PMID- 17916562
OWN - NLM
STAT- MEDLINE
DCOM- 20080204
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 282
IP  - 48
DP  - 2007 Nov 30
TI  - Dynamics of the hypoxia-inducible factor-1-vascular endothelial growth factor 
      promoter complex.
PG  - 35035-45
AB  - Some transactivator-promoter complexes are highly dynamic due to active 
      disruption of the complex by proteolytic or nonproteolytic mechanisms, and this 
      appears to be an important mechanism by which their activity is governed tightly 
      and eventually terminated. However, the generality of these mechanisms is 
      unclear. In this report, we address the dynamics of hypoxia-inducible factor-1 
      (HIF-1) binding to the vascular endothelial growth factor promoter. HIF-1 is a 
      heterodimeric transcription factor whose activity is triggered by an increase in 
      HIF-1alpha levels in hypoxic cells. A "competition ChIP" assay is employed to 
      demonstrate that HIF-1alpha forms a kinetically stable complex with the native 
      vascular endothelial growth factor promoter that has a half-life in excess of 1 
      h. Thus, HIF-1 activity does not require rapid proteolytic turnover of the 
      promoter-bound transactivator, nor is the activator-promoter complex constantly 
      disassembled by chaperones. However, we do find that after cessation of the 
      inducing signal, HIF-1 activity is slowly returned to basal levels by 
      proteasome-mediated proteolysis of the promoter-bound HIF-1alpha protein.
FAU - Yu, Peng
AU  - Yu P
AD  - Division of Translational Research, Department of Internal Medicine, University 
      of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9185, USA.
FAU - Kodadek, Thomas
AU  - Kodadek T
LA  - eng
GR  - GM66380/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20071003
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 9007-49-2 (DNA)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Animals
MH  - COS Cells
MH  - Chlorocebus aethiops
MH  - DNA/chemistry
MH  - Dimerization
MH  - HeLa Cells
MH  - Humans
MH  - Hypoxia
MH  - Hypoxia-Inducible Factor 1/*genetics/metabolism
MH  - Kinetics
MH  - Models, Genetic
MH  - *Promoter Regions, Genetic
MH  - Proteasome Endopeptidase Complex/metabolism
MH  - Time Factors
MH  - Vascular Endothelial Growth Factor A/*genetics/metabolism
EDAT- 2007/10/06 09:00
MHDA- 2008/02/05 09:00
CRDT- 2007/10/06 09:00
PHST- 2007/10/06 09:00 [pubmed]
PHST- 2008/02/05 09:00 [medline]
PHST- 2007/10/06 09:00 [entrez]
AID - S0021-9258(20)54641-3 [pii]
AID - 10.1074/jbc.M707557200 [doi]
PST - ppublish
SO  - J Biol Chem. 2007 Nov 30;282(48):35035-45. doi: 10.1074/jbc.M707557200. Epub 2007 
      Oct 3.