The role and mechanism of CRL4 E3 ubiquitin ligase in cancer and its potential therapy implications.
The role and mechanism of CRL4 E3 ubiquitin ligase in cancer and its potential therapy implications.
复制标题
CRL4 E3 泛素连接酶在癌症中的作用和机制及其潜在的治疗意义。
DOI：
10.18632/oncotarget.6052
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发表时间：
2015-12-15
期刊：
影响因子：
--
通讯作者：
Ren X
中科院分区：
文献类型：
--
作者：
Sang Y;Yan F;Ren X
CRL是真核生物中最大的E3连接酶家族，广泛参与细胞周期调控、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。CRL4 E3泛素连接酶是CRLS家族的成员之一，由环指结构域蛋白、CUL4支架蛋白和DDB1-CUL4相关底物受体组成。CUL4亚家族包括CUL4A和CUL4B两个成员，它们具有广泛的序列同源性和功能冗余。在大多数肿瘤中发现了CUL4的异常表达。鉴于CUL4在癌症中的重要意义，了解其在人类恶性肿瘤发病机制中的详细作用对于癌症的治疗具有重要的价值。本文综述了CRL4 E3泛素连接酶在肿瘤发生发展中的作用，并探讨了CRL4连接酶参与肿瘤相关细胞过程的可能机制。最后，我们讨论了它在癌症治疗中的潜在价值。
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.