HIF‐1‐dependent transcriptional activity is required for oxygen‐mediated HIF‐1α degradation
Authors:
- Edurne BerraEBEdurne Berra
- Darren E RichardDRDarren E Richard
- Emmanuel GothiéEGEmmanuel Gothié
- Jacques PouysségurJPJacques Pouysségur
- 20 February 2001
- journal article
- Published by Wiley in FEBS Letters
- Vol. 491 (1-2) , 85-90
Abstract
Hypoxia‐inducible factor‐1α (HIF‐1α) plays a central role in oxygen homeostasis. In normoxia, HIF‐1α is a short lived protein, whereas hypoxia rapidly increases HIF‐1α protein levels by relaxing its ubiquitin–proteasome‐dependent degradation. In this study, we show that the p42/p44 MAP kinase cascade, known to phosphorylate HIF‐1α, does not modulate the degradation/stabilization profile of HIF‐1α. However, we present evidence that the rate of HIF‐1α degradation depends on the duration of hypoxic stress. We demonstrate that degradation of HIF‐1α is suppressed by: (i) inhibiting general transcription with actinomycin D or (ii) specifically blocking HIF‐1‐dependent transcriptional activity. In keeping with these findings, we postulate that HIF‐1α is targetted to the proteasome via a HIF‐1α proteasome targetting factor (HPTF) which expression is directly under the control of HIF‐1‐mediated transcriptional activity. Although HPTF is not yet molecularly identified, it is clearly distinct from the von Hippel–Lindau protein (pVHL).Keywords
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