necdin enhances myoblasts survival by facilitating the degradation of the mediator of apoptosis ccar1carp1necdin提高成肌细胞生存通过促进凋亡ccar1carp1中介的退化.pdfVIP

Necdin Enhances Myoblasts Survival by Facilitating the Degradation of the Mediator of Apoptosis CCAR1/CARP1 1 1 1 2 1 Stephanie Franc¸ois , Cristina D’Orlando , Tiziana Fatone , Thierry Touvier , Patrizia Pessina , Raffaella Meneveri1, Silvia Brunelli1,3* 1 Department of Experimental Medicine, University of Milano-Bicocca, Monza, Italy, 2 E. Medea Scientific Institute, Bosisio Parini, Lecco, Italy, 3 Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy Abstract 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. Citation: Franc¸ois S, D’Orlando C, Fatone T, Touvier T, Pessina P, et al. (2012) Necdin Enhances Myoblasts Survival by Facilitating the Degradation of the Mediator of Apop