Chlamydia trachomatis plasmid-encoded protein Pgp3 inhibits apoptosis via the PI3K-AKT-mediated MDM2-p53 axis
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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.
KeywordsChlamydia trachomatis Pgp3 Apoptosis PI3K/AKT MDM2 p53
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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Conflict of interest
All authors declare that they have no conflict of interest.
- 13.Thomas NS, Lusher M, Storey CC, Clarke IN (1997) Plasmid diversity in Chlamydia. Microbiol 143(Pt 6):1847–1854Google Scholar
- 17.Cao W, Zou Y, Su S, He Z, Liu Y, Huang Q, Li Z (2015) Chlamydial plasmid-encoded protein pORF5 induces production of IL-1beta and IL-18 via NALP3 inflammasome activation and p38 MAPK pathway. Int J Clin Exp Med 8(11):20368–20379Google Scholar
- 24.Song L, Carlson JH, Whitmire WM, Kari L, Virtaneva K, Sturdevant DE, Watkins H, Zhou B, Sturdevant GL, Porcella SF, McClarty G, Caldwell HD (2013) Chlamydia trachomatis plasmid-encoded Pgp4 is a transcriptional regulator of virulence-associated genes. Infect Immun 81(3):636–644CrossRefGoogle Scholar