The Small Heat Shock Protein αB-crystallin Negatively Regulates Apoptosis during Myogenic Differentiation by Inhibiting Caspase-3 Activation

摘要: Myoblasts respond to growth factor deprivation either by differentiating into multinucleated myotubes or undergoing apoptosis; hence, the acquisition of apoptosis resistance myogenic precursors is essential for their development. Here we demonstrate that expression small heat shock protein alpha B-crystallin selectively induced in C2C12 myoblasts are resistant differentiation-induced apoptosis, and show this induction occurs at an early stage differentiation vitro. In contrast, several known anti-apoptotic proteins (FLIP, XIAP, Bcl-x(L)) was not altered during myogenesis. We also ectopic B-crystallin, but closely related Hsp27, renders apoptosis. Furthermore, myopathy-causing R120G mutant partly impaired its cytoprotective function, whereas a pseudophosphorylation mimics stress-induced phosphorylation completely devoid activity. Finally, negatively regulates myogenesis inhibiting proteolytic activation caspase-3, mutants defective function. Taken together, our findings indicate novel negative regulator directly links program resistance.