Differential signaling through NFκB does not ameliorate skeletal myoblast apoptosis during differentiation

Abstract

During 23A2 skeletal myoblast differentiation, roughly 30% of the population undergoes apoptosis. Further, constitutive signaling by G12V:H‐Ras or Raf:CAAX abrogates this apoptosis. In this study, we demonstrate an increase in NFκB activity in myoblasts that have survived and are expressing muscle‐specific genes. NFκB activity is also elevated in myoblasts expressing constitutively active G12V:H‐Ras but not Raf:CAAX. Expression of a dominant negative IκB (IκB‐SR) sufficient to eliminate this elevated level of NFκB activity, in either the 23A2 myoblasts or their G12V:H‐Ras‐expressing counterparts, however, does not affect survival. Furthermore, expression of a constitutively active IκB kinase in 23A2 myoblasts does not protect these cells from the apoptosis associated with differentiation. Since signaling by IκB kinase can abrogate differentiation, this result demonstrates that abrogated differentiation and abrogated apoptosis are separable phenotypes.