The Skp2 Pathway: A Critical Target for Cancer Therapy.
The Skp2 Pathway: A Critical Target for Cancer Therapy.
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DOI：
10.1016/j.semcancer.2020.01.013
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发表时间：
2020-12
影响因子：
14.5
通讯作者：
Lin, Hui-Kuan
中科院分区：
文献类型：
--
作者：
Cai, Zhen;Moten, Asad;Peng, Danni;Hsu, Che-Chia;Pan, Bo-Syong;Manne, Rajeshkumar;Li, Hong-yu;Lin, Hui-Kuan
由泛素-蛋白酶体系统（UPS）严格调控的蛋白质降解对各种细胞过程至关重要，其失调与包括癌症在内的严重疾病有关。Skp2是Skp2- scf E3连接酶复合物的一个很好的表征成分，能够在其不同的底物上结合k48连接的泛素链和k63连接的泛素链，分别诱导蛋白酶体介导的蛋白质水解或调节标记底物的功能。Skp2的过表达在各种人类癌症中被观察到，这些癌症与低生存率和不良治疗结果相关，这反过来表明Skp2参与致瘤活性。为此，各种遗传小鼠模型证明了Skp2的致癌特性，突出了Skp2作为治疗癌症靶点的潜力。在本文中，我们将描述Skp2的下游底物以及Skp2- scf复合物活性的上游调节因子。我们将进一步总结Skp2的综合致癌功能，同时描述目前可用于开发Skp2抑制剂的各种策略和治疗平台。
Strictly regulated protein degradation by ubiquitin-proteasome system (UPS) is essential for various cellular processes whose dysregulation is linked to serious diseases including cancer. Skp2, a well characterized component of Skp2-SCF E3 ligase complex, is able to conjugate both K48-linked ubiquitin chains and K63-linked ubiquitin chains on its diverse substrates, inducing proteasome mediated proteolysis or modulating the function of tagged substrates respectively. Overexpression of Skp2 is observed in various human cancers associated with poor survival and adverse therapeutic outcomes, which in turn suggests that Skp2 engages in tumorigenic activity. To that end, the oncogenic properties of Skp2 are demonstrated by various genetic mouse models, highlighting the potential of Skp2 as a target for tackling cancer. In this article, we will describe the downstream substrates of Skp2 as well as upstream regulators for Skp2-SCF complex activity. We will further summarize the comprehensive oncogenic functions of Skp2 while describing diverse strategies and therapeutic platforms currently available for developing Skp2 inhibitors.
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影响因子：
4.3
作者：
Appleman, Leonard J.;Chernova, Irene;Boussiotis, Vassiliki A.
通讯作者：
Boussiotis, Vassiliki A.
影响因子：
21.3
作者：
Carrano, AC;Eytan, E;Pagano, M
通讯作者：
Pagano, M
影响因子：
64.8
作者：
Bashir, T;Dorrello, NV;Pagano, M
通讯作者：
Pagano, M
影响因子：
4
作者：
Auld, Corinth A.;Caccia, Carla D.;Morrison, Ron F.
通讯作者：
Morrison, Ron F.
影响因子：
14.5
作者：
Bloom, J;Pagano, M
通讯作者：
Pagano, M