期刊
DEVELOPMENTAL DYNAMICS
卷 237, 期 5, 页码 1424-1433出版社
WILEY-LISS
DOI: 10.1002/dvdy.21544
关键词
CMF1; LEK1; LEK proteins; Rb; myocyte differentiation
资金
- NCI NIH HHS [P30 CA68485, P30 CA068485] Funding Source: Medline
- NHLBI NIH HHS [K08 HL067049, R01 HL37675, R01 HL037675, R01 HL037675-17A2, K08 HL67049, K08 HL067049-05] Funding Source: Medline
CMF1 protein is expressed in developing striated muscle before the expression of contractile proteins, and depletion of CMF1 in myoblasts results in inability to express muscle-specific proteins. Previous studies of CMF1 identify a functional Rb-binding domain, which is conserved in the murine and human homologues. Here, we show that CMF1 binds Rb family members, while a CMF1 protein with deletion of the Rb-binding domain (Rb-del CMF1) does not. Myogenic cell lines over-expressing Rb-del CMF1 proliferate normally, but exhibit markedly impaired differentiation, including dramatically reduced contractile proteins gene expression and failure to fuse into myotubes. Furthermore, by quantitative real-time polymerase chain reaction, MyoD and Myf5 mRNA levels are comparable to wild-type, while myogenin and contractile protein mRNA levels are significantly attenuated. These data demonstrate that CMF1 regulates myocyte differentiation by interaction with Rb family members to induce expression of myogenic regulatory factors.
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