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Efficient parvovirus replication requires CRL4Cdt2-targeted depletion of p21 to prevent its inhibitory interaction

Richard O Adeyemi1, Matthew S Fuller1, David J Pintel1

  • 1Department of Molecular Microbiology and Immunology, C.S. Bond Life Sciences Center, University of Missouri-Columbia, School of Medicine, Columbia, Missouri, United States of America.

Plos Pathogens
|April 5, 2014
PubMed

Insights

Minute virus of mice (MVM) infection hijacks the CRL4Cdt2 ligase to degrade the p21 protein, which is essential for viral replication. This process allows MVM to overcome p21

Area of Science:

  • Virology
  • Molecular Biology
  • Cellular Biology

Background:

  • Minute virus of mice (MVM) is a parvovirus that replicates efficiently by inducing a DNA damage response in host cells.
  • The p53-p21 pathway is activated during MVM infection, but p21 protein levels remain low, suggesting a mechanism for its regulation.

Purpose of the Study:

  • To investigate the mechanism by which p21 protein levels are maintained low during MVM infection.
  • To elucidate the role of the CRL4Cdt2 E3-ubiquitin ligase and PCNA in MVM replication and p21 regulation.

Main Methods:

  • Immunofluorescence to observe the localization of CRL4Cdt2 and PCNA.
  • Co-immunoprecipitation to assess protein interactions.
  • Analysis of MVM replication in the presence of wild-type and mutant p21 proteins.

Main Results:

  • CRL4Cdt2 ligase relocalizes to MVM replication centers during infection.
  • PCNA serves as a platform for CRL4Cdt2 to target p21 for degradation.
  • p21 interaction with PCNA is crucial for its targeting to CRL4Cdt2, and its degradation is required for efficient MVM replication.

Conclusions:

  • MVM infection utilizes CRL4Cdt2-mediated degradation of p21 to promote viral replication.
  • PCNA plays a dual role in MVM infection: facilitating p21 degradation and being antagonized by p21.

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