PP2A-dependent transactivation of the cyclin A promoter by SV40 ST is mediated by a cell cycle-regulated E2F site

Christine Skoczylas1, Berthold Henglein, Kathleen Rundell

  • 1Department of Microbiology-Immunology, Northwestern University, 303 E. Chicago Avenue, Chicago, IL 60611, USA.

Virology
|February 1, 2005
PubMed

Insights

Simian Virus 40 (SV40) small-t antigen (ST) drives cell proliferation and enhances transformation. ST interacts with protein phosphatase 2A (PP2A) to activate the cyclin A promoter.

Area of Science:

  • Virology
  • Molecular Biology
  • Cell Biology

Background:

  • Simian Virus 40 (SV40) is a DNA tumor virus.
  • The SV40 small-t antigen (ST) is implicated in viral oncogenesis and cell cycle regulation.
  • Understanding ST's molecular mechanisms is crucial for cancer research.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which SV40 ST regulates cell proliferation.
  • To identify the specific cellular targets and pathways modulated by ST.
  • To investigate the role of protein phosphatase 2A (PP2A) in ST-mediated transactivation.

Main Methods:

  • Analysis of SV40 ST interactions with cellular proteins.
  • Reporter gene assays to measure promoter activity (e.g., cyclin A promoter).
  • Cell cycle analysis and proliferation assays.

Main Results:

  • SV40 ST enhances cell proliferation and transformation, partly by targeting p27 and cyclin A.
  • ST-mediated transactivation of the cyclin A promoter requires interaction with PP2A.
  • This activation occurs via a cell cycle-regulated E2F site on the cyclin A promoter.

Conclusions:

  • SV40 ST utilizes PP2A to modulate the cyclin A promoter, contributing to cell cycle dysregulation.
  • The findings provide insights into viral mechanisms of cell proliferation and transformation.
  • ST's interaction with PP2A represents a key step in SV40-induced oncogenesis.

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