FEBS Letters | |
HIF‐1‐dependent transcriptional activity is required for oxygen‐mediated HIF‐1α degradation | |
Gothié, Emmanuel1  Richard, Darren E1  Berra, Edurne1  Pouysségur, Jacques1  | |
[1] Institute of Signaling, Developmental Biology and Cancer Research, CNRS-UMR 6543, Centre Antoine Lacassagne, 33 Avenue Valombrose, 06189 Nice, France | |
关键词: Hypoxia; HIF-1; Proteasome; pVHL; | |
DOI : 10.1016/S0014-5793(01)02159-7 | |
学科分类:生物化学/生物物理 | |
来源: John Wiley & Sons Ltd. | |
【 摘 要 】
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).
【 授权许可】
Unknown
【 预 览 】
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