Lamin A-C Mutants Disturb Sumo1 Localization and Sumoylation in Vitro and in VivoReportar como inadecuado

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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 LmnaH222P-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.

Autor: Émilie Boudreau, Sarah Labib, Anne T. Bertrand, Valérie Decostre, Pierrette M. Bolongo, Nicolas Sylvius, Gisèle Bonne, Frédé



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