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ARHGEF17/TEM4 regulates the cell cycle through control of G1 progression

Diogjena Katerina Prifti1,2,3, Annie Lauzier1,2,3, Chantal Garand1,2,3

  • 1Centre de Recherche du Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Axe de Réproduction, Santé de la Mère et de l'Enfant , Québec, Canada.

The Journal of Cell Biology
|February 4, 2025
PubMed

Insights

The guanine nucleotide exchange factor ARHGEF17 (TEM4) regulates cell cycle progression. TEM4 depletion causes defects in mitosis and G1/S transition by impacting YAP and cyclin B expression.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Rho GTPases are key regulators of cellular functions, including cell cycle progression.
  • Upstream regulators of Rho GTPase functions are not fully understood.
  • ARHGEF17 (TEM4) is a guanine nucleotide exchange factor (GEF) involved in cell migration and the mitotic checkpoint.

Purpose of the Study:

  • To investigate the role of TEM4 in regulating the cell cycle.
  • To elucidate the molecular mechanisms by which TEM4 influences cell cycle progression.

Main Methods:

  • Depletion of TEM4 using specific techniques.
  • Analysis of cell cycle progression, mitotic entry, spindle morphology, and actin cytoskeleton.
  • Assessment of YAP and cyclin B (CCNB1) expression levels.
  • Rescue experiments using cyclin B overexpression.

Main Results:

  • TEM4 depletion causes defects in mitotic entry, duration, spindle morphology, and orientation.
  • TEM4 insufficiency leads to excessive cortical actin polymerization and cell rounding.
  • TEM4-depleted cells exhibit G1 delay due to decreased YAP expression.
  • Mitotic defects in TEM4-depleted cells are linked to reduced cyclin B levels.
  • Overexpression of cyclin B rescues mitotic progression and chromosome segregation defects.

Conclusions:

  • TEM4 is crucial for proper cell cycle progression, particularly the G1/S transition.
  • TEM4 regulates G1/S transition through modulation of YAP expression.
  • TEM4 influences mitotic progression via regulation of cyclin B (CCNB1) expression.
  • This study identifies TEM4 as the first GEF controlling Rho GTPase-mediated regulation of the G1/S phase.

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