多种翻译后修饰对低氧诱导因子-1α稳定性调控的机制

Mechanism of Multiple Posttranslational Modifications in Regulation of the Stability of Hypoxia-inducible Factor-1α

低氧诱导因子-1(hypoxia-inducible factor-1,HIF-1)是组织细胞对缺氧感应和调控的一类关键转录因子,在机体中广泛表达.作为细胞低氧应答反应中的重要调节因子,HIF-1能够调节100多种涉及低氧应激下细胞适应和存活的靶基因.HIF-1是由氧依赖的α亚基和细胞内稳定表达的β亚基构成的异源二聚体.其中α亚基对氧浓度变化敏感,是HIF-1的功能性亚基,它的表达活性决定了HIF-1的生物学活性.近期研究发现,HIF-1α的一系列翻译后修饰可改变其稳定性,进而调控其转录激活活性,从而参与肿瘤、低氧性肺动脉高压以及心血管疾病等的发生与发展.本文主要就HIF-1α的一列系翻译后修饰,如羟基化、泛素化、磷酸化、乙酰化、SUMO化修饰作一综述.

Hypoxia-inducible factor-1（HIF-1）,which ubiquitously expressed in organism,is a major transcription factor of cellular response and adaptation to hypoxia.As a crucial regulator in cellular response to stress of hypoxia,HIF-1 modulates the expression of more than 100 target genes involved in cellular adaptation and survival under hypoxia stress.It is a heterodimeric that consists of an oxygen-dependent α subunit and a constitutively expressed β subunit.The α subunit,the expression of which is sensitive in respose to the variation of oxygen concentration,is the functional subunit and determines the activity of HIF-1.Recent findings showed that multiple posttranslational modifications of HIF-1α could regulate its stability,and alter the transactivational activity of HIF-1α,thereby involved in the occurrence and development of many diseases such as tumors,hypoxic pulmonary artery hypertension and cardiovascular diseases.This review summarized the ways of multiple posttranslational modifications of HIF-1α,such as hydroxynation,polyubiquitination,acetylation,phosphorylation and SUMOylation.