Zhang J, Guenther M G, Carthew R W, Lazar M A
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Genes Dev. 1998 Jun 15;12(12):1775-80. doi: 10.1101/gad.12.12.1775.
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.
基因转录的抑制是核激素受体的一项基本特性。我们在此报告，核受体的细胞特异性抑制与核受体共抑制因子（N-CoR）蛋白水平相关。N-CoR蛋白水平受mSiah2调控，mSiah2是果蝇“七缺失”蛋白的哺乳动物同源物，可将N-CoR靶向蛋白酶体降解。mSiah2的表达具有细胞类型特异性，并差异调节核受体的抑制活性。这些发现确立了转录共调节因子的靶向蛋白水解作为基因转录细胞特异性调节的一种机制。
