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深入了解后期促进复合体/细胞周期体(APC/C):从细胞功能到疾病与治疗

Insights into APC/C: from cellular function to diseases and therapeutics.

作者信息

Zhou Zhuan, He Mingjing, Shah Anil A, Wan Yong

机构信息

Department of Cell Biology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Hillman Cancer Center, HCC2.6c, Pittsburgh, PA 15213 USA.

Department of Cell Biology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Hillman Cancer Center, HCC2.6c, Pittsburgh, PA 15213 USA ; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041 Sichuan People's Republic of China.

出版信息

Cell Div. 2016 Jul 13;11:9. doi: 10.1186/s13008-016-0021-6. eCollection 2016.

Abstract

Anaphase-promoting complex/cyclosome (APC/C) is a multifunctional ubiquitin-protein ligase that targets different substrates for ubiquitylation and therefore regulates a variety of cellular processes such as cell division, differentiation, genome stability, energy metabolism, cell death, autophagy as well as carcinogenesis. Activity of APC/C is principally governed by two WD-40 domain proteins, Cdc20 and Cdh1, in and beyond cell cycle. In the past decade, the results based on numerous biochemical, 3D structural, mouse genetic and small molecule inhibitor studies have largely attracted our attention into the emerging role of APC/C and its regulation in biological function, human diseases and potential therapeutics. This review will aim to summarize some recently reported insights into APC/C in regulating cellular function, connection of its dysfunction with human diseases and its implication of therapeutics.

摘要

后期促进复合物/细胞周期体(APC/C)是一种多功能泛素蛋白连接酶,它靶向不同的底物进行泛素化,从而调节多种细胞过程,如细胞分裂、分化、基因组稳定性、能量代谢、细胞死亡、自噬以及致癌作用。APC/C的活性主要由两种WD-40结构域蛋白Cdc20和Cdh1在细胞周期内外进行调控。在过去十年中,基于大量生化、三维结构、小鼠遗传学和小分子抑制剂研究的结果,极大地吸引了我们对APC/C在生物功能、人类疾病和潜在治疗中的新作用及其调控的关注。本综述旨在总结一些最近报道的关于APC/C在调节细胞功能、其功能障碍与人类疾病的关联以及其治疗意义方面的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59ff/4944252/6d706a275bab/13008_2016_21_Fig1_HTML.jpg

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