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

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

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  • 1Institute of Signalling, Developmental Biology and Cancer Research, University of Nice, CNRS UMR 6543, Centre A. Lacassagne, 33 Avenue Valombrose, 06189 Nice, France.


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.

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