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- Title
MBNL1<sub>42</sub> and MBNL1<sub>43</sub> gene isoforms, overexpressed in DM1-patient muscle, encode for nuclear proteins interacting with Src family kinases.
- Authors
Botta, A.; Malena, A.; Tibaldi, E.; Rocchi, L.; Loro, E.; Pena, E.; Cenci, L.; Ambrosi, E.; Bellocchi, M.C.; Pagano, M.A.; Novelli, G.; Rossi, G.; Monaco, H.L.; Gianazza, E.; Pantic, B.; Romeo, V.; Marin, O.; Brunati, A.M.; Vergani, L.
- Abstract
Myotonic dystrophy type-1 (DM1) is the most prevalent form of muscular dystrophy in adults. This disorder is an RNA-dominant disease, caused by expansion of a CTG repeat in the DMPK gene that leads to a misregulation in the alternative splicing of premRNAs. The longer muscleblind-like-1 (MBNL1) transcripts containing exon 5 and the respective protein isoforms (MBNL142-43) were found to be overexpressed in DM1 muscle and localized exclusively in the nuclei. In vitro assays showed that MBNL142-43 bind the Src-homology 3 domain of Src family kinases (SFKs) via their proline-rich motifs, enhancing the SFK activity. Notably, this association was also confirmed in DM1 muscle and myotubes. The recovery, mediated by an siRNA target to Ex5-MBNL142-43, succeeded in reducing the nuclear localization of both Lyn and MBNL142-43 proteins and in decreasing the level of tyrosine phosphorylated proteins. Our results suggest an additional molecular mechanism in the DM1 pathogenesis, based on an altered phosphotyrosine signalling pathway.
- Publication
Cell Death & Disease, 2013, Vol 4, Issue 8, p1
- ISSN
2041-4889
- Publication type
Article
- DOI
10.1038/cddis.2013.291