PXD020605-1

PXD020605 is an original dataset announced via ProteomeXchange.

Title	Desmosomal protein degradation accompanied by desmosomal and adherens junctions protein disarray as underlying causes of PKP2 driven arrhythmogenic cardiomyopathy
Description	Arrhythmogenic cardiomyopathy (ACM) is an inherited progressive cardiomyopathy. The pathophysiological events are well understood, yet the underlying molecular mechanisms remain undefined. Here, we created a novel research platform comprising of patient originated hiPSC-derived cardiomyocytes bearing a pathological PKP2 mutation (PKP2 c.2013delC/WT), a novel knock-in murine model carrying the equivalent mutation (Pkp2 c.1755delA/WT), and human explanted ACM hearts, to identify disease driving mechanisms. Pkp2 c.1755delA/WT mice displayed reduced desmosomal and adherens junctions protein levels and protein disarray of the intercalated discs in areas of active fibrotic remodeling. These findings were validated in hiPSC-derived cardiomyocytes and human explanted ACM hearts. Led by proteomics data, we demonstrated that the ubiquitin-proteasome system was responsible for the observed desmosomal protein degradation. The research platform presented here provides a strong scientific basis to identify bona fide pathological processes and will aid in the development of potential therapies for the prevention of ACM disease progression.
HostingRepository	PRIDE
AnnounceDate	2023-11-18
AnnouncementXML	Submission_2023-11-18_01:37:17.825.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD020605
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Xiaoke Yin
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-28 04:59:26	ID requested
⏵ 1	2023-11-18 01:37:18	announced

10.6019/PXD020605;

10.1126/scitranslmed.add4248;

Tsui H, van Kampen SJ, Han SJ, Meraviglia V, van Ham WB, Casini S, van der Kraak P, Vink A, Yin X, Mayr M, Bossu A, Marchal GA, Monshouwer-Kloots J, Eding J, Versteeg D, de Ruiter H, Bezstarosti K, Groeneweg J, Klaasen SJ, van Laake LW, Demmers JAA, Kops GJPL, Mummery CL, van Veen TAB, Remme CA, Bellin M, van Rooij E, Desmosomal protein degradation as an underlying cause of arrhythmogenic cardiomyopathy. Sci Transl Med, 15(688):eadd4248(2023) [pubmed]

submitter keyword: proteomics, Pkp2, desmosomal protein degradation,arrhythmogenic cardiomyopahty

Manuel Mayr
contact affiliation	King's British Heart Foundation Centre of Research Excellence, King's College London, London, UK
contact email	manuel.mayr@kcl.ac.uk
lab head
Xiaoke Yin
contact affiliation	Cardiovascular Division, King's College London
contact email	xiaoke.yin@kcl.ac.uk
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/2023/11/PXD020605

PRIDE project URI

• PRIDE
  1. PXD020605
     1. Label: PRIDE project
     2. Name: Desmosomal protein degradation accompanied by desmosomal and adherens junctions protein disarray as underlying causes of PKP2 driven arrhythmogenic cardiomyopathy