA BINDING MOTIF; DNA HISTONE INTERACTION; DRUG DESIGN; DRUG RESPONSE; ENZYME SPECIFICITY; GENE ACTIVATION; GENETIC TRANSCRIPTION; HUMAN; OXIDATION; PATHOPHYSIOLOGY; PLEIOTROPY; PRIORITY JOURNAL; PROGNOSIS; PROTEIN DEGRADATION; PROTEIN DNA INTERACTION; PROTEIN EXPRESSION; PROTEIN INTERACTION; PROTEIN LOCALIZATION; PROTEIN METHYLATION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; PROTEIN PROTEIN INTERACTION; PROTEIN STABILITY; REGULATORY MECHANISM; SUMOYLATION; TRANSCRIPTION INITIATION; TRANSCRIPTION REGULATION; UBIQUITINATION; ANIMAL; CHEMISTRY; DRUG DELIVERY SYSTEM; DRUG DEVELOPMENT; DRUG EFFECTS; METABOLISM; PROCEDURES;

ANIMALS; DRUG DELIVERY SYSTEMS; DRUG DISCOVERY; HUMANS; PROTEIN PROCESSING, POST-TRANSLATIONAL; TRANSCRIPTION FACTORS;

EID: 84901265220     PISSN: 18744672     EISSN: 18744702     Source Type: Journal    
DOI: 10.2174/1874467207666140307124241     Document Type: Article

References (130)

1. Hurst, L.D.; Pal, C.; Lercher, M.J. The evolutionary dynamics of eukaryotic gene order. Nat. Rev. Genet., 2004, 5(4), 299-310.
2. Lee, J.M.; Sonnhammer, E.L. Genomic gene clustering analysis of pathways in eukaryotes. Genome Res., 2003, 13(5), 875-882.
3. Reddy, P.M.; Stamatoyannopoulos, G.; Papayannopoulou, T.; Shen, C.K. Genomic footprinting and sequencing of human betaglobin locus. Tissue specificity and cell line artifact. J. Biol. Chem., 1994, 269(11), 8287-8295.
4. Remenyi, A.; Scholer, H.R.; Wilmanns, M. Combinatorial control of gene expression. Nat. Struct. Mol. Biol., 2004, 11(9), 812-815.
5. Sproul, D.; Gilbert, N.; Bickmore, W.A. The role of chromatin structure in regulating the expression of clustered genes. Nat. Rev. Genet., 2005, 6(10), 775-781.
6. Li, B.; Carey, M.; Workman, J.L., The role of chromatin during transcription. Cell, 2007, 128(4), 707-719.
7. Pugh, B.F. Control of gene expression through regulation of the TATA-binding protein. Gene, 2000, 255(1), 1-14.
8. Garza, A.M.; Khan, S.H.; Kumar, R. Site-specific phosphorylation induces functionally active conformation in the intrinsically disordered N-terminal activation function (AF1) domain of the glucocorticoid receptor. Mol. Cell. Biol., 2010, 30(1), 220-230.
9. Geng, H.; Liu, Q.; Xue, C.; David, L.L.; Beer, T.M.; Thomas, G.V.; Dai, M.S.; Qian, D. Z. HIF1alpha protein stability is increased by acetylation at lysine 709. J Biol Chem 2012, 287(42), 35496-35505.
10. Le Romancer, M.; Poulard, C.; Cohen, P.; Sentis, S.; Renoir, J.M.; Corbo, L. Cracking the estrogen receptor's posttranslational code in breast tumors. Endocr. Rev., 2011, 32(5), 597-622.
11. Ma, A.; Malynn, B.A. A20: linking a complex regulator of ubiquitylation to immunity and human disease. Nat. Rev. Immunol., 2012, 12(11), 774-785.
12. Rytinki, M.; Kaikkonen, S.; Sutinen, P.; Paakinaho, V.; Rahkama, V.; Palvimo, J.J. Dynamic SUMOylation is linked to the activity cycles of androgen receptor in the cell nucleus. Mol. Cell. Biol., 2012, 32(20), 4195-4205.
13. Venkatesh, S.; Smolle, M.; Li, H.; Gogol, M.M.; Saint, M.; Kumar, S.; Natarajan, K.; Workman, J.L. Set2 methylation of histone H3 lysine 36 suppresses histone exchange on transcribed genes. Nature, 2012, 489(7416), 452-455.
