TY - JOUR
T1 - The involvement of proteasome in myogenic differentiation of murine myocytes and human rhabdomyosarcoma cells
AU - Mugita, Norifumi
AU - Honda, Yoshiomi
AU - Nakamura, Hideo
AU - Fujiwara, Toshiyoshi
AU - Tanaka, Keiji
AU - Omura, Satoshi
AU - Shimbara, Naoki
AU - Ogawa, Michio
AU - Saya, Hideyuki
AU - Nakao, Mitsuyoshi
PY - 1999
Y1 - 1999
N2 - The murine C2C12 myocytes terminally differentiate to myotubes in the mitogen-depletion, and a portion of the cells undergo apoptosis. In this study, a specific proteasome inhibitor lactacystin induced cell cycle withdrawal and precocious expression of myosin in C2C12 cells in mitogen-enriched medium, but these cells did not fuse to form myotubes. Mitogen-starved myocytes could not differentiate to myotubes under the proteasome inhibition. The genes for p21, MyoD, Myogenin and RB were activated, and p27 gene was repressed under the proteasome inhibition, suggesting the transcriptional regulation of these genes linked to the proteasome activity. The induction of p21 prior to MyoD may contribute to the incomplete myogenesis in the presence of lactacystin. In addition, lactacystin-treated C2C12 cells did not undergo apoptosis, while proteasome accumulated in the nuclei of apoptotic cells but not in those of myotubes during mitogen-depleted differentiation. Further, lactacystin induced similarly incomplete differentiation in human RD embryonal rhabdomyosarcoma cells. Our findings demonstrated that proteasome has an essential role in myogenesis, especially in transcriptional control of myogenic and cell cycle regulators, cell fusion forming myotubes, and apoptosis.
AB - The murine C2C12 myocytes terminally differentiate to myotubes in the mitogen-depletion, and a portion of the cells undergo apoptosis. In this study, a specific proteasome inhibitor lactacystin induced cell cycle withdrawal and precocious expression of myosin in C2C12 cells in mitogen-enriched medium, but these cells did not fuse to form myotubes. Mitogen-starved myocytes could not differentiate to myotubes under the proteasome inhibition. The genes for p21, MyoD, Myogenin and RB were activated, and p27 gene was repressed under the proteasome inhibition, suggesting the transcriptional regulation of these genes linked to the proteasome activity. The induction of p21 prior to MyoD may contribute to the incomplete myogenesis in the presence of lactacystin. In addition, lactacystin-treated C2C12 cells did not undergo apoptosis, while proteasome accumulated in the nuclei of apoptotic cells but not in those of myotubes during mitogen-depleted differentiation. Further, lactacystin induced similarly incomplete differentiation in human RD embryonal rhabdomyosarcoma cells. Our findings demonstrated that proteasome has an essential role in myogenesis, especially in transcriptional control of myogenic and cell cycle regulators, cell fusion forming myotubes, and apoptosis.
KW - Apoptosis
KW - Lactacystin
KW - Myogenesis
KW - Proteasome
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U2 - 10.3892/ijmm.3.2.127
DO - 10.3892/ijmm.3.2.127
M3 - Article
C2 - 9917519
AN - SCOPUS:0033068608
SN - 1107-3756
VL - 3
SP - 127
EP - 137
JO - International journal of molecular medicine
JF - International journal of molecular medicine
IS - 2
ER -