低氧诱导因子-1：细胞适应氧供应改变的关键蛋白  

Hypoxia-inducible Factor-1: a Key Protein for Cells Adapting to Changes in Oxygen Supply

作　　者：梁楚婷 郭炜骅 谭理 贺筠博 熊芳[1,2] 张姗姗[1] 曾朝阳[1,2] 熊炜 李桂源[1,2] 郭灿 LIANG Chu-Ting;GUOWei-Hua;TAN Li;HE Yun-Bo;XIONG Fang;ZHANG Shan-Shan;ZENG Zhao-Yang;XIONGWei;LI Gui-Yuan;GUO Can(Department of Ophthalmology,Xiangya Hospital,Central South University,Changsha 410008,China;NHC Key Laboratory of Carcinogenesis and Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education,Cancer Research Institute,Central South University,Changsha 410008,China)

机构地区：[1]中南大学湘雅医院口腔科,长沙410008 [2]中南大学肿瘤研究所,国家卫健委癌变原理重点实验室和教育部癌变与侵袭原理重点实验室,长沙410008

出　　处：《生物化学与生物物理进展》2019年第11期1041-1049,共9页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金（81672993,81772928,81702907,81772901,81803025）;湖南省自然科学基金（2018JJ3704,2018JJ3815,2018SK21210,2018SK21211）资助项目~~

摘　　要：2019年诺贝尔生理学或医学奖授予威廉·凯林(William Kaelin Jr)、彼得·拉特克里夫爵士(Sir Peter Ratcliffe)和格雷格·赛门扎(Gregg Semenza),以表彰他们在细胞感知和适应缺氧机制上做出的重要贡献.低氧诱导因子-1(hypoxiainducible factor-1,HIF-1)在细胞适应氧供应改变中起关键作用,可作为转录因子改变基因表达,通过提高机体携氧能力、增加血液供应、改变代谢方式等途径来适应缺氧环境.而HIF-1的功能也受到各种机制调控:泛素化-蛋白酶体途径降解和转录因子活性抑制.HIF-1与抑癌蛋白(protein von Hippel-Lindau,pVHL)、脯氨酸羟化酶(proline hydroxylase,PHD)、HIF抑制因子(factor inhibiting HIF,FIH)等构成了严密有序的调节网络.本文总结了3位诺贝尔奖获得者的研究成果,并结合最新的研究进展,系统阐述了HIF-1表达量调节机制和HIF-1介导的细胞适应缺氧环境机制.In 2019,the Nobel Prize in Physiology or Medicine was awarded to William G.Kaelin Jr,Sir Peter J.Ratcliffe and Gregg L.Semenza for their discoveries in mechanism of how cells sense and adapt to oxygen level.Hypoxia-inducible factor-1(HIF-1)plays a key role in this mechanism.It can act as a transcription factor to alter gene expression and adapt to hypoxia by increasing oxygen carrying capacity,increasing blood supply,and changing metabolic patterns.The function of HIF-1 is also regulated by various mechanisms:ubiquitinationproteasome pathway degradation and inhibition of transcription factor activity under the action of tumor suppressor proteins pVHL,proline hydroxylase(PHD),factor inhibiting HIF(FIH),etc.This paper summarizes the research results of three Nobel Prize winners,and introduces the latest progress,systematically expounds the regulation mechanism of HIF-1 and HIF-1 mediated cell adaptation to hypoxia.

关 键 词：低氧诱导因子-1 缺氧 EPO VEGF VHL PHD FIH 

分 类 号：Q2[生物学—细胞生物学] Q5