14. Hedrick, S.M.; Hess Michelini, R.; Doedens, A.L.; Goldrath, A.W.; Stone, E.L. FOXO transcription factors throughout T cell biology. Nat. Rev. Immunol., 2012, 12(9), 649-661.
15. Ke, P.Y.; Chen, S.S. Activation of the unfolded protein response and autophagy after hepatitis C virus infection suppresses innate antiviral immunity in vitro. J. Clin. Invest., 2011, 121(1), 37-56.
16. Rousset, R.; Desbois, C.; Bantignies, F.; Jalinot, P. Effects on NFkappa B1/p105 processing of the interaction between the HTLV-1 transactivator Tax and the proteasome. Nature, 1996, 381(6580), 328-331.
17. Cohen, B.E.; Lee, G.; Arispe, N.; Pollard, H.B. Cyclic 3'-5'-adenosine monophosphate binds to annexin I and regulates calcium-dependent membrane aggregation and ion channel activity. FEBS Lett., 1995, 377(3), 444-450.
18. Manning, G.; Plowman, G.D.; Hunter, T.; Sudarsanam, S. Evolution of protein kinase signaling from yeast to man. Trends Biochem. Sci., 2002, 27(10), 514-520.
19. Manning, G.; Whyte, D.B.; Martinez, R.; Hunter, T.; Sudarsanam, S. The protein kinase complement of the human genome. Science, 2002, 298(5600), 1912-1934.
20. Bruce, D.L.; Sapkota, G.P. Phosphatases in SMAD regulation. FEBS Lett., 2012, 586(14), 1897-1905.
21. Li, S.; Shang, Y. Regulation of SRC family coactivators by posttranslational modifications. Cell Signal., 2007, 19(6), 1101-1112.
22. Whitmarsh, A.J. Regulation of gene transcription by mitogenactivated protein kinase signaling pathways. Biochim. Biophys. Acta, 2007, 1773(8), 1285-1298.
23. Hunter, T. Protein kinases and phosphatases: the yin and yang of protein phosphorylation and signaling. Cell, 1995, 80(2), 225-236.
24. Denu, J.M.; Stuckey, J.A.; Saper, M.A.; Dixon, J.E. Form and function in protein dephosphorylation. Cell, 1996, 87(3), 361-364.
25. Ciesla, J.; Fraczyk, T.; Rode, W. Phosphorylation of basic amino acid residues in proteins: important but easily missed. Acta Biochim. Pol., 2011, 58(2), 137-148.
26. Hunter, T.; Karin, M. The regulation of transcription by phosphorylation. Cell, 1992, 70(3), 375-387.
27. Karin, M.; Hunter, T. Transcriptional control by protein phosphorylation: signal transmission from the cell surface to the nucleus. Curr. Biol., 1995, 5(7), 747-757.
28. Whitmarsh, A.J.; Davis, R.J. Regulation of transcription factor function by phosphorylation. Cell Mol. Life Sci., 2000, 57(8-9), 1172-1183.
29. Wieczorek, M.; Ginter, T.; Brand, P.; Heinzel, T.; Kramer, O.H. Acetylation modulates the STAT signaling code. Cytokine Growth Factor Rev., 2012, 23(6), 293-305.
30. Harrison, D.A. The Jak/STAT pathway. Cold Spring Harb. Perspect. Biol., 2012, 4(3), pii: a011205.
31. Kiu, H.; Nicholson, S.E. Biology and significance of the JAK/STAT signalling pathways. Growth Factors, 2012, 30(2), 88-106.
32. Mertens, C.; Darnell, J.E. Jr. SnapShot: JAK-STAT signaling. Cell 2007, 131(3), 612.
33. Yang, J.; Stark, G.R. Roles of unphosphorylated STATs in signaling. Cell Res., 2008, 18(4), 443-451.
34. Ihle, J.N. The Stat family in cytokine signaling. Curr. Opin. Cell. Biol., 2001, 13(2), 211-217.
35. Liu, F.; Hata, A.; Baker, J.C.; Doody, J.; Carcamo, J.; Harland, R.M.; Massague, J. A human Mad protein acting as a BMPregulated transcriptional activator. Nature, 1996, 381(6583), 620-623.
