Proteasomal regulation of nuclear receptor corepressor-mediated repression.
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.
Zhang
J
J
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Guenther
M G
MG
Carthew
R W
RW
Lazar
M A
MA
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
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