Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex.
作者： Donna D. Zhang , Shih-Ching Lo , Janet V. Cross , Dennis J. Templeton , Mark Hannink
DOI: 10.1128/MCB.24.24.10941-10953.2004
关键词:
摘要: The bZIP transcription factor Nrf2 controls a genetic program that protects cells from oxidative damage and maintains cellular redox homeostasis. Keap1, BTB-Kelch protein, is the major upstream regulator of both subcellular localization steady-state levels Nrf2. In this report, we demonstrate Keap1 functions as substrate adaptor protein for Cul3-dependent E3 ubiquitin ligase complex. assembles into functional complex with Cul3 Rbx1 targets multiple lysine residues located in N-terminal Neh2 domain conjugation vivo vitro. Keap1-dependent ubiquitination inhibited following exposure to quinone-induced stress sulforaphane, cancer-preventive isothiocyanate. A mutant containing single cysteine-to-serine substitution at residue 151 within BTB markedly resistant inhibition by either or sulforaphane. Inhibition correlates decreased association Cul3. Neither nor sulforaphane disrupts between Our results suggest ability assemble critical determinant response compounds stress.
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sci-hub.se 参考文章(62)
J. Harper, N. Pavletich, B. Schulman, P. Jeffrey, G. Wu, G. Xu, STRUCTURE OF A BETA-TRCPI-SKP1-BETA-CATENIN COMPLEX: DESTRUCTION MOTIF BINDING AND LYSINE SPECIFICITY OF THE SCF(BETA-TRCP1) UBIQUITIN LIGASE Molecules and Cells. ,vol. 6, ,(2003)
Barry Halliwell, Okezie I. Aruoma, DNA and free radicals Ellis Horwood. ,(1993)
Pascale Bomont, Laurent Cavalier, François Blondeau, Christiane Ben Hamida, Samir Belal, Meriem Tazir, Ercan Demir, Haluk Topaloglu, Rudolf Korinthenberg, Beyhan Tüysüz, Pierre Landrieu, Fayçal Hentati, Michel Koenig, The gene encoding gigaxonin, a new member of the cytoskeletal BTB/kelch repeat family, is mutated in giant axonal neuropathy Nature Genetics. ,vol. 26, pp. 370- 374 ,(2000) , 10.1038/81701
Gregory A Cope, Raymond J Deshaies, COP9 signalosome: a multifunctional regulator of SCF and other cullin-based ubiquitin ligases. Cell. ,vol. 114, pp. 663- 671 ,(2003) , 10.1016/S0092-8674(03)00722-0
C. Roland Wolf, Ken Itoh, Colin J. Henderson, Masayuki Yamamoto, Simon A. Chanas, Michael McMahon, Christophe Cavin, Lesley I. McLellan, John D. Hayes, 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 Research. ,vol. 61, pp. 3299- 3307 ,(2001)
Cecile M. Pickart, Mechanisms underlying ubiquitination. Annual Review of Biochemistry. ,vol. 70, pp. 503- 533 ,(2001) , 10.1146/ANNUREV.BIOCHEM.70.1.503
Tamara R. Golden, Douglas A. Hinerfeld, Simon Melov, Oxidative stress and aging: beyond correlation Aging Cell. ,vol. 1, pp. 117- 123 ,(2002) , 10.1046/J.1474-9728.2002.00015.X
Andy Y. Shih, Delinda A. Johnson, Gloria Wong, Andrew D. Kraft, Lei Jiang, Heidi Erb, Jeffrey A. Johnson, Timothy H. Murphy, Coordinate Regulation of Glutathione Biosynthesis and Release by Nrf2-Expressing Glia Potently Protects Neurons from Oxidative Stress The Journal of Neuroscience. ,vol. 23, pp. 3394- 3406 ,(2003) , 10.1523/JNEUROSCI.23-08-03394.2003
Nobunao Wakabayashi, Ken Itoh, Junko Wakabayashi, Hozumi Motohashi, Shuhei Noda, Satoru Takahashi, Sumihisa Imakado, Tomoe Kotsuji, Fujio Otsuka, Dennis R Roop, Takanori Harada, James Douglas Engel, Masayuki Yamamoto, Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation Nature Genetics. ,vol. 35, pp. 238- 245 ,(2003) , 10.1038/NG1248
Hozumi Motohashi, Tania O'Connor, Fumiki Katsuoka, James Douglas Engel, Masayuki Yamamoto, Integration and diversity of the regulatory network composed of Maf and CNC families of transcription factors. Gene. ,vol. 294, pp. 1- 12 ,(2002) , 10.1016/S0378-1119(02)00788-6