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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 summarize the molecular basis of ubiquitinated degradation of hypoxia inducible factor 1 (HIF-1) and tumor-related biological effects, and the ubiquitin proteasome pathway, and to elucidate the mechanism of HIF-1 deubiquitination Research progress. Methods: Using PubMed and CNKI full-text database retrieval system, HIF-1, ubiquitination and proteasome were used as keywords to search the relevant literature from 2005 to 2012. Inclusion criteria: 1) the structure and biological effects of HIF; 2) the ubiquitin proteasome pathway; and 3) the mechanism by which ubiquitination of HIF occurs. 30 articles meeting the requirements for inclusion in the analysis. Results: Hypoxia is a common phenomenon in most tumor formation. HIF-1 is a transcriptional activator induced by hypoxia and promotes the proliferation, invasion and metastasis of tumor cells. Ubiquitin proteasome pathway is the main way HIF-1 degradation, the degradation is divided into two types of oxygen-dependent and oxygen-independent ubiquitin proteasome pathway. HIF-1 α subunit exists in oxygen-dependent degradation zone, when the ambient oxygen concentration> 5%, by activating the ubiquitin-proteasome pathway, HIF-1α rapid degradation. Hypoxia-related factors can cause HIF-1α independent of oxygen ubiquitination and degradation by the proteasomal pathway. Conclusion: HIF-1 can promote the proliferation and invasion of tumor cells. The study on the mechanism of HIF-1 degradation by ubiquitin proteasome can provide a scientific basis for tumor therapy.