Characterizations of three major cysteine sensors of Keap1 in stress response

Molecular and Cellular Biology

Volumn 36, Issue 2, 2016, Pages 271-284

  Saito, Ryota ^a   Suzuki, Takafumi ^a   Hiramoto, Keiichiro ^a   Asami, Soichiro ^a   Naganuma, Eriko ^a   Suda, Hiromi ^a   Iso, Tatsuro ^a   Yamamoto, Hirotaka ^a   Morita, Masanobu ^a   Baird, Liam ^a   Furusawa, Yuki ^b   Negishi, Takaaki ^b   Ichinose, Masakazu ^a   Yamamoto, Masayuki ^a  

^a TOHOKU UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

^b MOCHIDA PHARMACEUTICAL CO   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE; ASPARAGINE; CYSTEINE; GLUTAMIC ACID; KELCH LIKE ECH ASSOCIATED PROTEIN 1; SERINE; TRANSCRIPTION FACTOR NRF2; CYTOSKELETON PROTEIN; KEAP1 PROTEIN, HUMAN; KEAP1 PROTEIN, MOUSE; NFE2L2 PROTEIN, HUMAN; NFE2L2 PROTEIN, MOUSE; SIGNAL PEPTIDE; SIGNAL TRANSDUCING ADAPTOR PROTEIN;

AMINO ACID SUBSTITUTION; AMINO TERMINAL SEQUENCE; ANIMAL EXPERIMENT; ARTICLE; CELL PROTECTION; COMPARATIVE STUDY; CONTROLLED STUDY; ENVIRONMENTAL STRESS; FIBROBLAST; GENE SEQUENCE; HUMAN; HUMAN CELL; MOLECULAR SENSOR; MURINE EMBRYONIC FIBROBLAST; NONHUMAN; PERITONEUM MACROPHAGE; POINT MUTATION; PRIORITY JOURNAL; PROTEIN FUNCTION; QUANTITATIVE ANALYSIS; REAL TIME POLYMERASE CHAIN REACTION; TRANSGENIC MOUSE; AMINO ACID SEQUENCE; ANIMAL; CELL LINE; CHEMISTRY; GENETIC TRANSFECTION; GENETICS; HEK293 CELL LINE; METABOLISM; MOLECULAR GENETICS; MOUSE; MUTATION; OXIDATIVE STRESS; SEQUENCE ALIGNMENT;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; ANIMALS; CELL LINE; CYSTEINE; CYTOSKELETAL PROTEINS; HEK293 CELLS; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; KELCH-LIKE ECH-ASSOCIATED PROTEIN 1; MICE; MICE, TRANSGENIC; MOLECULAR SEQUENCE DATA; MUTATION; NF-E2-RELATED FACTOR 2; OXIDATIVE STRESS; SEQUENCE ALIGNMENT; TRANSFECTION;

EID: 84954180344     PISSN: 02707306     EISSN: 10985549     Source Type: Journal    
DOI: 10.1128/MCB.00868-15     Document Type: Article

References (46)

