人类和小鼠核受体共抑制因子SMRT的独特形式。
Unique forms of human and mouse nuclear receptor corepressor SMRT.
作者信息
Ordentlich P, Downes M, Xie W, Genin A, Spinner N B, Evans R M
机构信息
Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
出版信息
Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2639-44. doi: 10.1073/pnas.96.6.2639.
Abstract
Nuclear hormone receptors have been shown to repress transcription in the absence of ligand. This repression is mediated by a corepressor complex that contains the Sin3A protein and histone deacetylases (HDAC1 and 2). Studies by several groups demonstrate that this complex is recruited to nuclear receptors through the highly related corepressors SMRT (silencing mediator of retinoid acid and thyroid hormone receptor) and N-CoR (nuclear receptor corepressor). We describe here the cloning, characterization, and chromosomal mapping of forms of human and mouse SMRT that includes a 1,000-aa extension, which reveals striking homology to the amino terminus of N-CoR. Structure and function studies of wild-type and natural splicing variants suggest the presence of 3-4 amino terminal domains that repress in a cooperative as well as mechanistically distinct fashion.
摘要
核激素受体已被证明在没有配体的情况下会抑制转录。这种抑制是由一种共抑制复合物介导的，该复合物包含Sin3A蛋白和组蛋白脱乙酰酶（HDAC1和2）。几个研究小组的研究表明，这种复合物通过高度相关的共抑制因子SMRT（视黄酸和甲状腺激素受体沉默介质）和N-CoR（核受体共抑制因子）被招募到核受体上。我们在此描述了人和小鼠SMRT形式的克隆、表征及染色体定位，其包括一个1000个氨基酸的延伸，该延伸与N-CoR的氨基末端具有显著同源性。对野生型和天然剪接变体的结构和功能研究表明，存在3 - 4个氨基末端结构域，它们以协同以及机制上不同的方式发挥抑制作用。
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