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蛋白-蛋白相互作用和翻译后修饰对过氧化物酶体增殖物激活受体γ转录活性的调节。

Modulation of the transcriptional activity of peroxisome proliferator-activated receptor gamma by protein-protein interactions and post-translational modifications.

机构信息

Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea.

出版信息

Yonsei Med J. 2013 May 1;54(3):545-59. doi: 10.3349/ymj.2013.54.3.545.

Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ) belongs to a nuclear receptor superfamily; members of which play key roles in the control of body metabolism principally by acting on adipose tissue. Ligands of PPARγ, such as thiazolidinediones, are widely used in the treatment of metabolic syndromes and type 2 diabetes mellitus (T2DM). Although these drugs have potential benefits in the treatment of T2DM, they also cause unwanted side effects. Thus, understanding the molecular mechanisms governing the transcriptional activity of PPARγ is of prime importance in the development of new selective drugs or drugs with fewer side effects. Recent advancements in molecular biology have made it possible to obtain a deeper understanding of the role of PPARγ in body homeostasis. The transcriptional activity of PPARγ is subject to regulation either by interacting proteins or by modification of the protein itself. New interacting partners of PPARγ with new functions are being unveiled. In addition, post-translational modification by various cellular signals contributes to fine-tuning of the transcriptional activities of PPARγ. In this review, we will summarize recent advancements in our understanding of the post-translational modifications of, and proteins interacting with, PPARγ, both of which affect its transcriptional activities in relation to adipogenesis.

摘要

过氧化物酶体增殖物激活受体 γ(PPARγ)属于核受体超家族;其成员主要通过作用于脂肪组织,在控制机体代谢中发挥关键作用。PPARγ 的配体,如噻唑烷二酮类,广泛用于治疗代谢综合征和 2 型糖尿病(T2DM)。尽管这些药物在治疗 T2DM 方面具有潜在益处,但它们也会引起不良反应。因此,了解调控 PPARγ 转录活性的分子机制对于开发新的选择性药物或具有较少副作用的药物至关重要。分子生物学的最新进展使我们能够更深入地了解 PPARγ 在机体稳态中的作用。PPARγ 的转录活性可通过与相互作用的蛋白或蛋白本身的修饰来调节。具有新功能的 PPARγ 的新相互作用伙伴正在被揭示。此外,各种细胞信号的翻译后修饰有助于精细调节 PPARγ 的转录活性。在这篇综述中,我们将总结我们对 PPARγ 的翻译后修饰及其相互作用蛋白的理解的最新进展,这些进展均与脂肪生成有关,影响其转录活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c412/3635639/fee597e40f7f/ymj-54-545-g001.jpg

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