中国科技核心期刊
CN:31-1600/Q
ISSN:1004-0374
“健康与疾病的免疫”国际学术研讨会通知      关于有网站冒充本刊网站的声明
《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: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 Ling1*, DUAN Cun-Ming1,2
(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: 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
 
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