Necdin enhances myoblasts survival by facilitating the degradation of the mediator of apoptosis CCAR1/CARP1.
Regeneration of muscle fibers, lost during pathological muscle degeneration or after injuries, is sustained by the production of new myofibers by means of the satellite cells. Survival of the satellite cells is a critical requirement for efficient muscle reconstitution. Necdin, a member of the MAGE proteins family, is expressed in satellite cell-derived myogenic precursors during perinatal growth and in the adult upon activation during muscle regeneration, where it plays an important role both in myoblast differentiation and survival. We show here that necdin exerts its pro-survival activity by counteracting the action of the pro-apoptotic protein Cell Cycle Apoptosis Regulatory Protein (CCAR1/CARP1) that we have identified as a new molecular interactor of necdin by two-hybrid screening. Necdin is responsible for the maintenance of CCAR1 protein levels, by implementing its ubiquitination and degradation through the proteasome. Taken together, these data shed new light on the molecular mechanism of necdin anti-apoptotic activity in myogenesis.
Department of Experimental Medicine, University of Milano-Bicocca, Monza, Italy.
Stephanie
S
François
Cristina
C
D'Orlando
Tiziana
T
Fatone
Thierry
T
Touvier
Patrizia
P
Pessina
Raffaella
R
Meneveri
Silvia
S
Brunelli
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D002454:Cell Differentiation; D002470:Cell Survival; D005786:Gene Expression Regulation; D015723:Gene Library; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D024510:Muscle Development; D009132:Muscles / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009687:Nuclear Proteins / Q000096:biosynthesis*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis*
D051017:Apoptosis Regulatory Proteins; C477529:CCAR1 protein, human; C540324:CCAR1 protein, mouse; D018797:Cell Cycle Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C069766:necdin; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex