MBNL142 and MBNL143 gene isoforms, overexpressed in DM1-patient muscle, encode for nuclear proteins interacting with Src family kinases
Articolo
Data di Pubblicazione:
2013
Citazione:
MBNL142 and MBNL143 gene isoforms, overexpressed in DM1-patient muscle, encode for nuclear proteins interacting with Src family kinases / A. Botta, A. Malena, E. Tibaldi, L. Rocchi, E. Loro, E. Pena, L. Cenci, E. Ambrosi, M.C. Bellocchi, M.A. Pagano, G. Novelli, G. Rossi, H.L. Monaco, E. Gianazza, B. Pantic, V. Romeo, O. Marin, A.M. Brunati, L. Vergani. - In: CELL DEATH & DISEASE. - ISSN 2041-4889. - 4:8(2013), pp. e770.1-e770.12. [10.1038/cddis.2013.291]
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 pre-mRNAs. The longer muscleblind-like-1 (MBNL1) transcripts containing exon 5 and the respective protein isoforms (MBNL1 42-43) were found to be overexpressed in DM1 muscle and localized exclusively in the nuclei. In vitro assays showed that MBNL1 42-43 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-MBNL1 42-43, succeeded in reducing the nuclear localization of both Lyn and MBNL1 42-43 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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
MBNL1; DM1; SFKs; muscle; pre-messenger-rna; lyn tyrosine kinase; proline-rich motif; myotonic-dystrophy; SH3 domain; lipid rafts; CTG repeat; in-vivo; C-SRC; activation
Elenco autori:
A. Botta, A. Malena, E. Tibaldi, L. Rocchi, E. Loro, E. Pena, L. Cenci, E. Ambrosi, M.C. Bellocchi, M.A. Pagano, G. Novelli, G. Rossi, H.L. Monaco, E. Gianazza, B. Pantic, V. Romeo, O. Marin, A.M. Brunati, L. Vergani
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