PMID- 12570801
OWN - NLM
STAT- MEDLINE
DCOM- 20030417
LR  - 20190728
IS  - 1381-6128 (Print)
IS  - 1381-6128 (Linking)
VI  - 9
IP  - 7
DP  - 2003
TI  - Protein kinases and the hypoxia-inducible factor-1, two switches in angiogenesis.
PG  - 531-41
AB  - In the last few decades it has become clear that detailed understanding of the 
      mechanisms of angiogenesis, a process leading to growth of new blood vessels, 
      should lead to improved treatment of diseases such as ischemic disorders and 
      cancer where neovascularization is impaired or activated, respectively. In this 
      review, we will outline some of our recent findings concerning the regulation of 
      the vascular endothelial growth factor (VEGF), a key player in angiogenesis and 
      one of its transcription factors, the hypoxia-inducible factor-1 (HIF-1) a master 
      gene product driving adaptation to hypoxia. We will discuss the observation that 
      growth factors and oncogenic transformation via the mitogen-activated protein 
      kinases p42/p44 MAPKs not only activate the VEGF promoter through the Sp1/AP-2 
      transcriptional factor complex but also phosphorylate HIF-1alpha leading in turn 
      to enhance HIF-1 dependent transcriptional activation of VEGF. The 
      stress-activated protein kinases (SAPK) also contribute to angiogenesis by 
      stabilizing VEGF mRNA. Finally, we will present recent advances into 
      oxygen-sensing, in particular the HIF-hydroxylases that govern HIF-1alpha 
      instability (PHD2) or inactivation (FIH-1). The revelation of these oxygen 
      sensors has provided pharmacologists with new molecular targets for the 
      development of novel therapies to control angiogenesis either positively or 
      negatively.
FAU - Mazure, N M
AU  - Mazure NM
AD  - Institute of Signaling, Developmental Biology and Cancer Research, CNRS-UMR 6543, 
      Centre Antoine Lacassagne, 33 Avenue de Valombrose, 06189 Nice, France.
FAU - Brahimi-Horn, M C
AU  - Brahimi-Horn MC
FAU - Pouyssegur, J
AU  - Pouyssegur J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United Arab Emirates
TA  - Curr Pharm Des
JT  - Current pharmaceutical design
JID - 9602487
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Endothelial Growth Factors)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Lymphokines)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Vascular Endothelial Growth Factors)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Cell Hypoxia/physiology
MH  - DNA-Binding Proteins/genetics/*physiology
MH  - Endothelial Growth Factors/genetics/*physiology
MH  - Endothelium/enzymology
MH  - Gene Expression/physiology
MH  - Humans
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Intercellular Signaling Peptides and Proteins/genetics/*physiology
MH  - Lymphokines/genetics/*physiology
MH  - Mitogen-Activated Protein Kinases/*physiology
MH  - Neovascularization, Pathologic/*physiopathology
MH  - Neovascularization, Physiologic/*physiology
MH  - Nuclear Proteins/genetics/*physiology
MH  - Transcription Factors/genetics/physiology
MH  - Transcriptional Activation
MH  - Vascular Endothelial Growth Factor A
MH  - Vascular Endothelial Growth Factors
RF  - 62
EDAT- 2003/02/07 04:00
MHDA- 2003/04/18 05:00
CRDT- 2003/02/07 04:00
PHST- 2003/02/07 04:00 [pubmed]
PHST- 2003/04/18 05:00 [medline]
PHST- 2003/02/07 04:00 [entrez]
AID - 10.2174/1381612033391469 [doi]
PST - ppublish
SO  - Curr Pharm Des. 2003;9(7):531-41. doi: 10.2174/1381612033391469.