Identification of the highly reactive cysteine 151 in the chemopreventive agent-sensor Keap1 protein is method-dependent

Chemical Research in Toxicology

Volumn 20, Issue 12, 2007, Pages 1878-1884

  Eggler, Aimee L ^a   Luo, Yan ^a   Van Breemen, Richard B ^a   Mesecar, Andrew D ^a  

^a UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYSTEINE 151; CYSTEINE DERIVATIVE; IODOACETAMIDE; KELCH LIKE ECH ASSOCIATED PROTEIN 1; REDUCING AGENT; UNCLASSIFIED DRUG;

ARTICLE; MOLECULAR SENSOR; PROTEIN ANALYSIS; PROTEIN MODIFICATION; ULTRACENTRIFUGATION;

ANTIOXIDANTS; BIOTINYLATION; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CYSTEINE; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; IODOACETAMIDE; NF-E2-RELATED FACTOR 2; PEPTIDES; PROTECTIVE AGENTS; PROTEOMICS; RESPONSE ELEMENTS; TANDEM MASS SPECTROMETRY;

EID: 36349019109     PISSN: 0893228X     EISSN: None     Source Type: Journal    
DOI: 10.1021/tx700217c     Document Type: Article

References (21)

1. Kobayashi, M., and Yamamoto, M. (2005) Molecular mechanisms activating the Nrf2-Keap1 pathway of antioxidant gene regulation. Antioxid. Redox Signaling 7, 385-394.
2. Talalay, P., Dinkova-Kostova, A. T., and Holtzclaw, W. D. (2003) Importance of phase 2 gene regulation in protection against electrophile and reactive oxygen toxicity and carcinogenesis. Adv. Enzyme Regul. 43, 121-134.
3. Ramos-Gomez, M., Kwak, M. K., Dolan, P. M., Itoh, K., Yamamoto, M., Talalay, P., and Kensler, T. W. (2001) Sensitivity to carcinogenesis is increased and chemoprotective efficacy of enzyme inducers is lost in Nrf2 transcription factor-deficient mice. Proc. Natl. Acad. Sci. U.S.A. 98, 3410-3415.
4. Iida, K., Itoh, K., Kumagai, Y., Oyasu, R., Hattori, K., Kawai, K., Shimazui, T., Akaza, H., and Yamamoto, M. (2004) Nrf2 is essential for the chemopreventive efficacy of oltipraz against urinary bladder carcinogenesis. Cancer Res. 64, 6424-6431.
5. 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.
6. Umemura, T., Kuroiwa, Y., Kitamura, Y., Ishii, Y., Kanki, K., Kodama, Y., Itoh, K., Yamamoto, M., Nishikawa, A., and Hirose, M. (2006) A crucial role of Nrf2 in in vivo defense against oxidative damage by an environmental pollutant, pentachlorophenol. Toxicol. Sci. 90, 111-119.
7. Aoki, Y., Sato, H., Nishimura, N., Takahashi, S., Itoh, K., and Yamamoto, M. (2001) Accelerated DNA adduct formation in the lung of the Nrf2 knockout mouse exposed to diesel exhaust. Toxicol. Appl. Pharmacol. 173, 154-160.
8. Nguyen, T., Sherratt, P. J., Huang, H.-C., Yang, C. S., and Pickett, C. B. (2003) Increased protein stability as a mechanism that enhances Nrf2-mediated transcriptional activation of the antioxidant response element. Degradation of Nrf2 by the 26 S proteasome. J. Biol. Chem. 278, 4536-4541.
9. Velichkova, M., and Hasson, T. (2005) Keap1 regulates the oxidation-sensitive shuttling of Nrf2 into and out of the nucleus via a Crm1-dependent nuclear export mechanism. Mol. Cell. Biol. 25, 4501-4513.
10. 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.
11. 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.
12. Talalay, P., De Long, M. J., and Prochaska, H. J. (1988) Identification of a common chemical signal regulating the induction of enzymes that protect against chemical carcinogenesis. Proc. Natl. Acad. Sci. U.S.A. 85, 8261-8265.
13. 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.
14. 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.
15. Sakurai, T., Kanayama, M., Shibata, T., Itoh, K., Kobayashi, A., Yamamoto, M., and Uchida, K. (2006) Ebselen, a seleno-organic antioxidant, as an electrophile. Chem. Res. Toxicol. 19, 1196-1204.
16. 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.
17. 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.
18. Hong, F., Freeman, M. L., and Liebler, D. C. (2005) Identification of sensor cysteines in human Keap1 modified by the cancer chemopreventive agent sulforaphane. Chem. Res. Toxicol. 18, 1917-1926.
19. Satoh, T., Okamoto, S. i., Cui, J., Watanabe, Y., Furuta, K., Suzuki, M., Tohyama, K., and Lipton, S. A. (2006) From the cover: Activation of the Keap1/Nrf2 pathway for neuroprotection by electrophillic phase II inducers. Proc. Natl. Acad. Sci. U.S.A. 103, 768-773.
20. Gao, L., Wang, J., Sekhar, K. R., Yin, H., Yared, N. F., Schneider, S. N., Sasi, S., Dalton, T. P., Anderson, M. E., Chan, J. Y., Morrow, J. D., and Freeman, M. L. (2007) Novel n-3 fatty acid oxidation products activate Nrf2 by destabilizing the association between Keap1 and Cullin3. J. Biol. Chem. 282, 2529-2537.
21. Luo, Y., Eggler, A. L., Liu, D., Liu, G., Mesecar, A. D., and van Breemen, R. B. (2007) Sites of alkylation of human Keap1 by natural chemoprevention agents. J. Am. Soc. Mass Spectrom., in press.