1. Itoh K, Chiba T, Takahashi S, Ishii T, Igarashi K, Katoh Y, Oyake T, Hayashi N, Satoh K, Hatayama I, Yamamoto M, Nabeshima Y. 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. http://dx.doi.org/10.1006/bbrc.1997.6943.
2. Itoh K, Wakabayashi N, Katoh Y, Ishii T, Igarashi K, Engel JD, 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. http://dx.doi.org/10.1101/gad.13.1.76.
3. Kobayashi A, Kang MI, Okawa H, Ohtsuji M, Zenke Y, Chiba T, Igarashi K, 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. http://dx.doi.org/10.1128/MCB.24.16.7130-7139.2004.
4. Suzuki T, Shibata T, Takaya K, Shiraishi K, Kohno T, Kunitoh H, Tsuta K, Furuta K, Goto K, Hosoda F, Sakamoto H, Motohashi H, Yamamoto M. 2013. Regulatory nexus of synthesis and degradation deciphers cellular Nrf2 expression levels. Mol Cell Biol 33:2402-2412. http://dx.doi.org/10.1128/MCB.00065-13.
5. Taguchi K, Hirano I, Itoh T, Tanaka M, Miyajima A, Suzuki A, Motohashi H, Yamamoto M. 2014. Nrf2 enhances cholangiocyte expansion in Pten-deficient livers. Mol Cell Biol 34:900-913. http://dx.doi.org/10.1128/MCB.01384-13.
6. Uruno A, Furusawa Y, Yagishita Y, Fukutomi T, Muramatsu H, Negishi T, Sugawara A, Kensler TW, Yamamoto M. 2013. The Keap1-Nrf2 system prevents onset of diabetes mellitus. Mol Cell Biol 33:2996-3010. http://dx.doi.org/10.1128/MCB.00225-13.
7. Suzuki T, Yamamoto M. Molecular basis of the Keap1-Nrf2 system. Free Radic Biol Med 88:93-100. http://dx.doi.org/10.1016/j.freeradbiomed.2015.06.006.
8. Suzuki T, Motohashi H, Yamamoto M. 2013. Toward clinical application of the Keap1-Nrf2 pathway. Trends Pharmacol Sci 34:340-346. http://dx.doi.org/10.1016/j.tips.2013.04.005.
9. Dinkova-Kostova AT, Talalay P. 2008. Direct and indirect antioxidant properties of inducers of cytoprotective proteins. Mol Nutr Food Res 52(Suppl 1):S128-S138. http://dx.doi.org/10.1002/mnfr.200700195.
10. Dinkova-Kostova AT, Holtzclaw WD, Cole RN, Itoh K, Wakabayashi N, Katoh Y, Yamamoto M, Talalay P. 2002. Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants. Proc Natl Acad Sci U S A 99:11908-11913. http://dx.doi.org/10.1073/pnas.172398899.
11. Hong F, Freeman ML, Liebler DC. 2005. Identification of sensor cysteines in human Keap1 modified by the cancer chemopreventive agent sulforaphane. Chem Res Toxicol 18:1917-1926. http://dx.doi.org/10.1021/tx0502138.
12. Eggler AL, Liu G, Pezzuto JM, van Breemen RB, Mesecar AD. 2005. Modifying specific cysteines of the electrophile-sensing human Keap1 protein is insufficient to disrupt binding to the Nrf2 domain Neh2. Proc Natl Acad Sci U S A 102:10070-10075. http://dx.doi.org/10.1073/pnas.0502402102.
13. Eggler AL, Luo Y, van Breemen RB, Mesecar AD. 2007. Identification of the highly reactive cysteine 151 in the chemopreventive agent-sensor Keap1 protein is method dependent. Chem Res Toxicol 20:1878-1884. http://dx.doi.org/10.1021/tx700217c.
14. Kobayashi M, Li L, Iwamoto N, Nakajima-Takagi Y, Kaneko H, Nakayama Y, Eguchi M, Wada Y, Kumagai Y, Yamamoto M. 2009. The antioxidant defense system Keap1-Nrf2 comprises a multiple sensing mechanism for responding to a wide range of chemical compounds. Mol Cell Biol 29:493-502. http://dx.doi.org/10.1128/MCB.01080-08.
15. Tsujita T, Li L, Nakajima H, Iwamoto N, Nakajima-Takagi Y, Ohashi K, Kawakami K, Kumagai Y, Freeman BA, Yamamoto M, Kobayashi M. 2011. Nitro-fatty acids and cyclopentenone prostaglandins share strategies to activate the Keap1-Nrf2 system: a study using green fluorescent protein transgenic zebrafish. Genes Cells 16:46-57. http://dx.doi.org/10.1111/j.1365-2443.2010.01466.x.
16. Kansanen E, Bonacci G, Schopfer FJ, Kuosmanen SM, Tong KI, Leinonen H, Woodcock SR, Yamamoto M, Carlberg C, Ylä-Herttuala S, Freeman BA, Levonen AL. 2011. Electrophilic nitro-fatty acids activate NRF2 by a KEAP1 cysteine 151-independent mechanism. J Biol Chem 286:14019-14027. http://dx.doi.org/10.1074/jbc.M110.190710.
