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Chlamydia trachomatis plasmid-encoded protein Pgp3 inhibits apoptosis via the PI3K-AKT-mediated MDM2-p53 axis

Yan Zou1,2, Wenbo Lei1, Shengmei Su1

  • 1Institute of Pathogenic Biology, Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, Hunan, People's Republic of China.

Molecular and Cellular Biochemistry
|August 23, 2018
PubMed

Insights

Chlamydia trachomatis protein Pgp3 prevents cell death by activating the PI3K/AKT pathway, leading to MDM2-mediated p53 degradation. This mechanism highlights a key strategy used by the pathogen to evade apoptosis.

Area of Science:

  • Microbiology
  • Cell Biology
  • Molecular Biology

Background:

  • Chlamydia trachomatis is a major human pathogen causing trachoma and STIs.
  • C. trachomatis employs strategies to resist host cell apoptosis.
  • The PI3K/AKT/MDM2-p53 pathway is implicated in C. trachomatis-induced apoptosis resistance.

Purpose of the Study:

  • To investigate the upstream mechanisms by which C. trachomatis activates the PI3K/AKT/MDM2-p53 pathway.
  • To determine the role of the secreted protein Pgp3 in C. trachomatis-mediated apoptosis inhibition.

Main Methods:

  • HeLa cells were treated with C. trachomatis protein Pgp3.
  • Investigated the activation of the PI3K/AKT signaling pathway.
  • Assessed MDM2 phosphorylation and nuclear translocation.
  • Monitored p53 degradation.
  • Utilized PI3K inhibitor LY294002 and MDM2 inhibitor Nutlin-3a.

Main Results:

  • Secreted C. trachomatis protein Pgp3 inhibits apoptosis in HeLa cells.
  • Pgp3 activates the PI3K/AKT signaling pathway.
  • This activation leads to MDM2 phosphorylation, nuclear entry, and subsequent p53 degradation.
  • Inhibitors of PI3K and MDM2 blocked Pgp3-induced apoptosis inhibition.

Conclusions:

  • The C. trachomatis protein Pgp3 utilizes the PI3K/AKT pathway to inhibit apoptosis.
  • Pgp3 promotes MDM2-mediated p53 degradation, contributing to pathogen survival.
  • The PI3K/AKT/MDM2-p53 axis is crucial for Pgp3's anti-apoptotic activity.
Keywords:
ApoptosisChlamydia trachomatisMDM2PI3K/AKTPgp3p53

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