Roles of the PDZ‐binding motif of HPV 16 E6 protein in oncogenic transformation of human cervical keratinocytes

• DOI: 10.1111/cas.13264
• Publication Date: 2017-04-25T18:56:38Z
• Authors: Yuki Yoshimatsu; Tomomi Nakahara; Katsuyuki Tanaka; Yuki Inagawa; Mako Narisawa‐Saito; Takashi Yugawa; Shin‐ichi Ohno; Masatoshi Fujita; Hitoshi Nakagama; Tohru Kiyono
• Keywords: PDZ domain; HRAS; HEK 293 cells

The high‐risk human papillomavirus E6 proteins have been shown to interact with and lead degradation of PDZ ‐domain‐containing through its carboxy‐terminal motif. This ‐binding motif plays important roles in transformation cultured cells carcinogenesis E6‐transgenic mice. However, biological effects on the natural host not elucidated. We examined an vitro model for cervical cancer, which E7 together activated HRAS ( G 12V ) can induce tumorigenic normal keratinocytes. In this model, E6Δ151 mutant, is defective binding domains, almost lost ability, whereas SAT p53 showed activity close wild‐type E6. Interestingly, we found decreased expression PAR 3 E6‐expressing independently AP , has previously recognized. Therefore, knocked down several ‐domain containing including keratinocytes expressing E7, examine whether depletion these restore ability. Single knockdown SCRIB MAGI 1 or significantly but partially restored combinatorial cooperatively additional further enhanced ability surpassing that induced by These data highlight importance protein downregulation