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Sumoylation regulates lamin A function and is lost in lamin A mutants associated with familial cardiomyopathies
Lamin A mutations cause many diseases, including cardiomyopathies and Progeria Syndrome. The covalent attachment of small ubiquitin-like modifier (SUMO) polypeptides regulates the function of many proteins. Until now, no examples of human disease-causing mutations that occur within a sumoylation con...
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2008
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2447889/ https://www.ncbi.nlm.nih.gov/pubmed/18606848 http://dx.doi.org/10.1083/jcb.200712124 |
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author | Zhang, Yu-Qian Sarge, Kevin D. |
author_facet | Zhang, Yu-Qian Sarge, Kevin D. |
author_sort | Zhang, Yu-Qian |
collection | PubMed |
description | Lamin A mutations cause many diseases, including cardiomyopathies and Progeria Syndrome. The covalent attachment of small ubiquitin-like modifier (SUMO) polypeptides regulates the function of many proteins. Until now, no examples of human disease-causing mutations that occur within a sumoylation consensus sequence and alter sumoylation were known. We show that lamin A is sumoylated at lysine 201 and that two lamin A mutants associated with familial dilated cardiomyopathy, E203G and E203K, exhibit decreased sumoylation. E203 occupies the conserved +2 position in the sumoylation consensus ΨKXE. Lamin A mutants E203G, E203K, and K201R all exhibit a similar aberrant subcellular localization and are associated with increased cell death. Fibroblasts from an individual with the E203K lamin A mutation also exhibit decreased lamin A sumoylation and increased cell death. These results suggest that SUMO modification is important for normal lamin A function and implicate an involvement for altered sumoylation in the E203G/E203K lamin A cardiomyopathies. |
format | Text |
id | pubmed-2447889 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-24478892009-01-14 Sumoylation regulates lamin A function and is lost in lamin A mutants associated with familial cardiomyopathies Zhang, Yu-Qian Sarge, Kevin D. J Cell Biol Research Articles Lamin A mutations cause many diseases, including cardiomyopathies and Progeria Syndrome. The covalent attachment of small ubiquitin-like modifier (SUMO) polypeptides regulates the function of many proteins. Until now, no examples of human disease-causing mutations that occur within a sumoylation consensus sequence and alter sumoylation were known. We show that lamin A is sumoylated at lysine 201 and that two lamin A mutants associated with familial dilated cardiomyopathy, E203G and E203K, exhibit decreased sumoylation. E203 occupies the conserved +2 position in the sumoylation consensus ΨKXE. Lamin A mutants E203G, E203K, and K201R all exhibit a similar aberrant subcellular localization and are associated with increased cell death. Fibroblasts from an individual with the E203K lamin A mutation also exhibit decreased lamin A sumoylation and increased cell death. These results suggest that SUMO modification is important for normal lamin A function and implicate an involvement for altered sumoylation in the E203G/E203K lamin A cardiomyopathies. The Rockefeller University Press 2008-07-14 /pmc/articles/PMC2447889/ /pubmed/18606848 http://dx.doi.org/10.1083/jcb.200712124 Text en © 2008 Zhang and Sarge This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Zhang, Yu-Qian Sarge, Kevin D. Sumoylation regulates lamin A function and is lost in lamin A mutants associated with familial cardiomyopathies |
title | Sumoylation regulates lamin A function and is lost in lamin A mutants associated with familial cardiomyopathies |
title_full | Sumoylation regulates lamin A function and is lost in lamin A mutants associated with familial cardiomyopathies |
title_fullStr | Sumoylation regulates lamin A function and is lost in lamin A mutants associated with familial cardiomyopathies |
title_full_unstemmed | Sumoylation regulates lamin A function and is lost in lamin A mutants associated with familial cardiomyopathies |
title_short | Sumoylation regulates lamin A function and is lost in lamin A mutants associated with familial cardiomyopathies |
title_sort | sumoylation regulates lamin a function and is lost in lamin a mutants associated with familial cardiomyopathies |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2447889/ https://www.ncbi.nlm.nih.gov/pubmed/18606848 http://dx.doi.org/10.1083/jcb.200712124 |
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