Genetic deficiency of p38alpha reveals its critical role in myoblast cell cycle exit: the p38alpha-JNK connection.
The regulation of skeletal muscle formation (myogenesis) is essential for normal development as well as in pathological conditions such as muscular dystrophies and inflammatory myopathies. Findings published over the past years have established a key role for the p38 MAP kinase signaling pathway in the control of muscle gene expression and myotube formation. However, the relative contribution of the four p38 MAP kinases (p38alpha, p38beta, p38gamma and p38delta) to this process was unknown. We have recently demonstrated that myoblasts lacking p38alpha, but not those lacking p38beta or p38delta, were unable to differentiate and form multinucleated myotubes, while p38gamma-deficient myoblasts exhibited an attenuated fusion capacity. Defective myogenesis in the absence of p38alpha was attributed to delayed cell cycle exit and continuous proliferation in differentiation-promoting conditions, caused by enhanced activation of the JNK/cJun pathway. We discuss these findings in the context of the emerging crosstalk of p38 and JNK signaling pathways in controlling cell growth and differentiation.
Perdiguero
Eusebio
E
Program on Differentiation and Cancer, Centre for Genomic Regulation, UPF/PRBB, CIBER de Enfermedades Neurodegenerativas, Barcelona, Spain.
Ruiz-Bonilla
Vanessa
V
Serrano
Antonio L
AL
Muñoz-Cánoves
Pura
P
D000818:Animals; D000831:Animals, Newborn; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002459:Cell Fusion; D002478:Cells, Cultured / Q000166:cytology; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D048290:Mitogen-Activated Protein Kinase 11 / Q000502:physiology; D048291:Mitogen-Activated Protein Kinase 12 / Q000502:physiology; D048292:Mitogen-Activated Protein Kinase 13 / Q000502:physiology; D048308:Mitogen-Activated Protein Kinase 14 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000166:cytology; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics; D032446:Myoblasts / Q000166:cytology*; D009363:Neoplasm Proteins / Q000378:metabolism; D009928:Organ Specificity; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012208:Rhabdomyosarcoma / Q000473:pathology
D018797:Cell Cycle Proteins; D009124:Muscle Proteins; D009363:Neoplasm Proteins; D048291:Mitogen-Activated Protein Kinase 12; D048292:Mitogen-Activated Protein Kinase 13; D048031:JNK Mitogen-Activated Protein Kinases; D048290:Mitogen-Activated Protein Kinase 11; D048308:Mitogen-Activated Protein Kinase 14