PXD003795

PXD003795 is an original dataset announced via ProteomeXchange.

Title	Protein kinase A-dependent phosphorylation stimulates the transcriptional activity of hypoxia-inducible factor 1, part 2
Description	Hypoxia-inducible factor 1 (HIF-1) activates the transcription of genes encoding proteins that enable cells to adapt to reduced O2 availability. HIF-1 controls physiological processes that are dysregulated in cancer and heart disease, including angiogenesis, energy metabolism, and immunity. These disease processes are also characterized by increased activation of adenosine and β-adrenergic receptors, which triggers the synthesis of cyclic adenosine monophosphate (cAMP), the allosteric regulator of cAMP-dependent protein kinase A (PKA). We performed a proteomic screen in cardiomyocytes and identified PKA as a HIF-1α-interacting protein. PKA interacted with HIF-1α and phosphorylated Thr63 and Ser692 in vitro, coimmunoprecipitated with HIF-1α from cell lysates, and enhanced HIF transcriptional activity and target gene expression in human HeLa cells and rat cardiomyocytes. PKA inhibited the proteasomal degradation of HIF-1α in an O2-independent manner that required phosphorylation of Thr63 and Ser692 and was not affected by mutation of Pro402 and Pro564. PKA also stimulated the binding of the coactivator p300 to HIF- 1α to enhance its transcriptional activity and this effect was lost upon mutation of Asn803. These data establish a potential link between stimuli that increase cAMP concentrations and HIF-1α-dependent changes in gene expression, which contribute to the pathophysiology of cancer and heart disease.
HostingRepository	PRIDE
AnnounceDate	2016-06-07
AnnouncementXML	Submission_2016-06-07_04:04:34.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Vidya Venkatraman
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue; phosphorylated residue; carbamoylated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2016-03-16 03:41:36	ID requested
⏵ 1	2016-06-07 04:04:36	announced

Bullen JW, Tchernyshyov I, Holewinski RJ, DeVine L, Wu F, Venkatraman V, Kass DL, Cole RN, Van Eyk J, Semenza GL, Protein kinase A-dependent phosphorylation stimulates the transcriptional activity of hypoxia-inducible factor 1. Sci Signal, 9(430):ra56(2016) [pubmed]

submitter keyword: HIF, PKA, hypoxia, cardiomyocyte, cancer cell, cAMP, phosphorylation

Gregg L. Semenza
contact affiliation	Vascular Program, Institute for Cell Engineering Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
contact email	gsemenza@jhmi.edu
lab head
Vidya Venkatraman
contact affiliation	Cedars-Sinai Medical Center
contact email	vidya.venkatraman@cshs.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD003795
     1. Label: PRIDE project
     2. Name: Protein kinase A-dependent phosphorylation stimulates the transcriptional activity of hypoxia-inducible factor 1, part 2