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核激素受体抑制复合物的一个共抑制因子及潜在组分的克隆与特性分析

Cloning and characterization of a corepressor and potential component of the nuclear hormone receptor repression complex.

作者信息

Zamir I, Dawson J, Lavinsky R M, Glass C K, Rosenfeld M G, Lazar M A

机构信息

Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

出版信息

Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14400-5. doi: 10.1073/pnas.94.26.14400.

Abstract

Nuclear hormone receptors are potent repressors of transcription in the unliganded state. We describe here the cloning of a nuclear receptor corepressor that we call SUN-CoR (Small Unique Nuclear receptor CoRepressor), which shows no homology to previously described nuclear hormone receptor corepressors, N-CoR, or SMRT. SUN-CoR is a highly basic, 16-kDa nuclear protein that is expressed at high levels in adult tissues and is induced during adipocyte and myogenic differentiation. SUN-CoR potentiates transcriptional repression by thyroid hormone receptor and RevErb in vivo, represses transcription when fused to a heterologous DNA binding domain, and interacts with RevErb as well as with thyroid hormone receptor in vitro. SUN-CoR also interacts with N-CoR and SMRT in vitro and with endogenous N-CoR in cells. We conclude that SUN-CoR is a corepressor and may function as an additional component of the complex involved in transcriptional repression by unliganded and orphan nuclear hormone receptors.

摘要

核激素受体在未结合配体状态下是转录的强效抑制因子。我们在此描述一种核受体共抑制因子的克隆,我们将其称为SUN-CoR(小的独特核受体共抑制因子),它与先前描述的核激素受体共抑制因子N-CoR或SMRT没有同源性。SUN-CoR是一种高度碱性的16 kDa核蛋白,在成年组织中高水平表达,并在脂肪细胞和成肌细胞分化过程中被诱导。SUN-CoR在体内增强甲状腺激素受体和RevErb的转录抑制作用,当与异源DNA结合结构域融合时抑制转录,并在体外与RevErb以及甲状腺激素受体相互作用。SUN-CoR在体外也与N-CoR和SMRT相互作用,并在细胞中与内源性N-CoR相互作用。我们得出结论,SUN-CoR是一种共抑制因子,可能作为未结合配体的孤儿核激素受体参与转录抑制的复合物的额外组分发挥作用。

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