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[Bcl-2 家族蛋白的生理功能与结构基础]

[Physiological Function and Structural Basis of Bcl-2 Family Proteins].

作者信息

健愉 冯, 玉山 朱, 陈 权, 凌 林家, Jianyu Feng, Yushan Zhu, Quan Chen, Jialing Lin

机构信息

, 300074.

, 73126-0901.

出版信息

Zhongguo Xi Bao Sheng Wu Xue Xue Bao. 2019 Aug;41(8):1477-1489. Epub 2019 Sep 12.

Abstract

Apoptosis is an important biological process that plays a key role in the regulation of cell fate and homeostasis. The B-cell lymphoma-2 (Bcl-2) family proteins are important regulators of the apoptotic pathway, and their dysfunction is associated with a variety of diseases, including cancer, neurodegenerative and autoimmune diseases. In the past decade, a large number of research work on the physiological functions and atomic structures of Bcl-2 family proteins have been reported, which has deepened our understanding of the molecular mechanism and pathological significance of Bcl-2 family proteins. Recently, new drugs targeting different Bcl-2 proteins have been developed and used in clinics or tested in clinical trials. However, the complexity and diversity in functions and structures of Bcl-2 family have left many unsolved problems. This article summarizes current knowledge of the structure and function of Bcl-2 family proteins and discusses the pharmacological significance of Bcl-2 proteins as effective therapeutic targets.

摘要

细胞凋亡是一种重要的生物学过程,在细胞命运调控和内环境稳态中发挥关键作用。B细胞淋巴瘤-2(Bcl-2)家族蛋白是细胞凋亡途径的重要调节因子,其功能失调与多种疾病相关,包括癌症、神经退行性疾病和自身免疫性疾病。在过去十年中,已报道了大量关于Bcl-2家族蛋白生理功能和原子结构的研究工作,这加深了我们对Bcl-2家族蛋白分子机制和病理意义的理解。最近,针对不同Bcl-2蛋白的新药已被开发出来,并应用于临床或正在进行临床试验。然而,Bcl-2家族在功能和结构上的复杂性和多样性仍留下许多未解决的问题。本文总结了目前关于Bcl-2家族蛋白结构和功能的知识,并讨论了Bcl-2蛋白作为有效治疗靶点的药理学意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8056/8265309/03100abafea0/nihms-1063538-f0002.jpg

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本文引用的文献

1
BCL-2 family protein BOK is a positive regulator of uridine metabolism in mammals.BCL-2 家族蛋白 BOK 是哺乳动物尿苷代谢的正调控因子。
Proc Natl Acad Sci U S A. 2019 Jul 30;116(31):15469-15474. doi: 10.1073/pnas.1904523116. Epub 2019 Jul 16.
2
Bok regulates mitochondrial fusion and morphology.Bok 调节线粒体融合和形态。
Cell Death Differ. 2019 Dec;26(12):2682-2694. doi: 10.1038/s41418-019-0327-4. Epub 2019 Apr 11.
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Small-molecule allosteric inhibitors of BAX.BAX 的小分子别构抑制剂。
Nat Chem Biol. 2019 Apr;15(4):322-330. doi: 10.1038/s41589-018-0223-0. Epub 2019 Feb 4.
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Topology of active, membrane-embedded Bax in the context of a toroidal pore.活性、膜嵌入 Bax 的拓扑结构在环形孔的情况下。
Cell Death Differ. 2018 Nov;25(10):1717-1731. doi: 10.1038/s41418-018-0184-6. Epub 2018 Sep 5.
7
MIM through MOM: the awakening of Bax and Bak pores.通过 MOM 的 MIM:Bax 和 Bak 孔的觉醒。
EMBO J. 2018 Sep 3;37(17). doi: 10.15252/embj.2018100340. Epub 2018 Aug 22.

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