Genetically engineered mouse models for functional studies of SKP1-CUL1-F-box-protein (SCF) E3 ubiquitin ligases.
Genetically engineered mouse models for functional studies of SKP1-CUL1-F-box-protein (SCF) E3 ubiquitin ligases.
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SCF（SKP 1（S-phase-kinase-associated protein 1），Cullin-1，F-box protein）E3泛素连接酶是Cullin-RING连接酶（CRL）的创始成员，是哺乳动物中最大的E3泛素连接酶家族。每个单独的SCF E3连接酶由一个衔接蛋白SKP 1、一个支架蛋白cullin-1（八个cullin的第一个家族成员）、69个家族成员中的一个F盒蛋白和两个RING（真正有趣的新基因）家族蛋白RBX 1/ROC 1或RBX 2/ROC 2/SAG/RNF 7中的一个组成。这四种成分的各种组合构建了大量的SCF E3，其以细胞环境、时间和空间依赖的方式促进许多关键调节蛋白的降解，从而精确地控制许多重要的细胞过程，包括细胞周期进展、凋亡、基因转录、信号转导、DNA复制、基因组完整性的维持和肿瘤发生。为了理解SCF E3连接酶如何在体内生理条件下调节这些细胞过程和胚胎发育，已经建立了许多具有SCF组分的转基因（Tg）表达或靶向缺失的小鼠模型并进行了表征。本文简要介绍了泛素-蛋白酶体系统（UPS）和SCF E3泛素连接酶，并对SCF E3的Tg和KO小鼠模型进行了综述，讨论了各组分在小鼠胚胎发生、细胞增殖、凋亡、癌变以及其他与人类疾病相关的致病过程中的作用。最后，我们将简要讨论这一研究领域的未来方向，以及所获得的知识在更有效的人类疾病治疗干预中的潜在应用。
The SCF (SKP1 (S-phase-kinase-associated protein 1), Cullin-1, F-box protein) E3 ubiquitin ligases, the founding member of Cullin-RING ligases (CRLs), are the largest family of E3 ubiquitin ligases in mammals. Each individual SCF E3 ligase consists of one adaptor protein SKP1, one scaffold protein cullin-1 (the first family member of the eight cullins), one F-box protein out of 69 family members, and one out of two RING (Really Interesting New Gene) family proteins RBX1/ROC1 or RBX2/ROC2/SAG/RNF7. Various combinations of these four components construct a large number of SCF E3s that promote the degradation of many key regulatory proteins in cell-context, temporally, and spatially dependent manners, thus controlling precisely numerous important cellular processes, including cell cycle progression, apoptosis, gene transcription, signal transduction, DNA replication, maintenance of genome integrity, and tumorigenesis. To understand how the SCF E3 ligases regulate these cellular processes and embryonic development under in vivo physiological conditions, a number of mouse models with transgenic (Tg) expression or targeted deletion of components of SCF have been established and characterized. In this review, we will provide a brief introduction to the ubiquitin-proteasome system (UPS) and the SCF E3 ubiquitin ligases, followed by a comprehensive overview on the existing Tg and knockout (KO) mouse models of the SCF E3s, and discuss the role of each component in mouse embryogenesis, cell proliferation, apoptosis, carcinogenesis, as well as other pathogenic processes associated with human diseases. We will end with a brief discussion on the future directions of this research area and the potential applications of the knowledge gained to more effective therapeutic interventions of human diseases.
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影响因子：
7.8
作者：
Gong B;Chen F;Pan Y;Arrieta-Cruz I;Yoshida Y;Haroutunian V;Pasinetti GM
通讯作者：
Pasinetti GM
影响因子：
64.5
作者：
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Schulman, Brenda A.
影响因子：
50.3
作者：
Barbash, Olena;Zamfirova, Petia;Lin, Douglas I.;Chen, Xiangmei;Yang, Ke;Nakagawa, Hiroshi;Lu, Fengmin;Rustgi, Anil K.;Diehl, J. Alan
通讯作者：
Diehl, J. Alan
影响因子：
16
作者：
Brownell, James E.;Sintchak, Michael D.;Dick, Lawrence R.
通讯作者：
Dick, Lawrence R.
影响因子：
64.5
作者：
Feldman, RMR;Correll, CC;Deshaies, RJ
通讯作者：
Deshaies, RJ