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

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.