PXD041228-1

PXD041228 is an original dataset announced via ProteomeXchange.

Title	PRM data for "Functional analysis of a common BAG3 allele associated with protection from heart failure"
Description	Manuscript 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."
HostingRepository	PanoramaPublic
AnnounceDate	2023-05-22
AnnouncementXML	Submission_2023-05-22_20:11:19.662.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	supported by repository but incomplete data and/or metadata
PrimarySubmitter	Juan Perez-Bermejo
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	Acetyl; Phospho; Carbamidomethyl
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-30 18:23:39	ID requested
⏵ 1	2023-05-22 20:11:20	announced

Dataset with its publication pending

submitter keyword: iPS-CM cardiomyocytes PRM BAG3

Ruth Huttenhain
contact affiliation	University of California San Francisco
contact email	ruth.huttenhain@ucsf.edu
lab head
Juan Perez-Bermejo
contact affiliation	Gladstone Institutes
contact email	juan.perezbermejo@gladstone.ucsf.edu
dataset submitter

Panorama Public dataset URI