36. Gu, L.; Zhu, Y.J.; Yang, X.; Guo, Z.J.; Xu, W.B.; Tian, X.L. Effect of TGF-beta/Smad signaling pathway on lung myofibroblast differentiation. Acta Pharmacol. Sin., 2007, 28(3), 382-391.
37. Shaywitz, A.J.; Greenberg, M.E. CREB: a stimulus-induced transcription factor activated by a diverse array of extracellular signals. Annu. Rev. Biochem., 1999, 68, 821-861.
38. De Cesare, D.; Fimia, G.M.; Sassone-Corsi, P. Signaling routes to CREM and CREB: plasticity in transcriptional activation. Trends Biochem. Sci., 1999, 24(7), 281-285.
39. Workman, J.L.; Kingston, R.E. Alteration of nucleosome structure as a mechanism of transcriptional regulation. Annu. Rev. Biochem., 1998, 67, 545-579.
40. Spange, S.; Wagner, T.; Heinzel, T.; Kramer, O.H. Acetylation of non-histone proteins modulates cellular signalling at multiple levels. Int. J. Biochem. Cell Biol., 2009, 41(1), 185-198.
41. Kouzarides, T. Acetylation: a regulatory modification to rival phosphorylation? EMBO J., 2000, 19(6), 1176-1179.
42. Yang, X.J.; Seto, E. Lysine acetylation: codified crosstalk with other posttranslational modifications. Mol. Cell, 2008, 31(4), 449-461.
43. Kim, M.Y.; Bae, J.S.; Kim, T.H.; Park, J.M.; Ahn, Y.H. Role of transcription factor modifications in the pathogenesis of insulin resistance. Exp. Diabetes Res., 2012, 2012, 716425.
44. van der Heide, L.P.; Smidt, M.P. Regulation of FoxO activity by CBP/p300-mediated acetylation. Trends Biochem. Sci., 2005, 30(2), 81-86.
45. Durrin, L.K.; Mann, R.K.; Kayne, P.S.; Grunstein, M. Yeast histone H4 N-terminal sequence is required for promoter activation in vivo. Cell, 1991, 65(6), 1023-1031.
46. Tootle, T.L.; Rebay, I. Post-translational modifications influence transcription factor activity: a view from the ETS superfamily. Bioessays, 2005, 27(3), 285-298.
47. Gu, W.; Roeder, R.G. Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell 1997, 90(4), 595-606.
48. Brooks, C.L.; Gu, W. The impact of acetylation and deacetylation on the p53 pathway. Protein Cell 2011, 2 (6), 456-462.
49. Li, A.G.; Piluso, L.G.; Cai, X.; Gadd, B.J.; Ladurner, A.G.; Liu, X. An acetylation switch in p53 mediates holo-TFIID recruitment. Mol. Cell, 2007, 28(3), 408-421.
50. Sykes, S.M.; Mellert, H.S.; Holbert, M.A.; Li, K.; Marmorstein, R.; Lane, W.S.; McMahon, S.B. Acetylation of the p53 DNA-binding domain regulates apoptosis induction. Mol. Cell, 2006, 24(6), 841-851.
51. Tang, Y.; Luo, J.; Zhang, W.; Gu, W. Tip60-dependent acetylation of p53 modulates the decision between cell-cycle arrest and apoptosis. Mol. Cell, 2006, 24(6), 827-839.
52. Goodman, R.H.; Smolik, S. CBP/p300 in cell growth, transformation, and development. Genes Dev., 2000, 14(13), 1553-1577.
53. Tang, Y.; Zhao, W.; Chen, Y.; Zhao, Y.; Gu, W. Acetylation is indispensable for p53 activation. Cell, 2008, 133(4), 612-26.
54. Brooks, C.L.; Gu, W. p53 ubiquitination: Mdm2 and beyond. Mol. Cell, 2006, 21(3), 307-315.
55. Wang, X.; Taplick, J.; Geva, N.; Oren, M. Inhibition of p53 degradation by Mdm2 acetylation. FEBS Lett., 2004, 561(1-3), 195-201.
56. Benkirane, M.; Sardet, C.; Coux, O. Lessons from interconnected ubiquitylation and acetylation of p53: think metastable networks. Biochem. Soc. Trans., 2010, 38(Pt. 1), 98-103.
