Cezanne (OTUD7B) regulates HIF-1α homeostasis in a proteasome-independent manner

Anja Bremm; Sonia Moniz; Julia Mader; Sonia Rocha; David Komander

doi:10.15252/embr.201438850

Cezanne (OTUD7B) regulates HIF-1α homeostasis in a proteasome-independent manner

Anja Bremm (Lead / Corresponding author), Sonia Moniz, Julia Mader, Sonia Rocha (Lead / Corresponding author), David Komander (Lead / Corresponding author)

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Abstract

The transcription factor HIF-1α is essential for cells to rapidly adapt to low oxygen levels (hypoxia). HIF-1α is frequently deregulated in cancer and correlates with poor patient prognosis. Here, we demonstrate that the deubiquitinase Cezanne regulates HIF-1α homeostasis. Loss of Cezanne decreases HIF-1α target gene expression due to a reduction in HIF-1α protein levels. Surprisingly, although the Cezanne-regulated degradation of HIF-1α depends on the tumour suppressor pVHL, hydroxylase and proteasome activity are dispensable. Our data suggest that Cezanne is essential for HIF-1α protein stability and that loss of Cezanne stimulates HIF-1α degradation via proteasome-independent routes, possibly through chaperone-mediated autophagy.

Original language	English
Pages (from-to)	1268-1277
Number of pages	10
Journal	EMBO Reports
Volume	15
Issue number	12
DOIs	https://doi.org/10.15252/embr.201438850
Publication status	Published - 1 Dec 2014

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License: This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Submitted manuscript, 825 KBLicence: CC BY

Strategic Award: Wellcome Trust Technology Platform
Blow, J. (Investigator), Lamond, A. (Investigator) & Owen-Hughes, T. (Investigator)
1/01/13 → 30/09/18
Project: Research

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title = "Cezanne (OTUD7B) regulates HIF-1α homeostasis in a proteasome-independent manner",

abstract = "The transcription factor HIF-1α is essential for cells to rapidly adapt to low oxygen levels (hypoxia). HIF-1α is frequently deregulated in cancer and correlates with poor patient prognosis. Here, we demonstrate that the deubiquitinase Cezanne regulates HIF-1α homeostasis. Loss of Cezanne decreases HIF-1α target gene expression due to a reduction in HIF-1α protein levels. Surprisingly, although the Cezanne-regulated degradation of HIF-1α depends on the tumour suppressor pVHL, hydroxylase and proteasome activity are dispensable. Our data suggest that Cezanne is essential for HIF-1α protein stability and that loss of Cezanne stimulates HIF-1α degradation via proteasome-independent routes, possibly through chaperone-mediated autophagy.",

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AU - Rocha, Sonia

AU - Komander, David

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AB - The transcription factor HIF-1α is essential for cells to rapidly adapt to low oxygen levels (hypoxia). HIF-1α is frequently deregulated in cancer and correlates with poor patient prognosis. Here, we demonstrate that the deubiquitinase Cezanne regulates HIF-1α homeostasis. Loss of Cezanne decreases HIF-1α target gene expression due to a reduction in HIF-1α protein levels. Surprisingly, although the Cezanne-regulated degradation of HIF-1α depends on the tumour suppressor pVHL, hydroxylase and proteasome activity are dispensable. Our data suggest that Cezanne is essential for HIF-1α protein stability and that loss of Cezanne stimulates HIF-1α degradation via proteasome-independent routes, possibly through chaperone-mediated autophagy.

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DO - 10.15252/embr.201438850

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ER -

Cezanne (OTUD7B) regulates HIF-1α homeostasis in a proteasome-independent manner

Abstract

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Strategic Award: Wellcome Trust Technology Platform

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