Opposite roles of MRF4 and MyoD in cell proliferation and myogenic differentiation.
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.
Jin
Xun
X
Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
Kim
Jong-Gun
JG
Oh
Myung-Joo
MJ
Oh
Ho-Yeon
HY
Sohn
Young-Woo
YW
Pian
Xumin
X
Yin
Jin Long
JL
Beck
Samuel
S
Lee
Namkyung
N
Son
Jeesoo
J
Kim
Hyunggee
H
Yan
Changguo
C
Wang
Ji Hui
JH
Choi
Yun-Jaie
YJ
Whang
Kwang Youn
KY
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D051379:Mice; D032342:Muscle Cells / Q000166:cytology* / Q000502:physiology*; D024510:Muscle Development / Q000502:physiology*; D017570:MyoD Protein / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology* / Q000502:physiology*; D018006:Myogenic Regulatory Factors / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D018006:Myogenic Regulatory Factors; C063403:myogenic factor 6