57. Luo, J.; Li, M.; Tang, Y.; Laszkowska, M.; Roeder, R.G.; Gu, W. Acetylation of p53 augments its site-specific DNA binding both in vitro and in vivo. Proc. Natl. Acad. Sci. USA, 2004, 101(8), 2259-2264.
58. Chang, H.M.; Paulson, M.; Holko, M.; Rice, C.M.; Williams, B.R.; Marie, I.; Levy, D.E. Induction of interferon-stimulated gene expression and antiviral responses require protein deacetylase activity. Proc. Natl. Acad. Sci. USA, 2004, 101(26), 9578-9583.
59. Klampfer, L.; Huang, J.; Swaby, L.A.; Augenlicht, L. Requirement of histone deacetylase activity for signaling by STAT1. J. Biol. Chem., 2004, 279(29), 30358-30368.
60. Nusinzon, I.; Horvath, C.M. Interferon-stimulated transcription and innate antiviral immunity require deacetylase activity and histone deacetylase 1. Proc. Natl. Acad. Sci. USA, 2003, 100(25), 14742-14747.
61. Kramer, O.H.; Baus, D.; Knauer, S.K.; Stein, S.; Jager, E.; Stauber, R.H.; Grez, M.; Pfitzner, E.; Heinzel, T. Acetylation of Stat1 modulates NF-kappaB activity. Genes Dev., 2006, 20(4), 473-485.
62. Wang, R.; Cherukuri, P.; Luo, J. Activation of Stat3 sequencespecific DNA binding and transcription by p300/CREB-binding protein-mediated acetylation. J. Biol. Chem., 2005, 280(12), 11528-11534.
63. Yuan, Z.L.; Guan, Y.J.; Chatterjee, D.; Chin, Y.E. Stat3 dimerization regulated by reversible acetylation of a single lysine residue. Science, 2005, 307(5707), 269-273.
64. Schubert, H.L.; Blumenthal, R.M.; Cheng, X. Many paths to methyltransfer: a chronicle of convergence. Trends Biochem. Sci., 2003, 28(6), 329-35.
65. Paro, R. Chromatin regulation. Formatting genetic text. Nature, 2000, 406(6796), 579-580.
66. Carr, S.M.; Munro, S.; La Thangue, N.B. Lysine methylation and the regulation of p53. Essays Biochem., 2012, 52, 79-92.
67. Lu, T.; Jackson, M.W.; Wang, B.; Yang, M.; Chance, M.R.; Miyagi, M.; Gudkov, A.V.; Stark, G.R. Regulation of NF-kappaB by NSD1/FBXL11-dependent reversible lysine methylation of p65. Proc. Natl. Acad. Sci. USA, 2010, 107(1), 46-51.
68. Yang, J.; Huang, J.; Dasgupta, M.; Sears, N.; Miyagi, M.; Wang, B.; Chance, M.R.; Chen, X.; Du, Y.; Wang, Y.; An, L.; Wang, Q.; Lu, T.; Zhang, X.; Wang, Z.; Stark, G.R. Reversible methylation of promoter-bound STAT3 by histone-modifying enzymes. Proc. Natl. Acad. Sci. USA, 2010, 107(50), 21499-21504.
69. Kontaki, H.; Talianidis, I. Lysine methylation regulates E2F1-induced cell death. Mol. Cell, 2010, 39(1), 152-160.
70. Calnan, D.R.; Webb, A.E.; White, J.L.; Stowe, T.R.; Goswami, T.; Shi, X.; Espejo, A.; Bedford, M.T.; Gozani, O.; Gygi, S.P.; Brunet, A. Methylation by Set9 modulates FoxO3 stability and transcriptional activity. Aging (Albany NY), 2012, 4(7), 462-479.
71. Subramanian, K.; Jia, D.; Kapoor-Vazirani, P.; Powell, D.R.; Collins, R.E.; Sharma, D.; Peng, J.; Cheng, X.; Vertino, P.M. Regulation of estrogen receptor alpha by the SET7 lysine methyltransferase. Mol. Cell, 2008, 30(3), 336-347.
72. Gamble, M.J.; Freedman, L.P. A coactivator code for transcription. Trends Biochem. Sci., 2002, 27(4), 165-167.
73. Chen, D.; Ma, H.; Hong, H.; Koh, S.S.; Huang, S.M.; Schurter, B.T.; Aswad, D.W.; Stallcup, M.R. Regulation of transcription by a protein methyltransferase. Science, 1999, 284(5423), 2174-2177.
