摘要
低氧诱导因子(hypoxia-inducible factor 1,HIF-1)是一种调节细胞和机体氧稳态的转录因子。在低氧时,HIF-1蛋白得以稳定,并活化一系列基因如促红细胞生成素、血管内皮生长因子、糖酵解酶等来增强细胞供能供氧能力,促使细胞在低氧环境下存活或增殖。在这一过程中,热休克蛋白90(heat shock protein 90,HSP90)对HIF-1起着重要的调节作用,它能与活化蛋白激酶C受体竞争结合HIF-1α,使其免于非氧依赖方式的降解从而维持其稳定,并影响低氧时HIF-1α的核转位、与HIF-1β的异二聚化及转录活性等。此外,HIF-1也能通过增强热休克因子的转录水平来上调热休克蛋白家族,进而加强自身的稳定。
Hypoxia inducible factor-1 （HIF-1）is a transcriptional activator that regulates cellu- 1α and systemic oxygen homeostasis. HIF-1 could be stabilized under hypoxic condition, and promote cell survival and proliferation by increasing transcription of a number of survive genes such as EPO, VEGF and glycolytic enzyme, which can enhance oxygen and energy delivery capacity under hypoxia. HSP90 plays an important role in regulating activity of HIF-1 in this process. HSP90 can compete with the receptor of activated protein kinase C （ RACK1 ） for binding to HIF-1α to make it be free of O2-independent degradation and keep stabilization. HSP90 can also affect HIF-1α＇ s nuclear translocation, dimerization with HIF-1β and binding activity with DNA. In addition, HIF-1 can increase the transcriptional level of HSF to up-regulate expression of HSPs including HSP90 which can enhance the stabilization of HIF-1α.
出处
《国际病理科学与临床杂志》
CAS
2008年第4期348-352,共5页
Journal of International Pathology and Clinical Medicine
基金
国家973项目(2006CB504100)~~
