Hypoxia-inducible factors: Crosstalk between their protein stability and protein degradation

As a transcription factor family dependent of oxygen, hypoxia-inducible factors (HIFs) play important roles in organic and cellular homeostasis, which are master regulators of tumorigenesis, angiogenesis and embryogenesis. Up to date, some known posttranslational modifications, such as hydroxylation, acetylation, phosphorylation and S-nitrosylation, have been proved to influence protein stability and transcriptional activity of HIFs. On the other hand, HIFs can be physiologically degraded through ubiquitin-dependent or -independent proteasome pathway. Two biochemical processes involve in many modulators, which are correlated and compose an intricate mechanism to control the biological function of HIFs systemically. Herein, we review and discuss the diverse roles of involved modulators in both HIFs stability and degradation, describe the potential link between the two molecular scenarios. (C) 2007 Elsevier Ireland Ltd. All rights reserved.