HIF-1α的泛素化和SUMO化修饰

Ubiquitinational and SUMOylational Modification of Alpha Subunit of HIF-1

低氧诱导因子-1(hypoxia-inducible factor-1,HIF-1)是异二聚体的转录因子,由氧敏感的α亚基和在细胞内稳定表达的β亚基组成,在细胞低氧应答反应中起核心作用,能调节100多种涉及低氧应激下细胞适应和存活的靶基因.泛素是一种由76个氨基酸残基组成的保守性多肽,广泛存在真核生物中.SUMO是泛素样蛋白家族成员,分子量约为12 kD的小蛋白,从拟南芥到人类普遍存在.泛素和SUMO可共价结合许多靶底物蛋白,对其进行翻译后修饰,该过程分别称为泛素化与SUMO化.近来研究显示,HIF-1α的翻译后修饰如泛素化、SUMO化可调节其的稳定性,从而改变HIF-1α的转录激活活性.本文主要就HIF-1α泛素化及SUMO化修饰等问题作一综述.

The hypoxia-inducible factor-1（HIF-1） is a heterodimeric transcription factor composed of an oxygen-sensitive α subunit and a constitutively expressed β subunit,which plays a crucial role in cellular response to stress of hypoxia.HIF-1α modulates the expression of more than 100 genes involved in cellular adaptation and survival under hypoxic stress.Ubiquitin is an evolutionarily conserved 76-residue polypeptide among eukaryotes.However,small ubiquitin-related modifier（SUMO）,a small protein about 12 kD,is structurally related to ubiquitin and widely expressed from Arabidopsis thaliana to Homo sapiens.Both ubiquitin and SUMO belong to members of the ubiqutin-like proteins and act as post-translational modification.The process that both ubiquitin and SUMO covalently attach to proteins is known as ubiquitination and SUMOylation,respectively.Recent studies have showed that ubiquitination and SUMOylation of HIF-1α regulate its stability,leading to altered transactivational activity of HIF-1α.This review aims to summarise current advances in modification of HIF-1α,involving ubiquitination and SUMOylation.