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FBW7泛素连接酶:细胞分裂、生长与分化交汇点上的一种肿瘤抑制因子

FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiation.

作者信息

Welcker Markus, Clurman Bruce E

机构信息

Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109, USA.

出版信息

Nat Rev Cancer. 2008 Feb;8(2):83-93. doi: 10.1038/nrc2290.

Abstract

FBW7 (F-box and WD repeat domain-containing 7) is the substrate recognition component of an evolutionary conserved SCF (complex of SKP1, CUL1 and F-box protein)-type ubiquitin ligase. SCF(FBW7) degrades several proto-oncogenes that function in cellular growth and division pathways, including MYC, cyclin E, Notch and JUN. FBW7 is also a tumour suppressor, the regulatory network of which is perturbed in many human malignancies. Numerous cancer-associated mutations in FBW7 and its substrates have been identified, and loss of FBW7 function causes chromosomal instability and tumorigenesis. This Review focuses on structural and functional aspects of FBW7 and its role in the development of cancer.

摘要

FBW7(含F-box和WD重复结构域7)是进化保守的SCF(SKP1、CUL1和F-box蛋白复合物)型泛素连接酶的底物识别成分。SCF(FBW7)降解几种在细胞生长和分裂途径中起作用的原癌基因,包括MYC、细胞周期蛋白E、Notch和JUN。FBW7也是一种肿瘤抑制因子,其调控网络在许多人类恶性肿瘤中受到干扰。已鉴定出FBW7及其底物中许多与癌症相关的突变,FBW7功能丧失会导致染色体不稳定和肿瘤发生。本综述重点关注FBW7的结构和功能方面及其在癌症发展中的作用。

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