缺氧诱导因子-1和缺氧诱导因子-2:结构、功能及调节

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

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。

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.