Simian virus 40 large T antigen affects the Saccharomyces cerevisiae cell cycle and interacts with p34CDC28

M Nacht1, S I Reed, J C Alwine

  • 1Department of Microbiology, University of Pennsylvania, School of Medicine, Philadelphia 19104-6142.

Journal of Virology
|February 1, 1995
PubMed

Insights

Simian virus 40 tumor antigen disrupts yeast cell growth by interacting with cell cycle proteins. This interaction alters kinase function, causing a G1 to S phase transition delay.

Area of Science:

  • Molecular Biology
  • Cell Cycle Regulation
  • Virology

Background:

  • Simian virus 40 tumor (T) antigen is a viral oncoprotein known to affect cellular protein function and growth control.
  • Understanding T antigen's interactions is crucial for deciphering its oncogenic mechanisms.

Purpose of the Study:

  • To investigate the impact of T antigen on cell growth control in Saccharomyces cerevisiae.
  • To identify cellular proteins that functionally interact with T antigen.

Main Methods:

  • Expression of T antigen in budding yeast (Saccharomyces cerevisiae).
  • Co-immunoprecipitation and in vivo cross-linking to detect protein interactions.
  • Kinase assays using immunoprecipitated complexes and histone H1 substrate.

Main Results:

  • Yeast cells expressing T antigen exhibited morphological changes and growth inhibition, with a delay in G1 to S phase progression.
  • T antigen directly binds to p34CDC28 and p34CDC2Hs, key regulators of the G1 to S transition.
  • T antigen-bound p34CDC28 complexes showed altered kinase activity, including phosphorylation of a novel 60-kDa protein.

Conclusions:

  • T antigen interacts with yeast cell cycle proteins, specifically p34CDC28.
  • This interaction leads to altered kinase function of p34CDC28-containing complexes.
  • These molecular events correlate with observed cell cycle alterations in yeast, specifically at the G1 to S transition.

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