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TORC1 regulates G1/S transition and cell proliferation via the E2F homologs MBF and SBF in yeast

Shamsul Morshed1, Tsukasa Shibata2, Kayoko Naito3

  • 1Graduate School of Science and Technology, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka, 422-8021, Japan.

Biochemical and Biophysical Research Communications
|June 20, 2020
PubMed

Insights

The target of rapamycin complex 1 (TORC1) kinase directly controls yeast cell cycle progression by regulating MBF and SBF transcription factors. This regulation ensures G1/S transition occurs appropriately with nutrient availability.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Yeast Genetics

Background:

  • MBF (Mbp1/Swi6) and SBF (Swi4/Swi6) are yeast E2F homologs crucial for G1/S cell cycle transition.
  • TORC1 kinase promotes G1/S transition by upregulating Cln3, which activates MBF and SBF under favorable nutrient conditions.

Purpose of the Study:

  • To investigate the direct regulatory role of TORC1 in G1/S transition via MBF and SBF.
  • To elucidate the molecular mechanisms underlying TORC1-mediated regulation of these transcription factors.

Main Methods:

  • Rapamycin treatment to inactivate TORC1.
  • Analysis of protein levels of MBF and SBF components (Mbp1, Swi4, Swi6).
  • Investigating Mbp1 degradation pathway using SCF-Grr1 and proteasome inhibitors.
  • Identification of a PEST-like degron in Mbp1.
  • Phenotypic analysis of mutant cells with unstable Mbp1.

Main Results:

  • Rapamycin treatment led to the loss of Mbp1 and Swi4, but not Swi6.
  • TORC1 inactivation accelerated the degradation of Mbp1 and Swi4.
  • Mbp1 degradation was dependent on the SCF-Grr1 ubiquitin ligase and proteasomes.
  • A PEST-like degron in Mbp1 was identified, and its mutation conferred rapamycin hypersensitivity and G1 cell accumulation.

Conclusions:

  • TORC1 directly regulates G1/S transition by controlling the stability of MBF and SBF transcription factors.
  • Nutrient availability influences cell cycle progression through TORC1-mediated regulation of Mbp1 and Swi4 degradation.
  • This study reveals a direct link between nutrient sensing and cell cycle control at the level of key transcription factors.
Keywords:
E2FMBFMbp1SBFSwi4TORC1

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