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Molecular and Cellular Biochemistry

, Volume 452, Issue 1–2, pp 167–176 | Cite as

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

  • Yan Zou
  • Wenbo Lei
  • Shengmei Su
  • Jichang Bu
  • Shunxin Zhu
  • Qiulin HuangEmail author
  • Zhongyu LiEmail author
Article
First Online:

Abstract

Chlamydia trachomatis, the most common human pathogen that causes trachoma and sexually transmitted disease, has developed various strategies for inhibiting host cell apoptosis. Activation of the PI3K (phosphoinositide 3-kinase)/AKT-mediated MDM2 (murine double minute 2)-p53 pathway plays a prominent role in the apoptosis resistance arising from C. trachomatis infection. However, the precise upstream mechanisms by which C. trachomatis activates this pathway have not been adequately investigated. Here, we reveal that the secreted C. trachomatis plasmid-encoded protein Pgp3 inhibits apoptosis in HeLa cells. This process requires the activation of the PI3K/AKT signaling pathway, thereby leading to phosphorylation and nuclear entry of MDM2, and p53 degradation. PI3 K inhibitor LY294002 and MDM2 inhibitor Nutlin-3a block Pgp3-induced inhibition of HeLa cell apoptosis, suggesting a critical role for the PI3K/AKT pathway and its effect on the MDM2-p53 axis in Pgp3 anti-apoptotic activity.

Keywords

Chlamydia trachomatis Pgp3 Apoptosis PI3K/AKT MDM2 p53 
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Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 31470277 and 81102230), Construct Program of the Key Discipline in Hunan Province (No. 2011-76), Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control (No. 2014-5), and Hunan Province Cooperative innovation Center for Molecular Target New Drug Study (No. 2014-405).

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute 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 StudyUniversity of South ChinaHengyangPeople’s Republic of China
  2. 2.Department of General SurgeryThe First Affiliated Hospital of University of South ChinaHengyangPeople’s Republic of China
  3. 3.Clinical LaboratoryMaternity and Child Health Care Hospital in XiangtanXiangtanPeople’s Republic of China

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