TY  - JOUR
A1  - Moniz, Sonia
A1  - Bandarra, Daniel
A1  - Biddlestone, John
A1  - Campbell, Kirsteen J.
A1  - Komander, David
A1  - Bremm, Anja
A1  - Rocha, Sonia
T1  - Cezanne regulates E2F1-dependent HIF2α expression
T2  - Journal of cell science
N2  - Mechanisms regulating protein degradation ensure the correct and timely expression of transcription factors such as hypoxia inducible factor (HIF). Under normal O2 tension, HIFα subunits are targeted for proteasomal degradation, mainly through vHL-dependent ubiquitylation. Deubiquitylases are responsible for reversing this process. Although the mechanism and regulation of HIFα by ubiquitin-dependent proteasomal degradation has been the object of many studies, little is known about the role of deubiquitylases. Here, we show that expression of HIF2α (encoded by EPAS1) is regulated by the deubiquitylase Cezanne (also known as OTUD7B) in an E2F1-dependent manner. Knockdown of Cezanne downregulates HIF2α mRNA, protein and activity independently of hypoxia and proteasomal degradation. Mechanistically, expression of the HIF2α gene is controlled directly by E2F1, and Cezanne regulates the stability of E2F1. Exogenous E2F1 can rescue HIF2α transcript and protein expression when Cezanne is depleted. Taken together, these data reveal a novel mechanism for the regulation of the expression of HIF2α, demonstrating that the HIF2α promoter is regulated by E2F1 directly and that Cezanne regulates HIF2α expression through control of E2F1 levels. Our results thus suggest that HIF2α is controlled transcriptionally in a cell-cycle-dependent manner and in response to oncogenic signalling.
KW  - HIF2α
KW  - Cezanne
KW  - Hypoxia
KW  - Cell cycle
KW  - E2F1
KW  - ChIP
Y1  - 2015
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/50593
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-505935
SN  - 1477-9137
SN  - 0021-9533
N1  - © 2015. Published by The Company of Biologists Ltd
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
VL  - 128
IS  - 16
SP  - 3082
EP  - 3093
PB  - Company of Biologists Limited
CY  - Cambridge
ER  -