Toxoplasma gondii exploits UHRF1 and induces host cell cycle arrest at G2 to enable its proliferation

Cell Microbiol. 2008 Apr;10(4):908-20. doi: 10.1111/j.1462-5822.2007.01093.x. Epub 2007 Nov 14.

Abstract

Toxoplasma gondii is an obligate intracellular parasite that causes severe disease in humans. It is able to infect all nucleated mammalian cells leading to lifelong persistence of the parasite in the host. Here, we studied the effect of T. gondii infection on host cell proliferation and explored the molecular mechanisms involved in host cell cycle progression. We found that T. gondii induced G1/S transition in host cells in the presence of UHRF1, followed by G2 arrest after cyclin B1 downregulation which is probably the major cause of the arrest. Other molecules at the G2/M checkpoint including p53, p21 and Cdk1 were normally regulated. Interestingly, while parasite proliferation was normal in cells that were in the G2 phase, it was suppressed in G1-arrested cells induced by UHRF1-siRNA, indicating the importance of the G2 phase via UHRF1-induced G1/S transition for T. gondii growth.

MeSH terms

  • Animals
  • Blotting, Western
  • CCAAT-Enhancer-Binding Proteins / genetics
  • CCAAT-Enhancer-Binding Proteins / metabolism*
  • CDC2 Protein Kinase / genetics
  • CDC2 Protein Kinase / metabolism
  • Cell Cycle / physiology*
  • Cell Line
  • Cell Proliferation*
  • Cyclin B / genetics
  • Cyclin B / metabolism
  • Cyclin B1
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Flow Cytometry
  • G2 Phase / physiology*
  • Host-Parasite Interactions
  • Humans
  • Immunohistochemistry
  • Immunoprecipitation
  • RNA, Small Interfering / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Toxoplasma / growth & development
  • Toxoplasma / physiology*
  • Transfection
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • CCAAT-Enhancer-Binding Proteins
  • CCNB1 protein, human
  • Cyclin B
  • Cyclin B1
  • Cyclin-Dependent Kinase Inhibitor p21
  • RNA, Small Interfering
  • Tumor Suppressor Protein p53
  • UHRF1 protein, human
  • CDC2 Protein Kinase