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PLoS One ; 7(8): e43335, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22905258

RESUMO

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.


Assuntos
Proteínas Reguladoras de Apoptose/biossíntese , Apoptose , Proteínas de Ciclo Celular/biossíntese , Regulação da Expressão Gênica , Mioblastos/citologia , Proteínas do Tecido Nervoso/biossíntese , Proteínas Nucleares/biossíntese , Ubiquitina-Proteína Ligases/biossíntese , Animais , Diferenciação Celular , Sobrevivência Celular , Biblioteca Gênica , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Desenvolvimento Muscular , Músculos/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Células Satélites de Músculo Esquelético/citologia , Técnicas do Sistema de Duplo-Híbrido
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