| Autor: |
Boudreau É; Interdisciplinary School of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada., Labib S, Bertrand AT, Decostre V, Bolongo PM, Sylvius N, Bonne G, Tesson F |
| Jazyk: |
angličtina |
| Zdroj: |
PloS one [PLoS One] 2012; Vol. 7 (9), pp. e45918. Date of Electronic Publication: 2012 Sep 21. |
| DOI: |
10.1371/journal.pone.0045918 |
| Abstrakt: |
A-type lamins A and C are nuclear intermediate filament proteins in which mutations have been implicated in multiple disease phenotypes commonly known as laminopathies. A few studies have implicated sumoylation in the regulation of A-type lamins. Sumoylation is a post-translational protein modification that regulates a wide range of cellular processes through the attachment of small ubiquitin-related modifier (sumo) to various substrates. Here we showed that laminopathy mutants result in the mislocalization of sumo1 both in vitro (C2C12 cells overexpressing mutant lamins A and C) and in vivo (primary myoblasts and myopathic muscle tissue from the Lmna(H222P/H222P) mouse model). In C2C12 cells, we showed that the trapping of sumo1 in p.Asp192Gly, p.Gln353Lys, and p.Arg386Lys aggregates of lamin A/C correlated with an increased steady-state level of sumoylation. However, lamin A and C did not appear to be modified by sumo1. Our results suggest that mutant lamin A/C alters the dynamics of sumo1 and thus misregulation of sumoylation may be contributing to disease progression in laminopathies. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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