Involvement of the p38 mitogen-activated protein kinase alpha, beta, and gamma isoforms in myogenic differentiation.
We and others previously showed that p38 mitogen-activated protein kinase is indispensable for myogenic differentiation. However, it is less clear which of the four p38 isoforms in the mouse genome participates in this process. Using C2C12 myogenic cells as a model, we showed here that p38alpha, beta, and gamma are expressed with distinct expression patterns during differentiation. Knockdown of any of them by small interfering RNA inhibits myogenic differentiation, which suggests that the functions of the three p38 isoforms are not completely redundant. To further elucidate the unique role of each p38 isoform in myogenic differentiation, we individually knocked down one p38 isoform at a time in C2C12 cells, and we compared the whole-genome gene expression profiles by microarrays. We found that some genes are coregulated by all three p38 isoforms, whereas others are uniquely regulated by one particular p38 isoform. Furthermore, several novel p38 target genes (i.e., E2F2, cyclin D3, and WISP1) are found to be required for myogenin expression, which provides a molecular basis to explain why different p38 isoforms are required for myogenic differentiation.
Wang
Haixia
H
Department of Biochemistry, The Hong Kong University of Science and Technology, Clearwater Bay, Kowloon, Hong Kong, China.
Xu
Qing
Q
Xiao
Fang
F
Jiang
Yong
Y
Wu
Zhenguo
Z
D000818:Animals; D001483:Base Sequence; D055511:CCN Intercellular Signaling Proteins; D002454:Cell Differentiation; D002460:Cell Line; D056743:Cyclin D3; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D050703:E2F2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D051379:Mice; D048290:Mitogen-Activated Protein Kinase 11 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D048291:Mitogen-Activated Protein Kinase 12 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D024510:Muscle Development / Q000235:genetics / Q000502:physiology*; D009132:Muscles / Q000201:enzymology; D032446:Myoblasts / Q000166:cytology / Q000201:enzymology; D020411:Oligonucleotide Array Sequence Analysis; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics
D055511:CCN Intercellular Signaling Proteins; C492067:CCN4 protein, mouse; C534697:Ccnd3 protein, mouse; D056743:Cyclin D3; D016213:Cyclins; D050703:E2F2 Transcription Factor; C484940:E2f2 protein, mouse; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D048291:Mitogen-Activated Protein Kinase 12; D048290:Mitogen-Activated Protein Kinase 11; D048308:Mitogen-Activated Protein Kinase 14