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能量稳态调控中的转录共调节因子。

Transcriptional coregulators in the control of energy homeostasis.

作者信息

Feige Jérôme N, Auwerx Johan

机构信息

Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université Louis Pasteur, Illkirch, France.

出版信息

Trends Cell Biol. 2007 Jun;17(6):292-301. doi: 10.1016/j.tcb.2007.04.001. Epub 2007 May 1.

Abstract

Metabolic programs controlling energy homeostasis are governed at the transcriptional level by the integrated action of several transcription factors. Among these, nuclear receptors including peroxisome proliferator-activated receptors, estrogen-related receptors or thyroid hormone receptors play prominent roles by adapting gene expression programs to the endocrine and metabolic context that they sense via their ligand-binding domain. Coregulators assist nuclear receptors to positively or negatively influence the transcription of target genes, and thereby comprise an integral part of the transcriptional circuitry. This review focuses on how coregulators, including PGC-1 and p160 coactivators, Sirt-1, RIP140 and NCoR corepressors, control the balance between energy storage and expenditure, with a particular emphasis on how these proteins integrate physiological stimuli in vivo. The general picture that emerges indicates that these coregulators are metabolic switches, which convergently regulate metabolic pathways through their pleiotropic interactions with nuclear receptors and other transcription factors.

摘要

控制能量稳态的代谢程序在转录水平上受多种转录因子的综合作用调控。其中,包括过氧化物酶体增殖物激活受体、雌激素相关受体或甲状腺激素受体在内的核受体,通过使其基因表达程序适应它们经由配体结合结构域所感知的内分泌和代谢环境,发挥着重要作用。共调节因子协助核受体对靶基因转录产生正向或负向影响,因此构成转录调控回路的一个组成部分。本综述聚焦于包括PGC-1和p160共激活因子、Sirt-1、RIP140和NCoR共抑制因子在内的共调节因子如何控制能量储存与消耗之间的平衡,尤其着重于这些蛋白质如何在体内整合生理刺激。所呈现的总体情况表明,这些共调节因子是代谢开关,它们通过与核受体及其他转录因子的多效性相互作用,共同调节代谢途径。

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