缺氧诱导因子1降解-泛素化研究进展

Research progress in degradation of HIF-1-ubiquitination

目的:总结缺氧诱导因子1(hypoxia inducible factor 1,HIF-1)经泛素化降解的分子基础与肿瘤相关的生物学效应、泛素蛋白酶体途径,阐述HIF-1经泛素化降解的研究进展。方法:应用PubMed和CNKI期刊全文数据库检索系统,以HIF-1、泛素化、蛋白酶体为关键词,检索2005-2012年的相关文献。纳入标准:1)HIF的结构及生物学效应;2)泛素蛋白酶体途径;3)HIF经泛素化降解的机制。符合要求纳入分析的文献30篇。结果:缺氧是大多数肿瘤形成过程中普遍存在的现象,HIF-1是细胞应激缺氧时所产生的转录激活因子,可促进肿瘤细胞增殖、侵袭和转移。泛素蛋白酶体途径是HIF-1降解的主要方式,其降解分为氧依赖性和氧独立性泛素蛋白酶体途径两种。HIF-1的α亚基内存在氧依赖降解区,当环境内氧浓度>5%时,可通过激活泛素-蛋白酶体途径,使HIF-1α迅速降解。缺氧相关因子可以引起HIF-1α不依赖氧泛素化并经蛋白酶体途径降解。结论:HIF-1可以促进肿瘤细胞增殖侵袭,对HIF-1经泛素蛋白酶体系统降解机制的研究能为肿瘤治疗提供科学依据。

OBJECTIVE：To sum up the molecular basis of hypoxia inducible factor I（HIF-1） degradation via ubiquitination and its biological effect relation to tumour, Ubiquitin Proteasome pathway and research progress of HIF-1 degradation via ubiquitination. METHODS： Relevant articles were searched by ＂HIF-1, ubiquitination and proteasome＂ as keywords in PubMed and CNKI database from 2005 to 2012. Totally 30 papers were selected and analyzed according to the in- clusion criteria as follows： the structure of HIF-1 and its biological effect; Ubiquitin Proteasome pathway; the mechanism of HIF-1 degradation via ubiquitination. RESULTS： Hypoxia is a common characteristic of tumorigenesis, hypoxia-inducible factors 1 ,a transcription factor involved in the response of mammalian ceils to oxygen deprivation,has led to multiple as- pects of tumor progression,including proliferation,invasion and metastasis. HIF-1 is targeted for degradation by the ubiq- uitin-proteasome pathway of oxygen-dependent or oxygen-independent. Under normoxia condition,the HIF-1 protein is degraded by the ubiquitin-proteasome pathway through the oxygen-dependent degradation domain of HIF-1α. HAF is the key mediator of a new HIF-1α specific degradation pathway that degrades HIF-1α through a oxygen-independent mechanism. CONCLUSTION： HIF-1 has led to tumor proliferation and invasion, the research of the mechanism of HIF-1 degradation via ubiquitination could provide a foundation to oncotherapy. [