Lv Yi, Xiao Jia, Liu Jing, Xing Feiyue
Department of Immunobiology, Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou, China.
Key Laboratory of Functional Protein Research of Guangdong, Higher Education Institutes, Jinan University, Guangzhou, China.
J Cancer. 2017 Apr 9;8(7):1205-1213. doi: 10.7150/jca.18255. eCollection 2017.
E2F transcriptional factors are widely expressed in a number of tissues and organs, possessing many regulatory functions related to cellular proliferation, differentiation, DNA repair, cell-cycle and cell apoptosis. E2F8 is a recently identified member of the E2F family with a duplicated DNA-binding domain feature discriminated from E2F1-6, controlling gene expression in a dimerization partner-independent manner. It is indispensable for angiogenesis, lymphangiogenesis and embryonic development. Although E2F8 and E2F7 perform complementary and overlapping functions in many cell metabolisms, E2F8, but not E2F7, overexpresses remarkably in hepatocellular carcinoma (HCC) to facilitate the HCC occurrence and development activating a E2F1/ Cyclin D1 signaling pathway to regulate the G1- to S-phase transition of cell cycle progression or transcriptionally suppressing CDK1 to induce hepatocyte polyploidization. It also involves closely a variety of cellular physiological functions and pathological processes, which may bring a new breakthrough for the treatment of certain diseases, especially the HCC. Here, we summarize the latest progress of E2F8 on its relevant functions and mechanisms as well as potential application.
E2F转录因子在许多组织和器官中广泛表达,具有许多与细胞增殖、分化、DNA修复、细胞周期和细胞凋亡相关的调节功能。E2F8是E2F家族中最近发现的成员,具有与E2F1-6不同的重复DNA结合结构域特征,以不依赖二聚化伙伴的方式控制基因表达。它对血管生成、淋巴管生成和胚胎发育必不可少。尽管E2F8和E2F7在许多细胞代谢中发挥互补和重叠的功能,但E2F8而非E2F7在肝细胞癌(HCC)中显著过表达,以促进HCC的发生和发展,激活E2F1/细胞周期蛋白D1信号通路来调节细胞周期进程从G1期到S期的转变,或转录抑制CDK1以诱导肝细胞多倍体化。它还密切涉及多种细胞生理功能和病理过程,这可能为某些疾病,尤其是HCC的治疗带来新的突破。在此,我们总结了E2F8在其相关功能、机制以及潜在应用方面的最新进展。