PMID- 18784753
OWN - NLM
STAT- MEDLINE
DCOM- 20081027
LR  - 20211020
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 27
IP  - 19
DP  - 2008 Oct 8
TI  - CSB protein is (a direct target of HIF-1 and) a critical mediator of the hypoxic 
      response.
PG  - 2545-56
LID - 10.1038/emboj.2008.180 [doi]
AB  - 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.
FAU - Filippi, Silvia
AU  - Filippi S
AD  - Laboratory of Molecular Cytogenetics and Mutagenesis, Department ABAC, University 
      of Tuscia, Viterbo, Italy.
FAU - Latini, Paolo
AU  - Latini P
FAU - Frontini, Mattia
AU  - Frontini M
FAU - Palitti, Fabrizio
AU  - Palitti F
FAU - Egly, Jean-Marc
AU  - Egly JM
FAU - Proietti-De-Santis, Luca
AU  - Proietti-De-Santis L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080911
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Poly-ADP-Ribose Binding Proteins)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.3.1.48 (p300-CBP Transcription Factors)
RN  - EC 3.6.4.- (DNA Helicases)
RN  - EC 3.6.4.12 (ERCC6 protein, human)
RN  - EC 6.5.1.- (DNA Repair Enzymes)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cell Cycle/physiology
MH  - Cell Line
MH  - Cockayne Syndrome/genetics
MH  - DNA Helicases/genetics/*metabolism
MH  - DNA Repair Enzymes/genetics/*metabolism
MH  - Gene Expression Regulation
MH  - Humans
MH  - *Hypoxia
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism
MH  - Molecular Sequence Data
MH  - Poly-ADP-Ribose Binding Proteins
MH  - RNA Interference
MH  - Signal Transduction/*physiology
MH  - Tumor Suppressor Protein p53/genetics/metabolism
MH  - Vascular Endothelial Growth Factor A/genetics/metabolism
MH  - p300-CBP Transcription Factors/genetics/metabolism
PMC - PMC2567410
EDAT- 2008/09/12 09:00
MHDA- 2008/10/28 09:00
PMCR- 2009/10/08
CRDT- 2008/09/12 09:00
PHST- 2008/05/07 00:00 [received]
PHST- 2008/08/14 00:00 [accepted]
PHST- 2008/09/12 09:00 [pubmed]
PHST- 2008/10/28 09:00 [medline]
PHST- 2008/09/12 09:00 [entrez]
PHST- 2009/10/08 00:00 [pmc-release]
AID - emboj2008180 [pii]
AID - 10.1038/emboj.2008.180 [doi]
PST - ppublish
SO  - EMBO J. 2008 Oct 8;27(19):2545-56. doi: 10.1038/emboj.2008.180. Epub 2008 Sep 11.