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- Title
The hypoxia-inducible factor-1 DNA recognition site is cAMP-responsive.
- Authors
Wenger, Roland H.; Kvietikova, Ivica; Gassmann, Max; Marti, Hugo H.
- Abstract
The hypoxia-inducible factor-1 (HIF-1) was first described as a DNA binding activity that S<em>p</em>ecifically recognizes an 8 bp hypoxia reS<em>p</em>onse 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 atmoS<em>p</em>here. In addition to HIF-1, a constitutive DNA binding activity also S<em>p</em>ecifically binds the HIF-1 probe. Based on EMSAs using competitor oligonucleotides, S<em>p</em>ecific 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 reS<em>p</em>onsive 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 S<em>p</em>-cAMPS and the PKA inhibitor R<em>p</em>-cAMPS: while S<em>p</em>-cAMPS was synergistic with hypoxia on the HIF-1 DNA recognition site, the R<em>p</em>-cAMPS isomer showed no effect. Our findings suggest that the PKA-signaling pathway is enhancing oxygen-dependent gene expression via the HRE.
- Publication
Kidney International, 1997, Vol 51, Issue 2, p564
- ISSN
0085-2538
- Publication type
Academic Journal
- DOI
10.1038/ki.1997.79