SUMOylation of hypoxia-inducible factor-1alpha reduces its transcriptional activity.

Article Details

Citation

Berta MA, Mazure N, Hattab M, Pouyssegur J, Brahimi-Horn MC

SUMOylation of hypoxia-inducible factor-1alpha reduces its transcriptional activity.

Biochem Biophys Res Commun. 2007 Aug 31;360(3):646-52. Epub 2007 Jun 27.

PubMed ID
17610843 [ View in PubMed
]
Abstract

The hypoxic response of mammalian cells is controlled through a transcriptional pathway that is mediated by the hypoxia-inducible factor (HIF). Here, we show that HIF-1alpha undergoes post-translational modification by the three isoforms of the small ubiquitin-related modifier (SUMO-1, -2 and -3) in vitro in proximity to and within the oxygen-dependent degradation domain (ODDD). SUMO conjugation is promoted in vitro by the E3 SUMO ligase RanBP2/Nup538 and SUMO modification in vivo does not change HIF-1alpha turnover rate. Using cotransfection of siRNA targeted to endogenous HIF-1alpha together with HIF-1alpha siRNA-resistant expression vectors carrying mutations for SUMO modification we demonstrate increased hypoxia-response element-dependent transcriptional activity for SUMO-deficient HIF-1alpha. These results indicate that when HIF-1alpha is conjugated to SUMO its transcriptional activity is decreased and that this is not mediated by a change in the protein's half-life.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Hypoxia-inducible factor 1-alphaQ16665Details