PXD043816-2

PXD043816 is an original dataset announced via ProteomeXchange.

Title	Increased activity of protein kinase A, even without DNAJB1, is sufficient to cause Fibrolamellar hepatocellular carcinoma
Description	Most fibrolamellar carcinoma (FLC) is driven by a fusion of DNAJB1 and PRKACA, the catalytic subunit of protein kinase A (PKA). PKA holoenzyme activity is controlled through a regulatory protein (R) that both inhibits and localizes catalytic activity. An excess of regulatory subunits ensures PRKACA activity is normally inhibited. In FLC patient tumors driven by DNAJB1::PRKACA we find an increase in the ratio of catalytic to regulatory units by mass spectrometry, biochemistry and immunofluorescence, with increased kinase in the nucleus. Overexpression of DNAJB1::PRKACA, ATP1B1::PRKACA or PRKACA, but not catalytically inactive kinase, caused similar transcriptomic changes of primary human hepatocytes; these recapitulated most changes observed in FLC. This is consistent with the observation that FLC is found in patients missing a regulatory subunit or with a ATP1B1::PRKACA fusion. Thus, the DNAJB1 domain is not required for FLC. Instead, changes in PKA quantity and localization determine the FLC phenotype.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:39:35.224.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Soren Heissel
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue
Instrument	Q Exactive HF; Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-16 09:07:43	ID requested
1	2024-05-16 18:39:56	announced
⏵ 2	2024-10-22 06:39:35	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Liver cancer, Tumorigenesis, Fusion oncoprotein, Childhood cancer, Adolescent and young adult cancer, Protein kinase A, Fibrolamellar carcinoma

Sanford M. Simon
contact affiliation	Laboratory of Cellular Biophysics, The Rockefeller University, 1230 York Avenue, New York, NY 10065 USA
contact email	simon@rockefeller.edu
lab head
Soren Heissel
contact affiliation	Research Support Specialist
contact email	sheissel@rockefeller.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD043816
     1. Label: PRIDE project
     2. Name: Increased activity of protein kinase A, even without DNAJB1, is sufficient to cause Fibrolamellar hepatocellular carcinoma