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Overcoming inhibitions: subversion of CKI function by viral cyclins

C Swanton1, G L Card, D Mann

  • 1Gene Regulation Laboratory, ICRF, PO Box 123, Lincoln's Inn Fields, London, UK WC2A 3PX.

Trends in Biochemical Sciences
|April 27, 1999
PubMed

Insights

DNA tumor viruses manipulate the cell cycle for replication. Herpesviruses encode a cyclin to override inhibitors, disrupting the critical G1-S phase transition balance.

Area of Science:

  • Cellular biology
  • Virology
  • Molecular biology

Background:

  • DNA tumor viruses alter host cell cycle regulation for replication.
  • The G1-S phase transition is a critical control point in the mammalian cell cycle.
  • This transition is regulated by the balance between cyclin-dependent kinase (CDK) complexes and their inhibitors.

Purpose of the Study:

  • To investigate how DNA tumor viruses, specifically herpesviruses, deregulate the cell cycle.
  • To understand the mechanism by which herpesviruses disrupt the G1-S phase transition.
  • To identify viral factors that contribute to cell cycle dysregulation.

Main Methods:

  • Analysis of cell cycle regulatory proteins in virus-infected cells.
  • Investigating the role of viral cyclins in complex formation with host CDKs.
  • Assessing the impact of viral cyclins on the activity of cell cycle inhibitors.

Main Results:

  • Herpesviruses encode their own cyclins.
  • These viral cyclins form active complexes with host CDK partners.
  • The viral cyclin-CDK complexes remain active despite the presence of high levels of G1-specific inhibitors.

Conclusions:

  • Herpesviruses actively disrupt the host cell G1-S phase checkpoint.
  • Viral cyclins are key mediators of this disruption, overriding normal inhibitory controls.
  • This viral strategy ensures a favorable cellular environment for viral replication.

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