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 nuc lear receptors correlates with levels of nuclear receptor corepressor (N-CoR) protein. N-CoR protein levels are regulated by mSiah2, a mamma lian homolog of Drosophila Seven in absentia that targets N-CoR for pr oteasomal degradation. mSiah2 expression is cell-type specific and dif ferentially regulates the repressive activities of nuclear receptors. These findings establish targeted proteolysis of transcriptional coreg ulators as a mechanism for cell-specific regulation of gene transcript ion.