Identification of sensor cysteines in human Keap1 modified by the cancer chemopreventive agent sulforaphane

Chemical Research in Toxicology

Volumn 18, Issue 12, 2005, Pages 1917-1926

  Hong, Fei ^a   Freeman, Michael L ^b   Liebler, Daniel C ^b  

^a UNIVERSITY OF ARIZONA   (United States)

^b VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; ANTIOXIDANT; CYSTEINE; ISOTHIOCYANIC ACID DERIVATIVE; KEAP1 PROTEIN; PROTEIN; SULFORAPHANE; THIOL GROUP; TRANSCRIPTION FACTOR NRF2; UBIQUITIN; UNCLASSIFIED DRUG;

ACYLATION; ALKYLATION; AMINO ACID ANALYSIS; ARTICLE; CANCER PREVENTION; CONTROLLED STUDY; DNA RESPONSIVE ELEMENT; ELECTRON; ELECTROPHILE; ELECTROPHILE RESPONSE ELEMENT; GENE INDUCTION; HUMAN; HUMAN CELL; HYDROLYSIS; KELCH DOMAIN; LIQUID CHROMATOGRAPHY; MOLECULAR INTERACTION; MOLECULAR STABILITY; PROTEIN DOMAIN; PROTEIN MODIFICATION; TANDEM MASS SPECTROMETRY; THIONOACYL ADDUCT; TRANSACTIVATION; TRANSACYLATION;

AMINO ACID SEQUENCE; ANTINEOPLASTIC AGENTS; CELLS, CULTURED; CYSTEINE; DNA ADDUCTS; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; MASS SPECTROMETRY; MOLECULAR SEQUENCE DATA; NF-E2-RELATED FACTOR 2; PROTEINS; THIOCYANATES;

EID: 29644443964     PISSN: 0893228X     EISSN: None     Source Type: Journal    
DOI: 10.1021/tx0502138     Document Type: Article

References (56)