17. Hu C, Eggler AL, Mesecar AD, van Breemen RB. 2011. Modification of keap1 cysteine residues by sulforaphane. Chem Res Toxicol 24:515-521. http://dx.doi.org/10.1021/tx100389r.
18. Zhang DD, Hannink M. 2003. Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress. Mol Cell Biol 23:8137-8151. http://dx.doi.org/10.1128/MCB.23.22.8137-8151.2003.
19. Wakabayashi N, Dinkova-Kostova AT, Holtzclaw WD, Kang MI, Kobayashi A, Yamamoto M, Kensler TW, Talalay P. 2004. Protection against electrophile and oxidant stress by induction of the phase 2 response: fate of cysteines of the Keap1 sensor modified by inducers. Proc Natl Acad Sci U S A 101:2040-2045. http://dx.doi.org/10.1073/pnas.0307301101.
20. Eggler AL, Small E, Hannink M, Mesecar AD. 2009. Cul3-mediated Nrf2 ubiquitination and antioxidant response element (ARE) activation are dependent on the partial molar volume at position 151 of Keap1. Biochem J 422:171-180. http://dx.doi.org/10.1042/BJ20090471.
21. Yamamoto T, Suzuki T, Kobayashi A, Wakabayashi J, Maher J, Motohashi H, Yamamoto M. 2008. Physiological significance of reactive cysteine residues of Keap1 in determining Nrf2 activity. Mol Cell Biol 28: 2758-2770. http://dx.doi.org/10.1128/MCB.01704-07.
22. Takaya K, Suzuki T, Motohashi H, Onodera K, Satomi S, Kensler TW, Yamamoto M. 2012. Validation of the multiple sensor mechanism of the Keap1-Nrf2 system. Free Radic Biol Med 53:817-827. http://dx.doi.org/10.1016/j.freeradbiomed.2012.06.023.
23. Hirotsu Y, Katsuoka F, Itoh K, Yamamoto M. 2011. Nrf2 degron-fused reporter system: a new tool for specific evaluation of Nrf2 inducers. Genes Cells 16:406-415. http://dx.doi.org/10.1111/j.1365-2443.2011.01496.x.
24. Kang MI, Kobayashi A, Wakabayashi N, Kim SG, Yamamoto M. 2004. Scaffolding of Keap1 to the actin cytoskeleton controls the function of Nrf2 as key regulator of cytoprotective phase 2 genes. Proc Natl Acad Sci U S A 101:2046-2051. http://dx.doi.org/10.1073/pnas.0308347100.
25. Wakabayashi N, Itoh K, Wakabayashi J, Motohashi H, Noda S, Takahashi S, Imakado S, Kotsuji T, Otsuka F, Roop DR, Harada T, Engel JD, Yamamoto M. 2003. Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation. Nat Genet 35:238-245. http://dx.doi.org/10.1038/ng1248.
26. Ohta T, Iijima K, Miyamoto M, Nakahara I, Tanaka H, Ohtsuji M, Suzuki T, Kobayashi A, Yokota J, Sakiyama T, Shibata T, Yamamoto M, Hirohashi S. 2008. Loss of Keap1 function activates Nrf2 and provides advantages for lung cancer cell growth. Cancer Res 68:1303-1309. http://dx.doi.org/10.1158/0008-5472.CAN-07-5003.
27. Suzuki T, Kelly VP, Motohashi H, Nakajima O, Takahashi S, Nishimura S, Yamamoto M. 2008. Deletion of the selenocysteine tRNA gene in macrophages and liver results in compensatory gene induction of cytoprotective enzymes by Nrf2. J Biol Chem 283:2021-2030. http://dx.doi.org/10.1074/jbc.M708352200.
28. Maruyama A, Tsukamoto S, Nishikawa K, Yoshida A, Harada N, Motojima K, Ishii T, Nakane A, Yamamoto M, Itoh K. 2008. Nrf2 regulates the alternative first exons of CD36 in macrophages through specific antioxidant response elements. Arch Biochem Biophys 477:139-145. http://dx.doi.org/10.1016/j.abb.2008.06.004.
29. Watai Y, Kobayashi A, Nagase H, Mizukami M, McEvoy J, Singer JD, Itoh K, Yamamoto M. 2007. Subcellular localization and cytoplasmic complex status of endogenous Keap1. Genes Cells 12:1163-1178. http://dx.doi.org/10.1111/j.1365-2443.2007.01118.x.
30. Wang H, Yang H, Shivalila CS, Dawlaty MM, Cheng AW, Zhang F, Jaenisch R. 2013. One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering. Cell 153: 910-918. http://dx.doi.org/10.1016/j.cell.2013.04.025.
31. Suzuki T, Maher J, Yamamoto M. 2011. Select heterozygous Keap1 mutations have a dominant-negative effect on wild-type Keap1 in vivo. Cancer Res 71:1700-1709. http://dx.doi.org/10.1158/1538-7445.AM2011-1700.
