药学学报, 2021, 56(11): 2908-2915
引用本文:
兰月娇, 程明涵, 高建*. S期激酶相关蛋白2在纤维化疾病中的作用机制研究进展[J]. 药学学报, 2021, 56(11): 2908-2915.
LAN Yue-jiao, CHENG Ming-han, GAO Jian*. Research progress on the mechanisms of S-phase kinase-associated protein 2 in fibrotic diseases[J]. Acta Pharmaceutica Sinica, 2021, 56(11): 2908-2915.

S期激酶相关蛋白2在纤维化疾病中的作用机制研究进展
兰月娇, 程明涵, 高建*
大连医科大学附属第二医院, 辽宁 大连 116023
摘要:
S期激酶相关蛋白2 (Skp2) 是E3泛素连接酶的组成部分之一,其通过将K48与K63连接的泛素链连接到不同的底物上,起到诱导蛋白酶体介导的蛋白水解或调节标记底物发挥促进细胞增殖与迁移、抑制细胞凋亡与衰老等作用。Skp2是多种纤维化疾病潜在的药物作用靶标,在多种纤维化疾病中呈现高表达,且调控疾病的发生发展。本文在介绍Skp2的归属、结构、下游靶标以及细胞机制调控的基础上,重点阐述Skp2在多种纤维化疾病如肝纤维化、特发性肺纤维化、肾纤维化、角膜纤维化和心脏纤维化中的研究进展,以期为临床开发靶向Skp2的纤维化治疗药物提供新的研究思路。
关键词:    S期激酶相关蛋白2      p27      纤维化疾病      细胞增殖      细胞衰老     
Research progress on the mechanisms of S-phase kinase-associated protein 2 in fibrotic diseases
LAN Yue-jiao, CHENG Ming-han, GAO Jian*
The Second Affiliated Hospital, Dalian Medical University, Dalian 116023, China
Abstract:
S-phase kinase-associated protein 2 (Skp2) is one of the components of E3 ubiquitin ligase, which can induce proteasome-mediated proteolysis or regulate labeled substrates to promote cell proliferation and migration and inhibit cell apoptosis and senescence by connecting the ubiquitin chains of K48 and K63 to different substrates. Skp2 is also a potential drug target in a variety of fibrotic diseases, is highly expressed in a variety of fibrotic diseases, and regulates the occurrence and progression of these diseases. This paper reviews Skp2's structure, downstream targets, and cellular regulation and then focuses on research progress on Skp2 in various fibrotic diseases, such as liver fibrosis, idiopathic pulmonary fibrosis, renal fibrosis, corneal fibrosis, and cardiac fibrosis, which may help provide a new research approaches for clinical development of Skp2-targeted antifibrotic drugs.
Key words:    Skp2    p27    fibrotic disease    cell proliferation    cell senescence   
收稿日期: 2021-06-11
DOI: 10.16438/j.0513-4870.2021-0863
基金项目: 国家自然科学基金资助项目(81973637,81473267,81274172).
通讯作者: 高建,Tel/Fax:86-411-84670304,E-mail:gaojianayfy@163.com
Email: gaojianayfy@163.com
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