1. Block, G., Patterson, B., and Subar, A. (1992) Fruit, vegetables, and cancer prevention: A review of the epidemiological evidence. Nutr. Cancer 18, 1-29.
2. Michaud, D. S., Spiegelman, D., Clinton, S. K., Rimm, E. B., Curhan, G. C., Willett, W. C., and Giovannucci, E. L. (1999) Fluid intake and the risk of bladder cancer in men. N. Engl. J. Med. 340, 1390-1397.
3. Michaud, D. S., Spiegelman, D., Clinton, S. K., Rimm, E. B., Willett, W. C., and Giovannucci, E. L. (1999) Fruit and vegetable intake and incidence of bladder cancer in a male prospective cohort. J. Natl. Cancer Inst. 91, 605-613.
4. Verhoeven, D. T., Goldbohm, R. A., van, P. G., Verhagen, H., and Van den Brandt, P. A. (1996) Epidemiological studies on brassica vegetables and cancer risk. Cancer Epidemiol. Blomarkers Prev. 5, 733-748.
5. Fahey, J. W., Zhang, Y., and Talalay, P. (1997) Broccoli sprouts: An exceptionally rich source of inducers of enzymes that protect against chemical carcinogens. Proc. Natl. Acad. Sci. U.S.A. 94, 10367-10372.
6. Prochaska, H. J., Santamaria, A. B., and Talalay, P. (1992) Rapid detection of inducers of enzymes that protect against carcinogens. Proc. Natl. Acad. Sci. U.S.A. 89, 2394-2398.
7. Zhang, Y., Talalay, P., Cho, C. G., and Posner, G. H. (1992) A major inducer of anticarcinogenic protective enzymes from broccoli: Isolation and elucidation of structure. Proc. Natl. Acad. Sci. U.S.A. 89, 2399-2403.
8. Gerhauser, C., You, M., Liu, J., Moriarty, R. M., Hawthorne, M., Mehta, R. G., Moon, R. C., and Pezzuto, J. M. (1997) Cancer chemopreventive potential of sulforamate, a novel analogue of sulforaphane that induces phase 2 drug-metabolizing enzymes. Cancer Res. 57, 272-278.
9. Chung, F. L., Conaway, C. C., Rao, C. V., and Reddy, B. S. (2000) Chemoprevention of colonic aberrant crypt foci in Fischer rats by sulforaphane and phenethyl isothiocyanate. Carcinogenesis 21, 2287-2291.
10. Chiao, J. W., Chung, F. L., Kancherla, R., Ahmed, T., Mittelman, A., and Conaway, C. C. (2002) Sulforaphane and its metabolite mediate growth arrest and apoptosis in human prostate cancer cells. Int. J. Oncol. 20, 631-636.
11. Talalay, P., Fahey, J. W., Holtzclaw, W. D., Prestera, T., and Zhang, Y. (1995) Chemoprotection against cancer by phase 2 enzyme induction. Toxicol. Lett. 82-83, 173-179.
12. Rushmore, T. H., Morton, M. R., and Pickett, C. B. (1991) The antioxidant response element. Activation by oxidative stress and identification of the DNA concensus sequence required for functional activity. J. Biol. Chem. 266, 11632-11639.
13. Favreau, L. V., and Pickett, C. B. (1991) Transcriptional regulation of the rat NAD(P)H:quinone reductase gene. Identification of regulatory elements controlling basal level expression and inducible expression by planar aromatic compounds and phenolic antioxidants. J. Biol. Chem. 266, 4556-4561.
14. Moi, P., Chan, K., Asunis, L, 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 beta-globin locus control region. Proc. Natl. Acad. Sci. U.S.A. 91, 9926-9930.
15. Itoh, K., Chiba, T., Takahashi, S., Ishii, T., Igarashi, K., Katoh, Y., Oyake, T., Hayashi, N., Satoh, K., Hatayama, I., Yamamoto, M., and 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.
16. 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.
17. Keum, Y. S., Owuor, E. D., Kim, B. R., Hu, R., and Kong, A. N. (2003) Involvement of Nrf2 and JNK1 in the activation of antioxidant responsive element (ARE) by chemopreventive agent phenethyl isothiocyanate (PEITC). Pharm. Res. 20, 1351-1356.
18. Chan, K., and Kan, Y. W. (1999) Nrf2 is essential for protection against acute pulmonary injury in mice. Proc. Natl. Acad. Sci. U.S.A. 96, 12731-12736.
19. Chan, K., Han, X. D., and Kan, Y. W. (2001) An important function of Nrf2 in combating oxidative stress: Detoxification of acetaminophen. Proc. Natl. Acad. Sci. U.S.A. 98, 4611-4616.
20. Enomoto, A., Itoh, K., Nagayoshi, E., Haruta, J., Kimura, T., O'Connor, T., Harada, T., and Yamamoto, M. (2001) High sensitivity of Nrf2 knockout mice to acetaminophen hepatotoxicity associated with decreased expression of ARE-regulated drug metabolizing enzymes and antioxidant genes. Toxicol. Sci. 59, 169-177.
21. 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.
22. Hayes, J. D., and McMahon, M. (2001) Molecular basis for the contribution of the antioxidant responsive element to cancer chemoprevention. Cancer Lett. 174, 103-113.
23. Thimmulappa, R. K., Mai, K. H., Srisuma, S., Kensler, T. W., Yamamoto, M., and Biswal, S. (2002) Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray. Cancer Res. 62, 5196-5203.
24. 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.
25. Dhakshinamoorthy, S., and Jaiswal, A. K. (2001) Functional characterization and role of INrf2 in antioxidant response element-mediated expression and antioxidant induction of NAD(P)H: quinone oxidoreductase1 gene. Oncogene 20, 3906-3917.
26. Itoh, K., Wakabayashi, N., Katoh, Y., Ishii, T., O'Connor, T., and Yamamoto, M. (2003) Keap1 regulates both cytoplasmic-nuclear shuttling and degradation of Nrf2 in response to electrophiles. Genes Cells 8, 379-391.
27. Zipper, L. M., and Mulcahy, R. T. (2002) The Keap1 BTB/POZ dimerization function is required to sequester Nrf2 in cytoplasm. J. Biol. Chem. 277, 36544-36552.
28. Zhang, D. D., and 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.