32. Dhanoa BS, Cogliati T, Satish AG, Bruford EA, Friedman JS. 2013. Update on the Kelch-like (KLHL) gene family. Hum Genomics 7:13. http://dx.doi.org/10.1186/1479-7364-7-13.
33. Canning P, Cooper CD, Krojer T, Murray JW, Pike AC, Chaikuad A, Keates T, Thangaratnarajah C, Hojzan V, Ayinampudi V, Marsden BD, Gileadi O, Knapp S, von Delft F, Bullock AN. 2013. Structural basis for Cul3 protein assembly with the BTB-Kelch family of E3 ubiquitin ligases. J Biol Chem 288:7803-7814. http://dx.doi.org/10.1074/jbc.M112.437996.
34. McMahon M, Lamont DJ, Beattie KA, Hayes JD. 2010. Keap1 perceives stress via three sensors for the endogenous signaling molecules nitric oxide, zinc, and alkenals. Proc Natl Acad Sci U S A 107:18838-18843. http://dx.doi.org/10.1073/pnas.1007387107.
35. Hourihan JM, Kenna JG, Hayes JD. 2013. The gasotransmitter hydrogen sulfide induces nrf2-target genes by inactivating the keap1 ubiquitin ligase substrate adaptor through formation of a disulfide bond between cys-226 and cys-613. Antioxid Redox Signal 19:465-481. http://dx.doi.org/10.1089/ars.2012.4944.
36. Fujii S, Sawa T, Ihara H, Tong KI, Ida T, Okamoto T, Ahtesham AK, Ishima Y, Motohashi H, Yamamoto M, Akaike T. 2010. The critical role of nitric oxide signaling, via protein S-guanylation and nitrated cyclic GMP, in the antioxidant adaptive response. J Biol Chem 285:23970-23984. http://dx.doi.org/10.1074/jbc.M110.145441.
37. Ogura T, Tong KI, Mio K, Maruyama Y, Kurokawa H, Sato C, 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. http://dx.doi.org/10.1073/pnas.0914036107.
38. Tong KI, Padmanabhan B, Kobayashi A, Shang C, Hirotsu Y, Yokoyama S, Yamamoto M. 2007. Different electrostatic potentials define ETGE and DLG motifs as hinge and latch in oxidative stress response. Mol Cell Biol 27:7511-7521. http://dx.doi.org/10.1128/MCB.00753-07.
39. Fukutomi T, Takagi K, Mizushima T, Ohuchi N, Yamamoto M. 2014. Kinetic, thermodynamic, and structural characterizations of the association between Nrf2-DLGex degron and Keap1. Mol Cell Biol 34:832-846. http://dx.doi.org/10.1128/MCB.01191-13.
40. Shibata T, Ohta T, Tong KI, Kokubu A, Odogawa R, Tsuta K, Asamura H, Yamamoto M, Hirohashi S. 2008. Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy. Proc Natl Acad Sci U S A 105:13568-13573. http://dx.doi.org/10.1073/pnas.0806268105.
41. Zhang DD, Lo SC, Cross JV, Templeton DJ, Hannink M. 2004. Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex. Mol Cell Biol 24:10941-10953. http://dx.doi.org/10.1128/MCB.24.24.10941-10953.2004.
42. Gao L, Wang J, Sekhar KR, Yin H, Yared NF, Schneider SN, Sasi S, Dalton TP, Anderson ME, Chan JY, Morrow JD, Freeman ML. 2007. Novel n-3 fatty acid oxidation products activate Nrf2 by destabilizing the association between Keap1 and Cullin3. J Biol Chem 282:2529-2537. http://dx.doi.org/10.1074/jbc.M607622200.
43. Rachakonda G, Xiong Y, Sekhar KR, Stamer SL, Liebler DC, Freeman ML. 2008. Covalent modification at Cys151 dissociates the electrophile sensor Keap1 from the ubiquitin ligase CUL3. Chem Res Toxicol 21:705-710. http://dx.doi.org/10.1021/tx700302s.
44. Cleasby A, Yon J, Day PJ, Richardson C, Tickle IJ, Williams PA, Callahan JF, Carr R, Concha N, Kerns JK, Qi H, Sweitzer T, Ward P, Davies TG. 2014. Structure of the BTB domain of Keap1 and its interaction with the triterpenoid antagonist CDDO. PLoS One 9:e98896. http://dx.doi.org/10.1371/journal.pone.0098896.
45. Li Y, Paonessa JD, Zhang Y. 2012. Mechanism of chemical activation of Nrf2. PLoS One 7:e35122. http://dx.doi.org/10.1371/journal.pone.0035122.
46. Baird L, Dinkova-Kostova AT. 2013. Diffusion dynamics of the Keap1-Cullin3 interaction in single live cells. Biochem Biophys Res Commun 433:58-65. http://dx.doi.org/10.1016/j.bbrc.2013.02.065.