title: Proteasomal regulation of nuclear receptor corepressor-mediated repression.
abstract: Repression of gene transcription is a fundamental property of nuclear hormone receptors. We report here that cell-specific repression by nuclear receptors correlates with levels of nuclear receptor corepressor (N-CoR) protein. N-CoR protein levels are regulated by mSiah2, a mammalian homolog of Drosophila Seven in absentia that targets N-CoR for proteasomal degradation. mSiah2 expression is cell-type specific and differentially regulates the repressive activities of nuclear receptors. These findings establish targeted proteolysis of transcriptional coregulators as a mechanism for cell-specific regulation of gene transcription.
authors.affiliation: Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: M G
authors.initials: MG
authors.lastname: Guenther
authors.forename: R W
authors.initials: RW
authors.lastname: Carthew
authors.forename: M A
authors.initials: MA
authors.lastname: Lazar
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004330:Drosophila / Q000737:chemistry; D005057:Eukaryotic Cells / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D006868:Hydrolysis; D009097:Multienzyme Complexes / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D056971:Nuclear Receptor Co-Repressor 1; D046988:Proteasome Endopeptidase Complex; D011994:Recombinant Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic / Q000235:genetics; D015533:Transcriptional Activation; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins
chemical_list: D009097:Multienzyme Complexes; C539127:NCOR1 protein, human; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D011994:Recombinant Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex