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A more recent version of this article appeared on April 1, 2008
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Submitted on August 22, 2007
Revised on January 14, 2008
Accepted on January 25, 2008
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Isoforms in Myogenic Differentiation
*Department of Biochemistry, The Hong Kong University of Science and Technology, Clearwater Bay, Kowloon, Hong Kong, China;
Dana-Farber Cancer Institute, Boston, MA 02115;
Department of Pathophysiology, Southern Medical University, Guangzhou 510515, China
Monitoring Editor: Marianne Bronner-Fraser
We and others previously showed that p38 mitogen-activated protein kinase (MAPK) 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 p38
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are expressed with distinct expression patterns during differentiation. Knockdown of any of them by siRNA 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 compared the whole-genome gene expression profiles by microarrays. We found that some genes are coregulated by all three p38 isoforms, while 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.