乏氧诱导因子结构、表达及调控

Structure, Expression and Regulation of Hypoxia-inducible Factor

乏氧诱导因子(HIF)是乏氧应答中起重要作用的转录因子,一直是乏氧研究的焦点.HIF由α亚基和β亚基组成,α亚基包括HIF-1α、HIF-2α和HIF-3α,其中α亚基因诱导条件不同通过选择性剪接产生不同变体.β亚基包括ARNT、ARNT2和ARNT3.α与β亚基在乏氧等应激反应时形成二聚体HIF启动靶基因转录表达,参与多种细胞生物学功能的调控.目前为止,大多数的研究都集中于野生型HIF-1α,对它的结构、表达调控及其调控做了相对全面而清楚的了解.后来通过多种策略及方法,陆续发现并克隆出了除HIF-1α外的HIF各亚基.研究不再局限于HIF-1α,而是扩展至HIF整个系统,如相继发现的HIF-2α和HIF-3α亚基,以及它们的变体,对HIF-1α的研究也更深入了,但是关于HIF-1α的变体、HIF-2α、HIF-3α及β亚基的表达调控及功能还不明确,是未来研究的方向.本文全面介绍HIF的最新研究进展,阐述HIF各亚基的结构、表达调控及其靶基因的表达情况.

Hypoxia-inducible factor （HIF） is an important transcriptional factor, which plays crucial role in response to hypoxia. HIF consists of a subunit and β subunit, a subunit contains HIF-1α, HIF-2α and HIF-3α, and β subunit include aryl hydrocarbon receptor nuclear translocator（ARNT）, ARNT2 and ARNT3α. a subunit produces different variants by mRNA alternative splicing in different environments. HIF-α and HIF-β subunits form heterodimeric HIF, and then induce target genes transcription and expression, which regulate various biological functions. To date, most of researches focus on wide type HIF-1α. Later, HIF-2α, HIF-3α and their variants have been discovered and cloned by various strategies and methods. The study of HIF is not only limited to HIF-1α, but also expanded to the whole HIF system. HIF-1α was elucidated more widely, however, the expression regulation and function of HIF-2α, HIF-3α, HIF-β and their variants are still not clear, which are needed future study. This review aim to cover these issues in light of recent advances in HIF research, involving structure, expression regulation and target genes of every subunit of HIF.