PXD020605
PXD020605 is an original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2020-07-28 04:59:26 | ID requested | |
⏵ 1 | 2023-11-18 01:37:18 | announced |
Publication List
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] |
Keyword List
submitter keyword: proteomics, Pkp2, desmosomal protein degradation,arrhythmogenic cardiomyopahty |
Contact List
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 |
Full Dataset Link List
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PRIDE project URI |
Repository Record List
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