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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
49
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pubmed:dateCreated |
2006-12-4
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pubmed:abstractText |
Keap1 is a BTB-Kelch substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex that functions as a sensor for thiol-reactive chemopreventive compounds and oxidative stress. Inhibition of Keap1-dependent ubiquitination of the bZIP transcription factor Nrf2 enables Nrf2 to activate a cyto-protective transcriptional program that counters the damaging effects of oxidative stress. In this report we have identified a member of the phosphoglycerate mutase family, PGAM5, as a novel substrate for Keap1. The N terminus of the PGAM5 protein contains a conserved NXESGE motif that binds to the substrate binding pocket in the Kelch domain of Keap1, whereas the C-terminal PGAM domain binds Bcl-X(L). Keap1-dependent ubiquitination of PGAM5 results in proteasome-dependent degradation of PGAM5. Quinone-induced oxidative stress and the chemopreventive agent sulforaphane inhibit Keap1-dependent ubiquitination of PGAM5. The identification of PGAM5 as a novel substrate of Keap1 suggests that Keap1 regulates both transcriptional and post-transcriptional responses of mammalian cells to oxidative stress.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
8
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pubmed:volume |
281
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
37893-903
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pubmed:dateRevised |
2008-6-19
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pubmed:meshHeading |
pubmed-meshheading:17046835-Amino Acid Motifs,
pubmed-meshheading:17046835-Amino Acid Sequence,
pubmed-meshheading:17046835-Animals,
pubmed-meshheading:17046835-Binding Sites,
pubmed-meshheading:17046835-COS Cells,
pubmed-meshheading:17046835-Cell Cycle Proteins,
pubmed-meshheading:17046835-Cell Line,
pubmed-meshheading:17046835-Cercopithecus aethiops,
pubmed-meshheading:17046835-Humans,
pubmed-meshheading:17046835-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:17046835-Molecular Sequence Data,
pubmed-meshheading:17046835-Oxidation-Reduction,
pubmed-meshheading:17046835-Phylogeny,
pubmed-meshheading:17046835-Recombinant Proteins,
pubmed-meshheading:17046835-Sequence Homology, Amino Acid,
pubmed-meshheading:17046835-Substrate Specificity,
pubmed-meshheading:17046835-Transfection,
pubmed-meshheading:17046835-Ubiquitin-Protein Ligases,
pubmed-meshheading:17046835-bcl-X Protein
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pubmed:year |
2006
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pubmed:articleTitle |
PGAM5, a Bcl-XL-interacting protein, is a novel substrate for the redox-regulated Keap1-dependent ubiquitin ligase complex.
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pubmed:affiliation |
Department of Biochemistry, University of Missouri, Columbia, Missouri 65211, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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