74. Shen, E.C.; Henry, M.F.; Weiss, V.H.; Valentini, S.R.; Silver, P.A.; Lee, M.S. Arginine methylation facilitates the nuclear export of hnRNP proteins. Genes Dev., 1998, 12(5), 679-691.
75. Chuikov, S.; Kurash, J.K.; Wilson, J.R.; Xiao, B.; Justin, N.; Ivanov, G.S.; McKinney, K.; Tempst, P.; Prives, C.; Gamblin, S.J.; Barlev, N.A.; Reinberg, D. Regulation of p53 activity through lysine methylation. Nature, 2004, 432(7015), 353-360.
76. Huang, J.; Perez-Burgos, L.; Placek, B.J.; Sengupta, R.; Richter, M.; Dorsey, J.A.; Kubicek, S.; Opravil, S.; Jenuwein, T.; Berger, S.L. Repression of p53 activity by Smyd2-mediated methylation. Nature, 2006, 444(7119), 629-632.
77. Huang, J.; Sengupta, R.; Espejo, A.B.; Lee, M.G.; Dorsey, J.A.; Richter, M.; Opravil, S.; Shiekhattar, R.; Bedford, M.T.; Jenuwein, T.; Berger, S.L. p53 is regulated by the lysine demethylase LSD1. Nature, 2007, 449(7158), 105-108.
78. Shi, X.; Kachirskaia, I.; Yamaguchi, H.; West, L.E.; Wen, H.; Wang, E.W.; Dutta, S.; Appella, E.; Gozani, O. Modulation of p53 function by SET8-mediated methylation at lysine 382. Mol. Cell, 2007, 27(4), 636-646.
79. Huang, J.; Dorsey, J.; Chuikov, S.; Perez-Burgos, L.; Zhang, X.; Jenuwein, T.; Reinberg, D.; Berger, S. L., G9a and Glp methylate lysine 373 in the tumor suppressor p53. J. Biol. Chem., 2010, 285(13), 9636-9641.
80. Ivanov, G.S.; Ivanova, T.; Kurash, J.; Ivanov, A.; Chuikov, S.; Gizatullin, F.; Herrera-Medina, E.M.; Rauscher, F., 3rd; Reinberg, D.; Barlev, N.A. Methylation-acetylation interplay activates p53 in response to DNA damage. Mol. Cell. Biol., 2007, 27(19), 6756-6769.
81. Brunet, A.; Sweeney, L.B.; Sturgill, J.F.; Chua, K.F.; Greer, P.L.; Lin, Y.; Tran, H.; Ross, S.E.; Mostoslavsky, R.; Cohen, H.Y.; Hu, L.S.; Cheng, H.L.; Jedrychowski, M.P.; Gygi, S.P.; Sinclair, D.A.; Alt, F.W.; Greenberg, M.E. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science, 2004, 303(5666), 2011-2015.
82. Yamagata, K.; Daitoku, H.; Takahashi, Y.; Namiki, K.; Hisatake, K.; Kako, K.; Mukai, H.; Kasuya, Y.; Fukamizu, A. Arginine methylation of FOXO transcription factors inhibits their phosphorylation by Akt. Mol. Cell, 2008, 32(2), 221-231.
83. Lee, Y.H.; Stallcup, M.R. Minireview: protein arginine methylation of nonhistone proteins in transcriptional regulation. Mol. Endocrinol., 2009, 23(4), 425-433.
84. Chevillard-Briet, M.; Trouche, D.; Vandel, L. Control of CBP coactivating activity by arginine methylation. EMBO J., 2002, 21(20), 5457-5466.
85. Xu, W.; Chen, H.; Du, K.; Asahara, H.; Tini, M.; Emerson, B.M.; Montminy, M.; Evans, R.M. A transcriptional switch mediated by cofactor methylation. Science, 2001, 294(5551), 2507-2511.
86. Chen, D.; Huang, S.M.; Stallcup, M.R. Synergistic, p160 coactivator-dependent enhancement of estrogen receptor function by CARM1 and p300. J. Biol. Chem., 2000, 275(52), 40810-40816.
87. Gill, G. SUMO and ubiquitin in the nucleus: different functions, similar mechanisms? Genes Dev., 2004, 18(17), 2046-2059.
88. Glickman, M.H.; Ciechanover, A. The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol. Rev., 2002, 82(2), 373-428.
