Li Jie, Xu Ying, Jiao HuiKe, Wang Wei, Mei Zhu, Chen GuoQiang
Department of Pathophysiology, Chemical Biology Division of Shanghai Universities E-Institutes, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Sci China Life Sci. 2014 Jul;57(7):657-64. doi: 10.1007/s11427-014-4685-3. Epub 2014 Jun 11.
Hypoxia-inducible factor-1 (HIF-1) is a key heterodimeric transcription factor for the cellular adaptive response to hypoxia, a common feature of the microenvironment in solid tumors. The transcriptional activity, protein stabilization, protein-protein interactions and cellular localization of HIF-1α, an oxygen-sensitive subunit of HIF-1, are mainly modulated by various post-translational modifications. Recently, we reported that polycomb chromobox 4 (Cbx4) governs the transcriptional activity of HIF-1α by enhancing its sumoylation at K391 and K477, through which Cbx4 potentiates angiogenesis of hepatocellular carcinoma. This review summarizes the current knowledge of HIF-1α sumoylation and its roles in the pathogenesis of cancer.
缺氧诱导因子-1（HIF-1）是细胞对缺氧适应性反应的关键异二聚体转录因子，而缺氧是实体瘤微环境的一个共同特征。HIF-1的氧敏感亚基HIF-1α的转录活性、蛋白质稳定性、蛋白质-蛋白质相互作用及细胞定位主要受多种翻译后修饰调控。最近，我们报道多梳蛋白染色体框4（Cbx4）通过增强HIF-1α在K391和K477位点的SUMO化修饰来调控其转录活性，借此Cbx4促进了肝细胞癌的血管生成。本综述总结了目前关于HIF-1α SUMO化修饰及其在癌症发病机制中作用的相关知识。
