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 Dros...

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Bibliographic Details
Published in:Genes & development 1998-06, Vol.12 (12), p.1775-1780
Main Authors: Zhang, J, Guenther, M G, Carthew, R W, Lazar, M A
Format: Article
Language:English
Subjects:
Animals
Cell Line, Transformed
Cysteine Endopeptidases - metabolism
Drosophila - chemistry
Eukaryotic Cells - cytology
Eukaryotic Cells - metabolism
Gene Expression Regulation
Humans
Hydrolysis
Multienzyme Complexes - metabolism
Nuclear Proteins - chemistry
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Nuclear Proteins - physiology
Nuclear Receptor Co-Repressor 1
Proteasome Endopeptidase Complex
Recombinant Proteins - genetics
Repressor Proteins - chemistry
Repressor Proteins - genetics
Repressor Proteins - metabolism
Repressor Proteins - physiology
Research Communication
Trans-Activators - genetics
Trans-Activators - physiology
Transcription, Genetic - genetics
Transcriptional Activation
Ubiquitin-Protein Ligases
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Summary: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.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.12.12.1775