Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou 510405, China.
Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, 199 Ren'ai Road, Suzhou, Jiangsu, 215123, China.
Curr Pharm Des. 2018;24(15):1676-1681. doi: 10.2174/1381612824666180528081024.
The HERC family contains six members from HERC1 to HERC6 that are featured with the HECT domains that exerts ubiquitin ligase activity and the RCC1-like domains that are involved in cell cycle regulation. Although identified as early as 1990s, their biological functions are extensively studied in recent years. More and more researches have demonstrated that the HERC ubiquitin ligases are widely engaged in carcinogenesis, however, there lacks a comprehensive and instructive analysis.
The PubMed database was searched by keywords of individual HERC proteins (such as HERC4) and cancer. The emerging roles of HERC proteins in cancer and the specific mechanisms were collectively analyzed and discussed.
HERC proteins belong to the HECT domain-containing ubiquitin ligases that can identify and mediate the ubiquitination of specific substrate proteins. All HERC ubiquitin ligases except HERC6 have been assigned one or more than one ubiquitination substrates. In all of HERCs, HERC1 and HERC2 have been widely studied, in contrast, there are no reported studies yet on protein ubiquitination mediated by HERC6. Dependent on the protein substrates, HERC proteins may act as a tumor suppressor or oncoprotein in specific cancer types. For example, HERC4 is believed to contribute to carcinogenesis of solid tumors such as lung cancer, but it suppresses the proliferation of myeloma cells.
HERC proteins as ubiquitin ligases are widely involved in various cancers. Targeting at specific HERC proteins could be a strategy for the treatment of certain cancers.
HERC 家族包含六个成员，从 HERC1 到 HERC6，它们都具有 E3 泛素连接酶活性的 HECT 结构域和参与细胞周期调控的 RCC1 样结构域。尽管早在 20 世纪 90 年代就已被发现，但近年来它们的生物学功能才得到广泛研究。越来越多的研究表明，HERC 泛素连接酶广泛参与了致癌作用，但缺乏全面而有指导意义的分析。
通过关键词（如 HERC4 等个别 HERC 蛋白）和癌症在 PubMed 数据库中进行搜索。对 HERC 蛋白在癌症中的新作用及其具体机制进行了综合分析和讨论。
HERC 蛋白属于 HECT 结构域含有泛素连接酶，可以识别和介导特定底物蛋白的泛素化。除 HERC6 外，所有 HERC 泛素连接酶都已被分配了一个或多个泛素化底物。在所有的 HERC 中，HERC1 和 HERC2 已被广泛研究，相比之下，HERC6 介导的蛋白质泛素化尚未有报道。依赖于蛋白质底物，HERC 蛋白可能在特定类型的癌症中作为肿瘤抑制因子或癌蛋白发挥作用。例如，HERC4 被认为有助于肺癌等实体瘤的致癌作用，但它抑制骨髓瘤细胞的增殖。
作为泛素连接酶的 HERC 蛋白广泛参与各种癌症。针对特定的 HERC 蛋白可能是治疗某些癌症的一种策略。
