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Assay for Adhesion and Agar Invasion in S. cerevisiae
04:36

Assay for Adhesion and Agar Invasion in S. cerevisiae

Published on: November 8, 2006

Adenovirus E4orf4 protein induces PP2A-dependent growth arrest in Saccharomyces cerevisiae and interacts with the

D Kornitzer1, R Sharf, T Kleinberger

  • 1The Gonda Center of Molecular Microbiology, The Bruce Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel.

The Journal of Cell Biology
|July 27, 2001
PubMed

Insights

Adenovirus E4orf4 protein causes irreversible cell cycle arrest in yeast by inhibiting the anaphase-promoting complex/cyclosome (APC/C) via protein phosphatase 2A (PP2A). This conserved mechanism also induces G2/M arrest in mammalian cells.

Area of Science:

  • Molecular and Cellular Biology
  • Virology
  • Yeast Genetics

Background:

  • Adenovirus early region 4 open reading frame 4 (E4orf4) protein induces apoptosis in mammalian cells.
  • This process is independent of p53 and dependent on protein phosphatase 2A (PP2A).

Purpose of the Study:

  • To investigate the conserved function of E4orf4 in cell cycle regulation.
  • To elucidate the mechanism of E4orf4-induced growth arrest in Saccharomyces cerevisiae.

Main Methods:

  • Yeast genetics and cell cycle analysis.
  • Analysis of reactive oxygen species accumulation.
  • Synthetic lethality studies with cell division cycle mutants.
  • Investigation of protein phosphatase 2A (PP2A) and anaphase-promoting complex/cyclosome (APC/C) interactions.

Main Results:

  • E4orf4 induces irreversible G2/M phase cell cycle arrest in yeast.
  • This arrest requires yeast PP2A-Cdc55 and leads to reactive oxygen species accumulation.
  • E4orf4 is synthetically lethal with mutants in key mitotic regulators (Cdc28/Cdk1, APC/C).
  • E4orf4 directly targets PP2A to the APC/C, inhibiting its activity and activating Cdc28/Cdk1.
  • E4orf4 also induces G2/M arrest in mammalian cells, preceding apoptosis.

Conclusions:

  • E4orf4 utilizes a conserved mechanism involving PP2A and APC/C to induce cell cycle arrest.
  • The findings reveal a conserved role for E4orf4 in regulating cell division across species.
  • E4orf4's ability to inhibit APC/C and induce G2/M arrest highlights its potential as a tool for studying cell cycle control.

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