Sang Youzhou, Yan Fan, Ren Xiubao
Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
National Clinical Research Center of Cancer, Tianjin, China.
Oncotarget. 2015 Dec 15;6(40):42590-602. doi: 10.18632/oncotarget.6052.
CRLs (Cullin-RING E3 ubiquitin ligases) are the largest E3 ligase family in eukaryotes, which ubiquitinate a wide range of substrates involved in cell cycle regulation, signal transduction, transcriptional regulation, DNA damage response, genomic integrity, tumor suppression and embryonic development. CRL4 E3 ubiquitin ligase, as one member of CRLs family, consists of a RING finger domain protein, cullin4 (CUL4) scaffold protein and DDB1-CUL4 associated substrate receptors. The CUL4 subfamily includes two members, CUL4A and CUL4B, which share extensively sequence identity and functional redundancy. Aberrant expression of CUL4 has been found in a majority of tumors. Given the significance of CUL4 in cancer, understanding its detailed aspects of pathogenesis of human malignancy would have significant value for the treatment of cancer. Here, the work provides an overview to address the role of CRL4 E3 ubiquitin ligase in cancer development and progression, and discuss the possible mechanisms of CRL4 ligase involving in many cellular processes associated with tumor. Finally, we discuss its potential value in cancer therapy.
Cullin-RING E3泛素连接酶（CRLs）是真核生物中最大的E3连接酶家族，可泛素化多种参与细胞周期调控、信号转导、转录调控、DNA损伤反应、基因组完整性、肿瘤抑制和胚胎发育的底物。CRL4 E3泛素连接酶作为CRLs家族的一员，由一个环状结构域蛋白、cullin4（CUL4）支架蛋白和DDB1-CUL4相关底物受体组成。CUL4亚家族包括两个成员，CUL4A和CUL4B，它们具有广泛的序列同一性和功能冗余性。在大多数肿瘤中都发现了CUL4的异常表达。鉴于CUL4在癌症中的重要性，了解其在人类恶性肿瘤发病机制中的详细情况对癌症治疗具有重要价值。在此，这项工作提供了一个概述，以阐述CRL4 E3泛素连接酶在癌症发生和发展中的作用，并讨论CRL4连接酶参与许多与肿瘤相关细胞过程的可能机制。最后，我们讨论了其在癌症治疗中的潜在价值。
