《生命科学》 2011, 23(8): 753-761

缺氧诱导因子-1和缺氧诱导因子-2：结构、功能及调节

姚　青¹，李　筠¹，张　鹏¹，卢　玲^1*，段存明^1，2

(1 中国海洋大学医药学院分子医学生物学实验室，青岛 266003；2 Department of Molecular， Cellular and Developmental Biology， University of Michigan， Ann Arbor， Michigan 48109)

摘　要：摘　要：缺氧诱导因子-1(HIF-1)和缺氧诱导因子-2(HIF-2)是细胞应对缺氧时关键的转录因子，在生物体生理及病理过程中有重要的作用。HIF由一个α亚基和一个β亚基组成二聚体。在蛋白水平上，HIF的稳定性及转录活性受到多种机制的调控，除为人所熟知的O2/PHDs/pVHL降解途径及FIH-1羟基化作用外，分别针对HIF-1α和HIF-2α的特异性调控机制也相继被报道。从HIF-1α和HIF-2α的蛋白结构、稳定性调控、转录激活功能以及两者在细胞代谢、肿瘤发生中的作用等方面对两者的相似性和差异性进行综述。
关键词：HIF-1α；HIF-2α；调控；转录活性；细胞代谢；肿瘤发生

Hypoxia inducible factor (HIF)-1 and -2: structure， function， and regulation

YAO Qing¹， LI Yun¹， ZHANG Peng¹， LU Ling^1*， DUAN Cun-Ming^1，2

(1 School of Medicine and Pharmacy， Ocean University of China， Qingdao 266003， China; 2 Department of Molecular， Cellular and Developmental Biology， University of Michigan， Ann Arbor， Michigan 48109， USA)

Abstract: Abstract: Hypoxia inducible factor-1 (HIF-1) and HIF-2 are crucial transcription factors mediating cellular response to hypoxia， which play important roles in a variety of physiological and pathological states in organisms. HIF proteins compose of an oxygen-dependent α-subunit and a constitutively expressed β-subunit. The levels of HIF-α， ranging from gene transcription to protein stability， is regulated by several mechanisms. Among these regulatory mechanisms， the O2/PHDs/pVHL degradation pathway and FIH-1 mediating hydroxylation are well investigated and understood. Recent reports suggest that other factors also regulate the levels of HIF-α. Some of these factors are unique to HIF-1α or HIF-2α. In this review， we compare and contrast the commonalities and differences of HIF-1α and HIF-2α in protein structure， regulation of protein stability， and function. Furthermore， we summarize the known biological actions of HIF， including their roles in cellular metabolism and tumor genesis.
Key words: HIF-1α; HIF-2α; regulation; transcriptional activity; cellular metabolism; tumor genesis