PMID- 9027740
OWN - NLM
STAT- MEDLINE
DCOM- 19970519
LR  - 20220309
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 51
IP  - 2
DP  - 1997 Feb
TI  - The hypoxia-inducible factor-1 DNA recognition site is cAMP-responsive.
PG  - 564-6
AB  - The hypoxia-inducible factor-1 (HIF-1) was first described as a DNA binding 
      activity that specifically recognizes an 8 bp hypoxia response element (HRE) 
      known to be essential for oxygen-regulated erythropoietin gene expression. In 
      electrophoretic mobility shift assays (EMSAs) HIF-1 DNA binding activity is only 
      detectable in nuclear extracts of cells cultivated in a low oxygen atmosphere. In 
      addition to HIF-1, a constitutive DNA binding activity also specifically binds 
      the HIF-1 probe. Based on EMSAs using competitor oligonucleotides, specific 
      antibodies and recombinant proteins, we previously reported that the constitutive 
      HRE binding factor is composed of ATF-1 and CREB-1. Here we show that this site 
      is functionally responsive to the cAMP agonist 8Br-cAMP in a dose-dependent 
      manner under hypoxic but not under normoxic conditions. These results were 
      confirmed by using the protein kinase A (PKA) activator Sp-cAMPS and the PKA 
      inhibitor Rp-cAMPS: while Sp-cAMPS was synergistic with hypoxia on the HIF-1 DNA 
      recognition site, the Rp-cAMPS isomer showed no effect. Our findings suggest that 
      the PKA-signaling pathway is enhancing oxygen-dependent gene expression via the 
      HRE.
FAU - Kvietikova, I
AU  - Kvietikova I
AD  - Institute of Physiology, University of Zurich-Irchel, Switzerland.
FAU - Wenger, R H
AU  - Wenger RH
FAU - Marti, H H
AU  - Marti HH
FAU - Gassmann, M
AU  - Gassmann M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Transcription Factors)
RN  - 11096-26-7 (Erythropoietin)
RN  - 23583-48-4 (8-Bromo Cyclic Adenosine Monophosphate)
RN  - 9007-49-2 (DNA)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
SB  - IM
MH  - 8-Bromo Cyclic Adenosine Monophosphate/pharmacology
MH  - Binding Sites
MH  - Cell Hypoxia/genetics/physiology
MH  - Cyclic AMP/*metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors/metabolism
MH  - DNA/genetics/*metabolism
MH  - DNA-Binding Proteins/*metabolism
MH  - Enzyme Activation/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Erythropoietin/genetics
MH  - Gene Expression Regulation
MH  - Genes, Reporter
MH  - HeLa Cells
MH  - Humans
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Luciferases/genetics
MH  - Nuclear Proteins/*metabolism
MH  - *Transcription Factors
MH  - Transfection
EDAT- 1997/02/01 00:00
MHDA- 1997/02/01 00:01
CRDT- 1997/02/01 00:00
PHST- 1997/02/01 00:00 [pubmed]
PHST- 1997/02/01 00:01 [medline]
PHST- 1997/02/01 00:00 [entrez]
AID - S0085-2538(15)59920-1 [pii]
AID - 10.1038/ki.1997.80 [doi]
PST - ppublish
SO  - Kidney Int. 1997 Feb;51(2):564-6. doi: 10.1038/ki.1997.80.