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

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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.

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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).

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    Authors and Affiliations

    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 Study, University of South China, Hengyang, 421001, Hunan, People’s Republic of China

      Yan Zou, Wenbo Lei, Shengmei Su, Jichang Bu & Zhongyu Li

    2. Department of General Surgery, The First Affiliated Hospital of University of South China, Hengyang, 421001, Hunan, People’s Republic of China

      Qiulin Huang

    3. Clinical Laboratory, Maternity and Child Health Care Hospital in Xiangtan, Xiangtan, 411100, Hunan, People’s Republic of China

      Yan Zou & Shunxin Zhu

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    1. Yan Zou
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    Correspondence to Qiulin Huang or Zhongyu Li.

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    Wenbo Lei contributed equally to this work.

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    Zou, Y., Lei, W., Su, S. et al. Chlamydia trachomatis plasmid-encoded protein Pgp3 inhibits apoptosis via the PI3K-AKT-mediated MDM2-p53 axis. Mol Cell Biochem 452, 167–176 (2019). https://doi.org/10.1007/s11010-018-3422-9

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