期刊
EMBO REPORTS
卷 15, 期 12, 页码 1268-1277出版社
WILEY
DOI: 10.15252/embr.201438850
关键词
Cezanne; HIF-1; hypoxia; Lys11-linked ubiquitin chains; ubiquitin
资金
- Medical Research Council
- German Research Foundation (DFG)
- DFG (Emmy Noether Programme)
- Cancer Research UK
- Wellcome Trust [097945/Z/11/Z]
- Medical Research Council [U105192732]
- European Research Council [309756]
- Lister Institute for Preventive Medicine
- EMBO Young Investigator Program
- Cancer Research UK [12918] Funding Source: researchfish
- Medical Research Council [MC_U105192732] Funding Source: researchfish
- MRC [MC_U105192732] Funding Source: UKRI
- Wellcome Trust [097945/Z/11/Z] Funding Source: Wellcome Trust
The transcription factor HIF-1 is essential for cells to rapidly adapt to low oxygen levels (hypoxia). HIF-1 is frequently deregulated in cancer and correlates with poor patient prognosis. Here, we demonstrate that the deubiquitinase Cezanne regulates HIF-1 homeostasis. Loss of Cezanne decreases HIF-1 target gene expression due to a reduction in HIF-1 protein levels. Surprisingly, although the Cezanne-regulated degradation of HIF-1 depends on the tumour suppressor pVHL, hydroxylase and proteasome activity are dispensable. Our data suggest that Cezanne is essential for HIF-1 protein stability and that loss of Cezanne stimulates HIF-1 degradation via proteasome-independent routes, possibly through chaperone-mediated autophagy.
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