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PXD041228

PXD041228 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePRM data for "Functional analysis of a common BAG3 allele associated with protection from heart failure"
DescriptionManuscript abstract: "Multiple genetic association studies have correlated a common allelic block linked to the BAG3 gene with a decreased incidence of heart failure, but the molecular mechanism for such protection remains elusive. One of the variants in this allele block is coding, changing cysteine to arginine at position 151 of BAG3 (rs2234962-BAG3C151R). Here, we use induced pluripotent stem cells (iPSC) to test if the BAG3C151R variant alters protein and cellular function in human cardiac myocytes. Quantitative protein interaction network analysis identified specific changes in BAG3C151R protein interaction partners in cardiomyocytes but not in iPSCs or an immortalized cell line. Knockdown of BAG3 interacting factors in cardiomyocytes followed by myofibrillar analysis revealed that BAG3C151R associates more strongly with proteins involved in the maintenance of myofibrillar integrity. Finally, we demonstrate that cardiomyocytes expressing the BAG3C151R variant have improved response to proteotoxic stress in an allele dose-dependent manner. This study suggests that the BAG3C151R variant increases cardiomyocyte protection from stress by enhancing the recruitment of factors critical to the maintenance of myofibril integrity, hinting that this variant could be responsible for the cardioprotective effect of the haplotype block. By revealing specific changes in preferential binding partners of the BAG3C151R protein variant, we also identify potential targets for the development of novel cardioprotective therapies."
HostingRepositoryPanoramaPublic
AnnounceDate2023-05-22
AnnouncementXMLSubmission_2023-05-22_20:11:19.662.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportsupported by repository but incomplete data and/or metadata
PrimarySubmitterJuan Perez-Bermejo
SpeciesList scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationListAcetyl; Phospho; Carbamidomethyl
InstrumentQ Exactive Plus
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-03-30 18:23:39ID requested
12023-05-22 20:11:20announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: iPS-CM cardiomyocytes PRM BAG3
Contact List
Ruth Huttenhain
contact affiliationUniversity of California San Francisco
contact emailruth.huttenhain@ucsf.edu
lab head
Juan Perez-Bermejo
contact affiliationGladstone Institutes
contact emailjuan.perezbermejo@gladstone.ucsf.edu
dataset submitter
Full Dataset Link List
Panorama Public dataset URI