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Sumoylation increases HIF-1alpha stability and its transcriptional activity.

http://www.ncbi.nlm.nih.gov/pubmed/15465032

HIF-1 is closely involved in various biological processes, including angiogenesis, energy metabolism, and cell survival. HIF-1 consists of an oxygen-sensitive HIF-1alpha and oxygen-insensitive HIF-1beta. Oxygen-sensitive HIF-1alpha is subjected to post-translational modifications such as hydroxylation, ubiquitination, and acetylation, which are related to the regulation of its stability. In this present study, we found that the ectopic expression of SUMO-1 increased HIF-1alpha stability by the co-transfection study with HIF-1alpha and SUMO-1. Furthermore, the ectopic expression of SUMO-1 enhanced the transcriptional activity of HIF-1alpha. In the subsequent immunoprecipitation assay, SUMO-1 was co-immunoprecipitated with HIF-1alpha, implying that HIF-1alpha is covalently modified by SUMO-1. Thereafter, using a series of lysine mutants in the ODD domain, we found that HIF-1alpha was sumoylated at Lys(391) and Lys(477), suggesting that sumoylation at these two lysine residues enhances HIF-1alpha stability by possibly modulating other post-translational modifications. Altogether, we demonstrate that HIF-1alpha is upregulated through SUMO-1 modification at Lys(391)/Lys(477) residues, which may stabilize HIF-1alpha and enhance its transcriptional activity.

Pubmed ID: 15465032 RIS Download

Mesh terms: Amino Acid Sequence | Animals | Enzyme Stability | Gene Expression Regulation, Enzymologic | HeLa Cells | Humans | Hypoxia-Inducible Factor 1, alpha Subunit | Lysine | Molecular Sequence Data | Protein Processing, Post-Translational | SUMO-1 Protein | Transcription Factors | Transcription, Genetic