Increased expression of the pro-apoptotic Bcl2 family member PUMA and apoptosis by the muscle regulatory transcription factor MyoD in response to a variety of stimuli.
We have previously reported that the level of MyoD expression correlates with the level of apoptosis that occurs in a subpopulation of skeletal myoblasts induced to differentiate by serum withdrawal. Herein we document that MyoD expression contributes to the level of apoptosis in myoblasts and fibroblasts in response to a variety of apoptotic stimuli. Specifically, re-expression of MyoD in skeletal myoblasts rendered defective for both differentiation and apoptosis by the expression of oncogenic Ras restores their ability to undergo both differentiation and apoptosis in response to serum withdrawal. Further, using a fibroblast cell line expressing an estrogen receptor:MyoD fusion protein, we have determined that addition of estrogen sensitizes these fibroblasts to apoptosis induced by serum withdrawal, or by treatment with etoposide or thapsigargin. RNAi mediated silencing of MyoD in either 23A2 or C2C12 myoblasts renders these cells resistant to apoptosis induced by serum withdrawal, or by treatment with etoposide or thapsigargin. Finally, MyoD mediated regulation of the apoptotic response to these various stimuli, in both myoblasts and fibroblasts, correlates with the level of induction of the pro-apoptotic Bcl2 family member PUMA.
Harford
Terri J
TJ
Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Center for Gene Regulation in Health and Disease, Cleveland, OH 44115, USA.
Shaltouki
Atossa
A
Weyman
Crystal M
CM
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D004967:Estrogens / Q000378:metabolism*; D005047:Etoposide / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D051379:Mice; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism*; D032448:Myoblasts, Skeletal / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D004967:Estrogens; D017570:MyoD Protein; C488588:PUMA protein, mouse; D025521:Tumor Suppressor Proteins; D019284:Thapsigargin; D005047:Etoposide