Open AccessiASPP, a previously unidentified regulator of desmosomes, prevents arrhythmogenic right ventricular cardiomyopathy (ARVC)-induced sudden death
Author(s) -
Mario Notari,
Ying Hu,
Gopinath Sutendra,
Zinaida Dedeić,
Min Lü,
Laurent Dupays,
Arash Yavari,
Carolyn A. Carr,
Shan Zhong,
Aaisha Opel,
Andrew Tinker,
Kieran Clarke,
Hugh Watkins,
David Ferguson,
David P. Kelsell,
Sofia de Noronha,
Mary N. Sheppard,
Mike Hollinshead,
Timothy J. Mohun,
Xin Lü
Publication year - 2015
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1408111112
Subject(s) - desmoplakin , desmosome , sudden death , regulator , microbiology and biotechnology , desmin , cardiomyopathy , programmed cell death , biology , heart failure , medicine , cardiology , cancer research , apoptosis , cell , genetics , gene , vimentin , immunohistochemistry
Significance Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disease that is selective to the right side of the heart and results in heart failure and sudden death. Genetic defects in desmosome components account for approximately 50% of human ARVC cases; in the other 50% of patients, however, the causes remain unknown. We show that inhibitor of apoptosis-stimulating protein of p53 (iASPP) is an important regulator of desmosomes. It interacts with desmoplakin and desmin in cardiomyocytes and regulates desmosome integrity and intermediate filaments. iASPP-deficient mice display pathological features of ARVC and die of sudden death. In human ARVC patients, cardiomyocytes exhibit reduced levels of iASPP at the cell junctions, suggesting that iASPP may be critical in ARVC pathogenesis.
Accelerating Research
Robert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom
Address
John Eccles HouseRobert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom