Molecular Basis for the Regulation of Transcriptional Coactivator p300 in Myogenic Differentiation.
Skeletal myogenesis is a highly ordered process which specifically depends on the function of transcriptional coactivator p300. Previous studies have established that Akt/protein kinase B (PKB), a positive regulator of p300 in proliferating cells, is also important for proper skeletal muscle development. Nevertheless, it is not clear as to how the p300 is regulated by myogenic signaling events given that both p300 and Akt are involved in many cellular processes. Our studies revealed that the levels of p300 protein are temporally maintained in ligand-enhanced skeletal myocyte development. Interestingly, this maintenance of p300 protein is observed at the stage of myoblast differentiation, which coincides with an increase in Akt phosphorylation. Moreover, regulation of p300 during myoblast differentiation appears to be mediated by Akt signaling. Blunting of p300 impairs myogenic expression and myoblast differentiation. Thus, our data suggests a particular role for Akt in myoblast differentiation through interaction with p300. Our studies also establish the potential of exploiting p300 regulation and Akt activation to decipher the complex signaling cascades involved in skeletal muscle development.
Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Jihong
J
Chen
Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Yingjian
Y
Wang
Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Munerah
M
Hamed
Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Natascha
N
Lacroix
Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.|Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Qiao
Q
Li
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D050881:E1A-Associated p300 Protein / Q000378:metabolism*; D004789:Enzyme Activation; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D024510:Muscle Development / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding; D055550:Protein Stability; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014212:Tretinoin / Q000494:pharmacology
D014212:Tretinoin; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D051057:Proto-Oncogene Proteins c-akt