HPV16 E6 and Chlamydia trachomatis Pgp3 proteins inhibit TNF-α-induced apoptosis through Daxx-mediated MDM2-p53 pathway.

Abstract

Background and aims: As a common pathogen of sexually transmitted diseases, Chlamydia trachomatis (C. trachomatis) may be a cofactor in the progression of cervical cancer induced by persistent HPV infection, but its molecular mechanism is unclear. The aim of this study is to explore whether HPV16 E6 and C. trachomatis Pgp3 proteins inhibit apoptosis through the Daxx-mediated MDM2-p53 pathway, in order to reveal the potential mechanism of their synergistic effects.

Methods: The HeLa cell model was used to analyze the effects of HPV16 E6 and Pgp3 proteins on Daxx expression and the MDM2-p53 pathway, combined with interfering with Daxx, TNF-α-induced apoptosis assay and Nutlin-3a treatment to validate the function of key molecules.

Results: HPV16 E6 and C. trachomatis Pgp3 proteins can upregulate the expression of Daxx proteins individually or synergistically, and the inhibitory on TNF-α-induced apoptosis may be superimposed. Interference with Daxx partially reversed the apoptosis inhibition of HPV16 E6 and Pgp3, suggesting that it may act by promoting MDM2 phosphorylation and p53 degradation. Moreover, Nutlin-3a treatment can attenuate the apoptosis inhibitory of HPV16 E6 and Pgp3, further supporting the involvement of MDM2-p53 pathway.

Conclusions: This study suggests that HPV16 E6 and C. trachomatis Pgp3 proteins can inhibit TNF-α-induced apoptosis through Daxx-mediated MDM2-p53 pathway, which may provide a mechanistic foundation for the study of HPV16 and C. trachomatis co-infection on cervical cancer progression.