Hypoxia and the hypoxia inducible factor 1α activate protein kinase A by repressing RII beta subunit transcription.

ABSTRACT: Overactivation of the cAMP signal transduction pathway plays a central role in the pathogenesis of endocrine tumors. Genetic aberrations leading to increased intracellular cAMP or directly affecting PKA subunit expression have been identified in inherited and sporadic endocrine tumors, but are rare indicating the presence of nongenomic pathological PKA activation. In the present study, we examined the impact of hypoxia on PKA activation using human growth hormone (GH)-secreting pituitary tumors as a model of an endocrine disease displaying PKA-CREB overactivation. We show that hypoxia activates PKA and enhances CREB transcriptional activity and subsequently GH oversecretion. This is due to a previously uncharacterized ability of HIF-1α to suppress the transcription of the PKA regulatory su

SUBMITTER: Lucia K 

PROVIDER: S-EPMC7160059 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature