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p53 promotes VEGF expression and angiogenesis in the absence of an intact p21-Rb pathway

Morvarid Farhang Ghahremani, Steven Goossens UGent, D Nittner, X Bisteau, Sona Bartunkova UGent, A Zwolinska, Paco Hulpiau UGent, Katharina Haigh UGent, Lieven Haenebalcke, Benjamin Drogat UGent, et al. (2013) CELL DEATH AND DIFFERENTIATION. 20(7). p.888-897
abstract
There is growing evidence that the p53 tumour suppressor downregulates vascular endothelial growth factor (VEGF) expression, although the underlying mechanisms remain unclear and controversial. Here we provide insights from in vitro experiments and in vivo xenotransplantation assays that highlight a dual role for p53 in regulating VEGF during hypoxia. Unexpectedly, and for the first time, we demonstrate that p53 rapidly induces VEGF transcription upon hypoxia exposure by binding, in an HIF-1 alpha-dependent manner, to a highly conserved and functional p53-binding site within the VEGF promoter. However, during sustained hypoxia, p53 indirectly downregulates VEGF expression via the retinoblastoma (Rb) pathway in a p21-dependent manner, which is distinct from its role in cell-cycle regulation. Our findings have important implications for cancer therapy, especially for tumours that harbour wild-type TP53 and a dysfunctional Rb pathway.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
angiogenesis, p21, p53, VEGF, HYPOXIA-INDUCIBLE FACTOR, GROWTH-FACTOR GENE, WILD-TYPE P53, FACTOR-BINDING SITES, TUMOR ANGIOGENESIS, FACTOR 1-ALPHA, CELL-CYCLE, RETINOBLASTOMA, TRANSCRIPTION, PHOSPHORYLATION
journal title
CELL DEATH AND DIFFERENTIATION
Cell Death Differ.
volume
20
issue
7
pages
888 - 897
Web of Science type
Article
Web of Science id
000320100000009
JCR category
BIOCHEMISTRY & MOLECULAR BIOLOGY
JCR impact factor
8.385 (2013)
JCR rank
25/291 (2013)
JCR quartile
1 (2013)
ISSN
1350-9047
DOI
10.1038/cdd.2013.12
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
4101482
handle
http://hdl.handle.net/1854/LU-4101482
date created
2013-07-16 15:01:33
date last changed
2016-12-19 15:43:50
@article{4101482,
  abstract     = {There is growing evidence that the p53 tumour suppressor downregulates vascular endothelial growth factor (VEGF) expression, although the underlying mechanisms remain unclear and controversial. Here we provide insights from in vitro experiments and in vivo xenotransplantation assays that highlight a dual role for p53 in regulating VEGF during hypoxia. Unexpectedly, and for the first time, we demonstrate that p53 rapidly induces VEGF transcription upon hypoxia exposure by binding, in an HIF-1 alpha-dependent manner, to a highly conserved and functional p53-binding site within the VEGF promoter. However, during sustained hypoxia, p53 indirectly downregulates VEGF expression via the retinoblastoma (Rb) pathway in a p21-dependent manner, which is distinct from its role in cell-cycle regulation. Our findings have important implications for cancer therapy, especially for tumours that harbour wild-type TP53 and a dysfunctional Rb pathway.},
  author       = {Farhang Ghahremani, Morvarid and Goossens, Steven and Nittner, D and Bisteau, X and Bartunkova, Sona and Zwolinska, A and Hulpiau, Paco and Haigh, Katharina and Haenebalcke, Lieven and Drogat, Benjamin and Jochemsen, A and Roger, PP and Marine, Jean-Christophe and Haigh, Jody},
  issn         = {1350-9047},
  journal      = {CELL DEATH AND DIFFERENTIATION},
  keyword      = {angiogenesis,p21,p53,VEGF,HYPOXIA-INDUCIBLE FACTOR,GROWTH-FACTOR GENE,WILD-TYPE P53,FACTOR-BINDING SITES,TUMOR ANGIOGENESIS,FACTOR 1-ALPHA,CELL-CYCLE,RETINOBLASTOMA,TRANSCRIPTION,PHOSPHORYLATION},
  language     = {eng},
  number       = {7},
  pages        = {888--897},
  title        = {p53 promotes VEGF expression and angiogenesis in the absence of an intact p21-Rb pathway},
  url          = {http://dx.doi.org/10.1038/cdd.2013.12},
  volume       = {20},
  year         = {2013},
}

Chicago
Farhang Ghahremani, Morvarid, Steven Goossens, D Nittner, X Bisteau, Sona Bartunkova, A Zwolinska, Paco Hulpiau, et al. 2013. “P53 Promotes VEGF Expression and Angiogenesis in the Absence of an Intact p21-Rb Pathway.” Cell Death and Differentiation 20 (7): 888–897.
APA
Farhang Ghahremani, M., Goossens, S., Nittner, D., Bisteau, X., Bartunkova, S., Zwolinska, A., Hulpiau, P., et al. (2013). p53 promotes VEGF expression and angiogenesis in the absence of an intact p21-Rb pathway. CELL DEATH AND DIFFERENTIATION, 20(7), 888–897.
Vancouver
1.
Farhang Ghahremani M, Goossens S, Nittner D, Bisteau X, Bartunkova S, Zwolinska A, et al. p53 promotes VEGF expression and angiogenesis in the absence of an intact p21-Rb pathway. CELL DEATH AND DIFFERENTIATION. 2013;20(7):888–97.
MLA
Farhang Ghahremani, Morvarid, Steven Goossens, D Nittner, et al. “P53 Promotes VEGF Expression and Angiogenesis in the Absence of an Intact p21-Rb Pathway.” CELL DEATH AND DIFFERENTIATION 20.7 (2013): 888–897. Print.