CSB protein is (a direct target of HIF-1 and) a critical mediator of the hypoxic response. - Archive ouverte HAL Access content directly
Journal Articles EMBO Journal Year : 2008

CSB protein is (a direct target of HIF-1 and) a critical mediator of the hypoxic response.

(1) , (1) , (2) , (1) , (3) , (1)
1
2
3

Abstract

Cockayne syndrome (CS) is a rare genetic disease characterized by neurological problems, growth failure and premature ageing. Many of these features cannot simply be ascribed to the defect that CS cells display during transcription-coupled repair. Here, we show that CSB mutant cells are unable to react to hypoxic stimuli by properly activating the hypoxia-inducible factor-1 (HIF-1) pathway, a defect that is further enhanced in the event of a concomitant genotoxic stress. Furthermore, we show that CSB expression is under the control of HIF-1 and has a critical function during hypoxic response by redistributing p300 between HIF-1 and p53. Altogether, our data demonstrate that CSB is part of a feedback loop mechanism that modulates the biological functions of p53. The outcome of this study provides new insights into the understanding of the molecular basis of the CS phenotype and the involvement of the CSB protein in the hypoxic response pathway.

Dates and versions

inserm-00350757 , version 1 (03-02-2009)

Identifiers

Cite

Silvia Filippi, Paolo Latini, Mattia Frontini, Fabrizio Palitti, Jean-Marc Egly, et al.. CSB protein is (a direct target of HIF-1 and) a critical mediator of the hypoxic response.. EMBO Journal, 2008, 27 (19), pp.2545-56. ⟨10.1038/emboj.2008.180⟩. ⟨inserm-00350757⟩
141 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More