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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Hubbi, Maimon E. Semenza, Gregg L. Hu, Hongxia Gilkes, Daniele M. |
| Description | Author Affiliation: Hubbi ME ( Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.) |
| Abstract | Hypoxia-inducible factor (HIF) 1 and HIF-2 are heterodimeric proteins composed of an oxygen-regulated HIF-1 or HIF-2 subunit, respectively, and a constitutively expressed HIF-1ß subunit, which mediate adaptive transcriptional responses to hypoxia. Here, we report that Sirt7 (sirtuin-7) negatively regulates HIF-1 and HIF-2 protein levels by a mechanism that is independent of prolyl hydroxylation and that does not involve proteasomal or lysosomal degradation. The effect of Sirt7 was maintained in the presence of the sirtuin inhibitor nicotinamide and upon deletion or mutation of its deacetylase domain, indicating a non-catalytic function. Knockdown of Sirt7 led to an increase in HIF-1 and HIF-2 protein levels and an increase in HIF-1 and HIF-2 transcriptional activity. Thus, we identify a novel molecular function of Sirt7 as a negative regulator of HIF signaling. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 29 |
| Volume Number | 288 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2013-07-19 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Basic Helix-Loop-Helix Transcription Factors Antagonists & Inhibitors Hypoxia-Inducible Factor 1, Alpha Subunit Sirtuins Metabolism Genetics Cell Line, Tumor Down-Regulation Gene Knockdown Techniques Lysosomes Proteasome Endopeptidase Complex Protein Binding Proteolysis Transcription, Genetic Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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