Opposite roles of MRF4 and MyoD in cell proliferation and myogenic differentiation

Xun Jin, Jong Gun Kim, Myung Joo Oh, Ho Yeon Oh, Young Woo Sohn, Xumin Pian, Jin Long Yin, Samuel Beck, Namkyung Lee, Jeesoo Son, Hyunggee Kim, Changguo Yan, Ji Hui Wang, Yun Jaie Choi, Kwang Youn Whang

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The basic helix-loop-helix myogenic regulatory factors play critical roles in skeletal myogenesis. Among the myogenic regulatory factors (MRFs), MRF4 shows a biphasic expression pattern during the formation of myotomes, although its function remains unclear. In this study, we used BEF (spontaneously immortalized bovine embryonic fibroblast that shows myogenic differentiation by overexpression of MyoD) and C2C12 cells to investigate the function of MRF4. Ectopic expressions of MRF4 did not stimulate myogenic differentiation in the BEF and C2C12 cells, but did show a marked increase of cell proliferation, upregulation of cyclin E, and downregulation of p21WAF1. Furthermore, MRF4 was found to induce degradation of the MyoD protein, which acts as a transcriptional activator for p21WAF1, and thus indicates that MRF4 accelerates cell proliferation by suppressing MyoD-dependent p21WAF1 expression. However, forced expression of MyoD in the MRF4-overexpressing cells inhibited cell proliferation and partially induced myogenic differentiation, which suggests that MyoD is a potential negative intercessor of MRF4 in the regulation of the cell cycle. Taken together, these results indicate that MRF4 and MyoD play competitive roles in myogenesis by stimulating cell proliferation and differentiation, respectively.

Original languageEnglish
Pages (from-to)476-482
Number of pages7
JournalBiochemical and biophysical research communications
Volume364
Issue number3
DOIs
Publication statusPublished - 2007 Dec 21

Keywords

  • Cyclin E
  • MRF4
  • MyoD
  • Myogenic differentiation
  • Proliferation
  • p21

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Jin, X., Kim, J. G., Oh, M. J., Oh, H. Y., Sohn, Y. W., Pian, X., Yin, J. L., Beck, S., Lee, N., Son, J., Kim, H., Yan, C., Wang, J. H., Choi, Y. J., & Whang, K. Y. (2007). Opposite roles of MRF4 and MyoD in cell proliferation and myogenic differentiation. Biochemical and biophysical research communications, 364(3), 476-482. https://doi.org/10.1016/j.bbrc.2007.10.042