组蛋白去乙酰化酶3：走上SMRT-N-CoR介导的基因沉默之路

HDAC3: taking the SMRT-N-CoRrect road to repression.

作者信息

Karagianni P, Wong J

机构信息

Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

出版信息

Oncogene. 2007 Aug 13;26(37):5439-49. doi: 10.1038/sj.onc.1210612.

DOI:10.1038/sj.onc.1210612

PMID:17694085

Abstract

Known histone deacetylases (HDACs) are divided into different classes, and HDAC3 belongs to Class I. Through forming multiprotein complexes with the corepressors SMRT and N-CoR, HDAC3 regulates the transcription of a plethora of genes. A growing list of nonhistone substrates extends the role of HDAC3 beyond transcriptional repression. Here, we review data on the composition, regulation and mechanism of action of the SMRT/N-CoR-HDAC3 complexes and provide several examples of nontranscriptional functions, to illustrate the wide variety of physiological processes affected by this deacetylase. Furthermore, we discuss the implication of HDAC3 in cancer, focusing on leukemia. We conclude with some thoughts about the potential therapeutic efficacies of HDAC3 activity modulation.

摘要

已知的组蛋白去乙酰化酶（HDACs）分为不同类别，HDAC3属于I类。通过与共抑制因子SMRT和N-CoR形成多蛋白复合物，HDAC3调节众多基因的转录。越来越多的非组蛋白底物清单扩展了HDAC3在转录抑制之外的作用。在这里，我们综述了关于SMRT/N-CoR-HDAC3复合物的组成、调节和作用机制的数据，并提供了几个非转录功能的例子，以说明这种去乙酰化酶影响的多种生理过程。此外，我们讨论了HDAC3在癌症中的意义，重点是白血病。我们最后思考了HDAC3活性调节的潜在治疗效果。