p53 inhibits JC virus DNA replication in vivo and interacts with JC virus large T-antigen

C Staib1, J Pesch, R Gerwig

  • 1Institut für Biochemie, Universität Würzburg, Germany.

Virology
|May 1, 1996
PubMed

Insights

The tumor suppressor protein p53 inhibits human neurotropic polyomavirus JC (JCV) DNA replication. This inhibition occurs through direct interaction between p53 and the JCV large T-antigen.

Area of Science:

  • Virology
  • Molecular Biology
  • Oncology

Background:

  • DNA replication is crucial for the JC polyomavirus (JCV) life cycle.
  • The tumor suppressor protein p53 plays a role in regulating cellular processes.

Purpose of the Study:

  • To investigate the effect of human and murine p53 on JCV DNA replication.
  • To determine the mechanism by which p53 inhibits JCV DNA replication.

Main Methods:

  • In vivo studies using deletion mutants of murine p53 and human p53 point mutants.
  • Analysis of JCV large T-antigen expression and protein-protein interactions.

Main Results:

  • Both human and murine p53 dose-dependently inhibited JCV DNA replication.
  • The inhibitory effect of p53 required its central conserved region.
  • p53 mutants that failed to inhibit replication also lost direct interaction with JCV large T-antigen.

Conclusions:

  • p53 directly inhibits JCV DNA replication.
  • The interaction between p53 and JCV large T-antigen is essential for this inhibition.

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