PXD003792

PXD003792 is an original dataset announced via ProteomeXchange.

Title	Protein kinase A-dependent phosphorylation stimulates the transcriptional activity of hypoxia-inducible factor 1, part 1
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 target genes play a central role in mediating 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, co-immunoprecipitated 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	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:05:30.045.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Robert Cole
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2016-03-15 08:34:52	ID requested
1	2016-06-06 04:44:09	announced
⏵ 2	2024-10-22 04:05:38	announced	2024-10-22: Updated project metadata.

10.1126/scisignal.aaf0583;

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]

curator keyword: Biological, Biomedical

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

Gregg L Semenza
contact affiliation	Vascular Program, Institute for Cell Engineering, McKusick-Nathans Institute for Genetic Medicine, and Departments of Medicine, Biological Chemistry, Oncology, Pediatrics, and Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
contact email	gsemenza@jhmi.edu
lab head
Robert Cole
contact affiliation	Johns Hopkins University
contact email	rcole@jhmi.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2016/06/PXD003792

PRIDE project URI

• PRIDE
  1. PXD003792
     1. Label: PRIDE project
     2. Name: Protein kinase A-dependent phosphorylation stimulates the transcriptional activity of hypoxia-inducible factor 1, part 1