PMID:15776016
| Citation |
Li, Z, Wang, D, Messing, EM and Wu, G (2005) VHL protein-interacting deubiquitinating enzyme 2 deubiquitinates and stabilizes HIF-1alpha. EMBO Rep. 6:373-8 |
|---|---|
| Abstract |
Hypoxia-inducible factor (HIF)-1alpha is a short-lived protein and is ubiquitinated and degraded through the von Hippel-Lindau protein (pVHL)-E3 ubiquitin ligase pathway at normoxia. Deubiquitination, by reversing ubiquitination, has been recognized as an important regulatory step in ubiquitination-related processes. Here, we show that pVHL-interacting deubiquitinating enzyme 2, VDU2, but not VDU1, interacts with HIF-1alpha. VDU2 can specifically deubiquitinate and stabilize HIF-1alpha and, therefore, increase expression of HIF-1alpha targeted genes, such as vascular endothelial growth factor (VEGF). These findings suggest that ubiquitination of HIF-1alpha is a dynamic process and that ubiquitinated HIF-1alpha might be rescued from degradation by VDU2 through deubiquitination. Although pVHL functions as a master control for HIF-1alpha stabilization, as pVHL-E3 ligase mediates the ubiquitination of both HIF-1alpha and VDU2, the balance between the pVHL-mediated ubiquitination and VDU2-mediated deubiquitination of HIF-1alpha provides another level of control for HIF-1alpha stabilization. |
| Links |
PubMed PMC1299287 Online version:10.1038/sj.embor.7400377 |
| Keywords |
Animals; COS Cells; Cercopithecus aethiops; Endopeptidases/metabolism; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation; HeLa Cells; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immunoblotting; Luciferases; Reverse Transcriptase Polymerase Chain Reaction; Transcription Factors/metabolism; Tumor Suppressor Proteins/metabolism; Ubiquitin Thiolesterase; Ubiquitin-Protein Ligases/metabolism; Ubiquitins/metabolism; Von Hippel-Lindau Tumor Suppressor Protein |
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