Fig. 3.

The contribution of HPV E6 PBM target selection to HPV-induced carcinogenesis. The evolutionary acquisition of a PBM on HPV E6 proteins is probably associated with the colonizing of a new niche—and is associated with Dlg1 binding, but not with oncogenicity. Further adaptations of the PBM allow binding to more diverse polarity proteins, thus targeting more pathways to enhance the viral life cycle, but potentially also perturbing controls of epithelial differentiation, seen clinically as CIN I (cervical intraepithelial neoplasia, grade 1). Further adaptation of the PBM leads to a more flexible target binding profile, greater polarity perturbation, mislocalization or deletion of PDZ polarity proteins, and the acquisition of pro-oncogenic properties by Dlg1 and hScrib, manifest as CIN III (cervical intraepithelial neoplasia, grade 3) and its potential progression to cancer. Restoration of functional polarity proteins can lead to apoptosis of cervical cancer cells and may indicate a possible direction for therapeutic strategies.