期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 277, 期 41, 页码 38731-38736出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M201770200
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资金
- NCI NIH HHS [5T32-CA70085] Funding Source: Medline
- NINDS NIH HHS [NS31957] Funding Source: Medline
Myoblasts-respond to growth factor deprivation either by differentiating into multinucleated myotubes or by undergoing apoptosis; hence, the acquisition of apoptosis resistance by myogenic precursors is essential for their development. Here we demonstrate that the expression of the small heat shock protein alphaB-crystallin is selectively induced in C2C12 myoblasts that are resistant to differentiation-induced apoptosis, and we show that this induction occurs at an early stage in their differentiation in vitro. In contrast, the expression of several known anti-apoptotic proteins (FLIP, XLAP, Bcl-x(L)) was not altered during myogenesis. We also demonstrate that ectopic expression of alphaB-crystallin, but not the closely related small heat shock protein Hsp27, renders C2C12 myoblasts resistant to differentiation-induced apoptosis. Furthermore, we show that the myopathy-causing R120G alphaB-crystallin mutant is partly impaired in its cytoprotective function, whereas a pseudophosphorylation alphaB-crystallin mutant that mimics stress-induced phosphorylation is completely devoid of anti-apoptotic activity. Finally, we demonstrate that alphaB-crystallin negatively regulates apoptosis during myogenesis by inhibiting the proteolytic activation of caspase-3, whereas the R120G and pseudophosphorylation mutants are defective in this function. Taken together, our findings indicate that alphaB-crystallin is a novel negative regulator of myogenic apoptosis that directly links the differentiation program to apoptosis resistance.
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