29. Kang, M. I., Kobayashi, A., Wakabayashi, N., Kim, S. G., and 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.
30. Velichkova, M., and Hasson, T. (2005) Keap1 regulates the oxidation-sensitive shuttling of Nrf2 in to and out of the nucleus via a Crm1-dependent nuclear export mechanism. Mol. Cell Biol. 25, 4501-4513.
31. 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.
32. Zhang, D. D., Lo, S. C., Cross, J. V., Templeton, D. J., and Hannink, M. (2004) Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex. Mol. Cell Biol. 24, 10941-10953.
33. Cullinan, S. B., Gordan, J. D., Jin, J., Harper, J. W., and Diehl, J. A. (2004) The Keap1-BTB protein is an adaptor that bridges Nrf2 to a Cul3-based E3 ligase: Oxidative stress sensing by a Cul3-Keap1 ligase. Mol. Cell Biol. 24, 8477-8486.
34. Furukawa, M., and Xiong, Y. (2005) BTB protein Keap1 targets antioxidant transcription factor Nrf2 for ubiquitination by the Cullin 3-Roc1 ligase. Mol. Cell Biol. 25, 162-171.
35. Nguyen, T., Sherratt, P. J., Nioi, P., Yang, C. S., and Pickett, C. B. (2005) NRF2 controls constitutive and inducible expression of are-driven genes through a dynamic pathway involving nucleo-cytoplasmic shuttling by keap1. J. Biol. Chem. 280, 32485-32492.
36. Wakabayashi, N., Dinkova-Kostova, A. T., Holtzclaw, W. D., Kang, M. I., Kobayashi, A., Yamamoto, M., Kensler, T. W., and 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.
37. Hong, F., Sekhar, K. R., Freeman, M. L., and Liebler, D. C. (2005) Specific patterns of electrophile adduction trigger Keap1 ubiquitination and Nrf2 activation. J. Biol. Chem. 280, 31768-31775.
38. Eggler, A. L., Liu, G., Pezzuto, J. M., van Breemen, R. B., and Mesecar, A. D. (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.
39. Zhang, D. D., Lo, S. C., Sun, Z., Habib, G. M., Lieberman, M. W., and Hannink, M. (2005) Ubiquitination of Keap1, a BTB-Kelch substrate adaptor protein for Cul3, targets Keap1 for degradation by a proteosome-independent pathway. J. Biol. Chem. 280, 30091-30099.
40. McWalter, G. K., Higgins, L. G., McLellan, L. I., Henderson, C. J., Song, L., Thornalley, P. J., Itoh, K., Yamamoto, M., and Hayes, J. D. (2004) Transcription factor Nrf2 is essential for induction of NAD(P)H:quinone oxidoreductase 1, glutathione S-transferases, and glutamate cysteine ligase by broccoli seeds and isothiocyanates. J. Nutr. 134, 3499S-3506S.
41. Gao, X., and Talalay, P. (2004) Induction of phase 2 genes by sulforaphane protects retinal pigment epithelial cells against photooxidative damage. Proc. Natl. Acad. Sci. U.S.A. 101, 10446-10451.
42. Kraft, A. D., Johnson, D. A., and Johnson, J. A. (2004) Nuclear factor E2-related factor 2-dependent antioxidant response element activation by tert-butylhydroquinone and sulforaphane occurring preferentially in astrocytes conditions neurons against oxidative insult. J. Neurosci. 24, 1101-1112.
43. Jones, J. A., and Liebler, D. C. (2000) Tandem MS analysis of model peptide adducts from reactive metabolites of the hepatotoxin 1,1-dichloroethylene. Chem. Res. Toxicol. 13, 1302-1312.
44. Mason, D. E., and Liebler, D. C. (2000) Characterization of benzoquinone-peptide adducts by electrospray mass spectrometry. Chem. Res. Toxicol. 13, 976-982.
45. Hecht, S. S. (2000) Inhibition of carcinogenesis by isothiocyanates. Drug Metab. Rev. 32, 395-411.
46. Dinkova-Kostova, A. T., Holtzclaw, W. D., Cole, R. N., Itoh, K., Wakabayashi, N., Katoh, Y., Yamamoto, M., and 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.
47. Dinkova-Kostova, A. T., Holtzclaw, W. D., and Wakabayashi, N. (2005) Keap1, the sensor for electrophiles and oxidants that regulates the phase 2 response, is a zinc metalloprotein. Biochemistry 44, 6889-6899.
48. Liebler, D. C., Latwesen, D. G., and Reeder, T. C. (1988) S-(2-Chloroacetyl)glutathione, a reactive glutathione thiolester and a putative metabolite of 1,1-dichloroethylene. Biochemistry 27, 3652-3657.
49. Jones, J. A., Kaphalia, L., Treinen-Moslen, M., and Liebler, D. C. (2003) Proteomic characterization of metabolites, protein adducts, and biliary proteins in rats exposed to 1,1-dichloroethylene or diclofenac. Chem. Res. Toxicol. 16, 1306-1317.
50. Stahl, D. C., Swiderek, K. M., Davis, M. T., and Lee, T. D. (1995) Data-controlled automation of liquid chromatography/tandem mass spectrometry analysis of peptide mixtures. J. Am. Soc. Mass Spectrom. 7, 532-540.
51. Washburn, M. P., Wolters, D., and Yates, J. R. (2001) Large-scale analysis of the yeast proteome by multidimensional protein identification technology. Nat. Biotechnol. 19, 242-247.
52. Peng, J., Elias, J. E., Thoreen, C. C., Licklider, L. J., and Gygi, S. P. (2003) Evaluation of multidimensional chromatography coupled with tandem mass spectrometry (LC/LC-MS/MS) for large scale protein analysis: the yeast proteome. J. Proteome Res. 2, 43-50.
53. Gao, J., Opiteck, G. J., Friedrichs, M. S., Dongre, A. R., and Hefta, S. A. (2003) Changes in the protein expression of yeast as a function of carbon source. J. Proteome. Res. 2, 643-649.
54. Julka, S., and Regnier, F. (2004) Quantification in proteomics through stable isotope coding: A review. J. Proteome. Res. 3, 350-363.
55. Gerber, S. A., Rush, J., Stemman, O., Kirschner, M. W., and Gygi, S. P. (2003) Absolute quantification of proteins and phosphoproteins from cell lysates by tandem MS. Proc. Natl. Acad. Sci. U.S.A. 100, 6940-6945.
56. 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.