Park E J, Schroen D J, Yang M, Li H, Li L, Chen J D
Departments of Pharmacology and Molecular Toxicology, Molecular Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3519-24. doi: 10.1073/pnas.96.7.3519.
SMRT (silencing mediator for retinoid and thyroid hormone receptors) and N-CoR (nuclear receptor copressor) mediate transcriptional repression of important regulators that are involved in many signaling pathways. SMRT and N-CoR are related proteins that form complexes with mSin3A/B and histone deacetylases to induce local chromatin condensation and transcriptional repression. However, SMRT is substantially smaller than N-CoR, lacking an N-terminal domain of approximately 1,000 aa that are present in N-CoR. Here, we report the identification of SMRT-extended (SMRTe), which contains an N-terminal sequence that shows striking similarity with N-CoR. As in N-CoR, this SMRTe-N-terminal domain also represses basal transcription. We find that SMRTe expression is regulated during cell cycle progression and SMRTe transcripts are present in many embryonic tissues. These data redefine a structurally and functionally more related nuclear receptor corepressor family and suggest an additional role for SMRTe in the regulation of cycle-specific gene expression in diverse signaling pathways.
视黄酸和甲状腺激素受体沉默介质（SMRT）及核受体共抑制因子（N-CoR）介导参与多种信号通路的重要调节因子的转录抑制。SMRT和N-CoR是相关蛋白，它们与mSin3A/B及组蛋白去乙酰化酶形成复合物，以诱导局部染色质浓缩和转录抑制。然而，SMRT比N-CoR小得多，缺少N-CoR中存在的约1000个氨基酸的N端结构域。在此，我们报告了SMRT延伸蛋白（SMRTe）的鉴定，其包含与N-CoR具有显著相似性的N端序列。与N-CoR一样，这个SMRTe-N端结构域也抑制基础转录。我们发现SMRTe的表达在细胞周期进程中受到调控，且SMRTe转录本存在于许多胚胎组织中。这些数据重新定义了一个在结构和功能上更相关的核受体共抑制因子家族，并表明SMRTe在多种信号通路中对细胞周期特异性基因表达的调控中具有额外作用。
