Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
J Biol Chem ; 284(39): 26964-77, 2009 Sep 25.
Article in English | MEDLINE | ID: mdl-19643733

ABSTRACT

The fhl1 gene encoding four-and-a-half LIM protein-1 (FHL1) and its spliced isoform, SLIMMER, is mutated in reducing body myopathy, X-linked myopathy with postural muscle atrophy, scapuloperoneal myopathy, and rigid spine syndrome. In this study we have identified a novel function for SLIMMER in delaying skeletal muscle apoptosis via an interaction with the proapoptotic protein Siva-1. Siva-1 was identified as a SLIMMER-specific-interacting protein using yeast two-hybrid screening, direct-binding studies, and glutathione S-transferase pulldown analysis of murine skeletal muscle lysates. In C2C12 skeletal myoblasts, SLIMMER and Siva co-localized in the nucleus; however, both proteins exhibited redistribution to the cytoplasm following the differentiation of mononucleated myoblasts to multinucleated myotubes. In sections of mature skeletal muscle from wild type mice, SLIMMER and Siva-1 co-localized at the Z-line. SLIMMER and Siva-1 were also enriched in Pax-7-positive satellite cells, muscle stem cells that facilitate repair and regeneration. Significantly, SLIMMER delayed Siva-1-dependent apoptosis in C2C12 myoblasts. In skeletal muscle sections from the mdx mouse model of Duchenne muscular dystrophy, SLIMMER and Siva-1 co-localized in the nucleus of apoptotic myofibers. Therefore, SLIMMER may protect skeletal muscle from apoptosis.


Subject(s)
Apoptosis , Intracellular Signaling Peptides and Proteins/metabolism , Muscle Proteins/metabolism , Myoblasts, Skeletal/metabolism , Animals , Apoptosis Regulatory Proteins , Binding Sites , Blotting, Western , COS Cells , Cell Line , Cell Nucleus/metabolism , Chlorocebus aethiops , Female , Flow Cytometry , Intracellular Signaling Peptides and Proteins/genetics , LIM Domain Proteins , Male , Mice , Mice, Inbred C57BL , Mice, Inbred mdx , Microscopy, Confocal , Muscle Fibers, Skeletal/metabolism , Muscle Proteins/genetics , Muscular Dystrophy, Duchenne/metabolism , Muscular Dystrophy, Duchenne/pathology , Mutation , Myoblasts, Skeletal/cytology , Protein Binding , Protein Isoforms/genetics , Protein Isoforms/metabolism , Time Factors , Two-Hybrid System Techniques
SELECTION OF CITATIONS
SEARCH DETAIL
...