Research ArticleCell Biology

Protein kinase A–dependent phosphorylation stimulates the transcriptional activity of hypoxia-inducible factor 1

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Science Signaling  31 May 2016:
Vol. 9, Issue 430, pp. ra56
DOI: 10.1126/scisignal.aaf0583

Enhancing hypoxic responses with PKA

The genes targeted by the transcription factor HIF-1 are involved in adapting to low-oxygen conditions. However, responses mediated by HIF-1 also contribute to the pathogenesis of cancer and cardiovascular disease. The second messenger cAMP is increased in cancer cells and initially increased in failing hearts. Bullen et al. found that the cAMP-activated kinase PKA phosphorylated HIF-1α, which increased its abundance and activity in cultured cardiomyocytes and a cancer cell line. Stimuli that increased cAMP concentrations enhanced the expression of HIF-1 target genes encoding enzymes that convert cAMP to adenosine, a metabolite that suppresses antitumor immunity and reduces heart rate and contractility. Thus, these data establish a mechanistic link between a kinase (PKA) and transcription factor (HIF-1) that contribute to the progression of cancer and cardiovascular disease.

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