Gene Review:
Keap1 - kelch-like ECH-associated protein 1
Mus musculus
Synonyms:
Cytosolic inhibitor of Nrf2, INRF2, INrf2, Inrf2, Kelch-like ECH-associated protein 1, ...
- Purification, crystallization and preliminary X-ray diffraction analysis of the Kelch-like motif region of mouse Keap1. Padmanabhan, B., Scharlock, M., Tong, K.I., Nakamura, Y., Kang, M.I., Kobayashi, A., Matsumoto, T., Tanaka, A., Yamamoto, M., Yokoyama, S. Acta Crystallograph. Sect. F Struct. Biol. Cryst. Commun. (2005)
- Nrf2-Keap1 defines a physiologically important stress response mechanism. Motohashi, H., Yamamoto, M. Trends in molecular medicine. (2004)
- Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation. Wakabayashi, N., Itoh, K., Wakabayashi, J., Motohashi, H., Noda, S., Takahashi, S., Imakado, S., Kotsuji, T., Otsuka, F., Roop, D.R., Harada, T., Engel, J.D., Yamamoto, M. Nat. Genet. (2003)
- Cell Survival Responses to Environmental Stresses Via the Keap1-Nrf2-ARE Pathway. Kensler, T.W., Wakabayashi, N., Biswal, S. Annu. Rev. Pharmacol. Toxicol. (2007)
- Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Itoh, K., Wakabayashi, N., Katoh, Y., Ishii, T., Igarashi, K., Engel, J.D., Yamamoto, M. Genes Dev. (1999)
- Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer. Padmanabhan, B., Tong, K.I., Ohta, T., Nakamura, Y., Scharlock, M., Ohtsuji, M., Kang, M.I., Kobayashi, A., Yokoyama, S., Yamamoto, M. Mol. Cell (2006)
- Keap1 recruits Neh2 through binding to ETGE and DLG motifs: characterization of the two-site molecular recognition model. Tong, K.I., Katoh, Y., Kusunoki, H., Itoh, K., Tanaka, T., Yamamoto, M. Mol. Cell. Biol. (2006)
- Nrf2-Keap1 Signaling Pathway Regulates Human UGT1A1 Expression in Vitro and in Transgenic UGT1 Mice. Yueh, M.F., Tukey, R.H. J. Biol. Chem. (2007)
- Scaffolding of Keap1 to the actin cytoskeleton controls the function of Nrf2 as key regulator of cytoprotective phase 2 genes. Kang, M.I., Kobayashi, A., Wakabayashi, N., Kim, S.G., Yamamoto, M. Proc. Natl. Acad. Sci. U.S.A. (2004)
- Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants. Dinkova-Kostova, A.T., Holtzclaw, W.D., Cole, R.N., Itoh, K., Wakabayashi, N., Katoh, Y., Yamamoto, M., Talalay, P. Proc. Natl. Acad. Sci. U.S.A. (2002)
- Keap1 regulates the oxidation-sensitive shuttling of Nrf2 into and out of the nucleus via a Crm1-dependent nuclear export mechanism. Velichkova, M., Hasson, T. Mol. Cell. Biol. (2005)
- Small Maf proteins serve as transcriptional cofactors for keratinocyte differentiation in the Keap1-Nrf2 regulatory pathway. Motohashi, H., Katsuoka, F., Engel, J.D., Yamamoto, M. Proc. Natl. Acad. Sci. U.S.A. (2004)
- Keap1 regulates both cytoplasmic-nuclear shuttling and degradation of Nrf2 in response to electrophiles. Itoh, K., Wakabayashi, N., Katoh, Y., Ishii, T., O'Connor, T., Yamamoto, M. Genes Cells (2003)
- Modifying specific cysteines of the electrophile-sensing human Keap1 protein is insufficient to disrupt binding to the Nrf2 domain Neh2. Eggler, A.L., Liu, G., Pezzuto, J.M., van Breemen, R.B., Mesecar, A.D. Proc. Natl. Acad. Sci. U.S.A. (2005)
- Protection against electrophile and oxidant stress by induction of the phase 2 response: fate of cysteines of the Keap1 sensor modified by inducers. Wakabayashi, N., Dinkova-Kostova, A.T., Holtzclaw, W.D., Kang, M.I., Kobayashi, A., Yamamoto, M., Kensler, T.W., Talalay, P. Proc. Natl. Acad. Sci. U.S.A. (2004)
- Oxidative and electrophilic stresses activate Nrf2 through inhibition of ubiquitination activity of Keap1. Kobayashi, A., Kang, M.I., Watai, Y., Tong, K.I., Shibata, T., Uchida, K., Yamamoto, M. Mol. Cell. Biol. (2006)
- Hepatocyte-specific deletion of the keap1 gene activates Nrf2 and confers potent resistance against acute drug toxicity. Okawa, H., Motohashi, H., Kobayashi, A., Aburatani, H., Kensler, T.W., Yamamoto, M. Biochem. Biophys. Res. Commun. (2006)
- Activation of hepatic Nrf2 in vivo by acetaminophen in CD-1 mice. Goldring, C.E., Kitteringham, N.R., Elsby, R., Randle, L.E., Clement, Y.N., Williams, D.P., McMahon, M., Hayes, J.D., Itoh, K., Yamamoto, M., Park, B.K. Hepatology (2004)
- Keap1, the sensor for electrophiles and oxidants that regulates the phase 2 response, is a zinc metalloprotein. Dinkova-Kostova, A.T., Holtzclaw, W.D., Wakabayashi, N. Biochemistry (2005)
- Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress. Zhang, D.D., Hannink, M. Mol. Cell. Biol. (2003)
- Prothymosin-alpha mediates nuclear import of the INrf2/Cul3 Rbx1 complex to degrade nuclear Nrf2. Niture, S.K., Jaiswal, A.K. J. Biol. Chem. (2009)
- Chemoprevention through the Keap1-Nrf2 signaling pathway by phase 2 enzyme inducers. Kwak, M.K., Wakabayashi, N., Kensler, T.W. Mutat. Res. (2004)