Hypoxia-Inducible Factors (HIFs) and Phosphorylation: Impact on Stability, Localization, and Transactivity

被引：142

作者：

Kietzmann, Thomas ^{[1
]}

Mennerich, Daniela ^{[1
]}

Dimova, ElitsaY. ^{[1
]}

机构：

[1] Univ Oulu, Bioctr Oulu, Fac Biochem & Mol Med, Oulu, Finland

来源：

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY | 2016年 / 4卷

基金：

芬兰科学院;

关键词：

phosphorylation; HIF-1; alpha; hypoxia; kinase; MAPK pathway; PI3K/PKB pathway; ENDOTHELIAL GROWTH-FACTOR; ACTIVATED PROTEIN-KINASE; GLYCOGEN-SYNTHASE KINASE-3; FACTOR 1-ALPHA HIF-1-ALPHA; POLO-LIKE KINASES; FACTOR-I; TRANSCRIPTIONAL ACTIVITY; MAMMALIAN TARGET; GENE-EXPRESSION; TUMOR-SUPPRESSOR;

D O I：

10.3389/fcell.2016.00011

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The hypoxia-inducible factor alpha-subunits (HIF alpha) are key transcription factors in the mammalian response to oxygen deficiency. The HIF alpha regulation in response to hypoxia occurs primarily on the level of protein stability due to posttranslational hydroxylation and proteasomal degradation. However, HIF alpha-subunits also respond to various growth factors, hormones, or cytokines under normoxia indicating involvement of different kinase pathways in their regulation. Because these proteins participate in angiogenesis, glycolysis, programmed cell death, cancer, and ischemia, HIF alpha regulating kinases are attractive therapeutic targets. Although numerous kinases were reported to regulate HIF alpha indirectly, direct phosphorylation of HIF alpha affects HIF alpha stability, nuclear localization, and transactivity. Herein, we review the role of phosphorylation-dependent HIF alpha regulation with emphasis on protein stability, subcellular localization, and transactivation.

引用

页数：14

共 163 条

[51] Thrombin activates the hypoxia-inducible factor-1 signaling pathway in vascular smooth muscle cells role of the p22phox-containing NADPH oxidase [J].