The hypoxia-inducible factor-1 DNA recognition site is cAMP-responsive.

Abstract:

: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.

journal_name

Kidney Int

journal_title

Kidney international

authors

Kvietikova I,Wenger RH,Marti HH,Gassmann M

doi

10.1038/ki.1997.80

subject

Has Abstract

pub_date

1997-02-01 00:00:00

pages

564-6

issue

2

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(15)59920-1

journal_volume

51

pub_type

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