کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1937266 | 1050712 | 2007 | 7 صفحه PDF | دانلود رایگان |

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-1α 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-1α turnover rate. Using cotransfection of siRNA targeted to endogenous HIF-1α together with HIF-1α siRNA-resistant expression vectors carrying mutations for SUMO modification we demonstrate increased hypoxia-response element-dependent transcriptional activity for SUMO-deficient HIF-1α. These results indicate that when HIF-1α is conjugated to SUMO its transcriptional activity is decreased and that this is not mediated by a change in the protein’s half-life.
Journal: Biochemical and Biophysical Research Communications - Volume 360, Issue 3, 31 August 2007, Pages 646–652