The involvement of proteasome in myogenic differentiation of murine myocytes and human rhabdomyosarcoma cells

Norifumi Mugita, Yoshiomi Honda, Hideo Nakamura, Toshiyoshi Fujiwara, Keiji Tanaka, Satoshi Omura, Naoki Shimbara, Michio Ogawa, Hideyuki Saya, Mitsuyoshi Nakao

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)127-137
Number of pages11
JournalInternational journal of molecular medicine
Volume3
Issue number2
Publication statusPublished - 1999 Dec 1
Externally publishedYes

Keywords

  • Apoptosis
  • Lactacystin
  • Myogenesis
  • Proteasome

ASJC Scopus subject areas

  • Genetics

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