89. Muller, S.; Hoege, C.; Pyrowolakis, G.; Jentsch, S., SUMO, ubiquitin's mysterious cousin. Nat. Rev. Mol. Cell Biol., 2001, 2(3), 202-210.
90. Seeler, J.S.; Dejean, A. Nuclear and unclear functions of SUMO. Nat. Rev. Mol. Cell Biol., 2003, 4(9), 690-699.
91. Verger, A.; Perdomo, J.; Crossley, M. Modification with SUMO. A role in transcriptional regulation. EMBO Rep., 2003, 4(2), 137-142.
92. Conaway, R.C.; Brower, C.S.; Conaway, J.W. Emerging roles of ubiquitin in transcription regulation. Science, 2002, 296(5571), 1254-1258.
93. Ciechanover, A.; Orian, A.; Schwartz, A.L. Ubiquitin-mediated proteolysis: biological regulation via destruction. Bioessays, 2000, 22(5), 442-451.
94. Muratani, M.; Tansey, W.P. How the ubiquitin-proteasome system controls transcription. Nat. Rev. Mol. Cell. Biol., 2003, 4(3), 192-201.
95. Karin, M.; Ben-Neriah, Y. Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity. Annu. Rev. Immunol., 2000, 18, 621-663.
96. Kaiser, P.; Flick, K.; Wittenberg, C.; Reed, S.I. Regulation of transcription by ubiquitination without proteolysis: Cdc34/SCF(Met30)-mediated inactivation of the transcription factor Met4. Cell, 2000, 102(3), 303-314.
97. Gill, G. Post-translational modification by the small ubiquitinrelated modifier SUMO has big effects on transcription factor activity. Curr. Opin. Genet. Dev., 2003, 13(2), 108-113.
98. Lin, X.; Sun, B.; Liang, M.; Liang, Y.Y.; Gast, A.; Hildebrand, J.; Brunicardi, F.C.; Melchior, F.; Feng, X.H. Opposed regulation of corepressor CtBP by SUMOylation and PDZ binding. Mol. Cell, 2003, 11(5), 1389-1396.
99. Comerford, K.M.; Leonard, M.O.; Karhausen, J.; Carey, R.; Colgan, S.P.; Taylor, C.T. Small ubiquitin-related modifier-1 modification mediates resolution of CREB-dependent responses to hypoxia. Proc. Natl. Acad. Sci. USA, 2003, 100(3), 986-991.
100. Du, J.X.; Bialkowska, A.B.; McConnell, B.B.; Yang, V.W. SUMOylation regulates nuclear localization of Kruppel-like factor 5. J. Biol. Chem., 2008, 283(46), 31991-32002.
101. Ohshima, T.; Shimotohno, K. Transforming growth factor-betamediated signaling via the p38 MAP kinase pathway activates Smad-dependent transcription through SUMO-1 modification of Smad4. J. Biol. Chem., 2003, 278(51), 50833-50842.
102. Johnson, E.S. Protein modification by SUMO. Annu. Rev. Biochem., 2004, 73, 355-382.
103. Schwartz, D.C.; Hochstrasser, M. A superfamily of protein tags: ubiquitin, SUMO and related modifiers. Trends Biochem. Sci., 2003, 28(6), 321-328.
104. Muller, S.; Ledl, A.; Schmidt, D. SUMO: a regulator of gene expression and genome integrity. Oncogene, 2004, 23(11), 1998-2008.
105. Liu, G.H.; Gerace, L. Sumoylation regulates nuclear localization of lipin-1alpha in neuronal cells. PLoS One, 2009, 4(9), e7031.
106. Corcoran, A.; Cotter, T.G. Redox regulation of protein kinases. FEBS J., 280(9), 1944-1965.
107. Bartosz, G. Reactive oxygen species: destroyers or messengers? Biochem. Pharmacol., 2009, 77(8), 1303-1315.
108. Davies, M.J. The oxidative environment and protein damage. Biochim. Biophys. Acta, 2005, 1703(2), 93-109.
109. Grimsrud, P.A.; Xie, H.; Griffin, T.J.; Bernlohr, D.A. Oxidative stress and covalent modification of protein with bioactive aldehydes. J. Biol. Chem., 2008, 283(32), 21837-21841.
110. Dalle-Donne, I.; Rossi, R.; Giustarini, D.; Milzani, A.; Colombo, R. Protein carbonyl groups as biomarkers of oxidative stress. Clin. Chim. Acta, 2003, 329(1-2), 23-38.
111. Hoshi, T.; Heinemann, S. Regulation of cell function by methionine oxidation and reduction. J. Physiol., 2001, 531(Pt. 1), 1-11.
112. Janssen-Heininger, Y.M.; Mossman, B.T.; Heintz, N.H.; Forman, H.J.; Kalyanaraman, B.; Finkel, T.; Stamler, J.S.; Rhee, S.G.; van der Vliet, A. Redox-based regulation of signal transduction: principles, pitfalls, and promises. Free Radic. Biol. Med., 2008, 45(1), 1-17.
113. Ahn, S.G.; Thiele, D.J. Redox regulation of mammalian heat shock factor 1 is essential for Hsp gene activation and protection from stress. Genes Dev., 2003, 17(4), 516-528.
114. Sumbayev, V.V.; Yasinska, I.M. Regulation of MAP kinasedependent apoptotic pathway: implication of reactive oxygen and nitrogen species. Arch. Biochem. Biophys., 2005, 436(2), 406-412.
115. Liu, B.; Chen, Y.; St Clair, D.K. ROS and p53: a versatile partnership. Free Radic. Biol. Med., 2008, 44(8), 1529-1535.
116. Gronemeyer, H.; Gustafsson, J.A.; Laudet, V. Principles for modulation of the nuclear receptor superfamily. Nat. Rev. Drug Discov., 2004, 3(11), 950-964.
117. Karamouzis, M.V.; Gorgoulis, V.G.; Papavassiliou, A.G. Transcription factors and neoplasia: vistas in novel drug design. Clin. Cancer Res., 2002, 8(5), 949-961.
118. Emery, J.G.; Ohlstein, E.H.; Jaye, M. Therapeutic modulation of transcription factor activity. Trends Pharmacol. Sci., 2001, 22(5), 233-240.
119. Gane, P.J.; Dean, P.M. Recent advances in structure-based rational drug design. Curr. Opin. Struct. Biol., 2000, 10(4), 401-404.
120. Latchman, D.S. Transcription-factor mutations and disease. N. Engl. J. Med., 1996, 334(1), 28-33.
121. Latchman, D.S. How can we use our growing understanding of gene transcription to discover effective new medicines? Curr. Opin. Biotechnol., 1997, 8(6), 713-717.
122. Papavassiliou, A.G. Molecular medicine. Transcription factors. N. Engl. J. Med., 1995, 332(1), 45-47.
123. Papavassiliou, A.G. Transcription-factor-modulating agents: precision and selectivity in drug design. Mol. Med. Today, 1998, 4(8), 358-366.
124. Arnott, J. A.; Planey, S. L., The influence of lipophilicity in drug discovery and design. Expert. Opin. Drug Discov., 2012, 7(10), 863-875.
125. Brzozowski, A.M.; Pike, A.C.; Dauter, Z.; Hubbard, R.E.; Bonn, T.; Engstrom, O.; Ohman, L.; Greene, G.L.; Gustafsson, J.A.; Carlquist, M. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature, 1997, 389(6652), 753-758.
126. Lee, B.I.; Park, S.H.; Kim, J.W.; Sausville, E.A.; Kim, H.T.; Nakanishi, O.; Trepel, J.B.; Kim, S.J. MS-275, a histone deacetylase inhibitor, selectively induces transforming growth factor beta type II receptor expression in human breast cancer cells. Cancer Res., 2001, 61(3), 931-934.
127. Huang, L.; Sowa, Y.; Sakai, T.; Pardee, A.B. Activation of the p21WAF1/CIP1 promoter independent of p53 by the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) through the Sp1 sites. Oncogene, 2000, 19(50), 5712-5719.
128. MacLaine, N.J.; Hupp, T.R. How phosphorylation controls p53. Cell Cycle, 2011, 10(6), 916-921.
129. Devine, T.; Dai, M.S. Targeting the ubiquitin-mediated proteasome degradation of p53 for cancer therapy. Curr. Pharm. Des., 2012, 19(18), 3248-3262.
130. Lavin, M.F.; Gueven, N. The complexity of p53 stabilization and activation. Cell Death Differ, 2006, 13(6), 941-950.