Human Papillomavirus E6 interaction with cellular PDZ domain proteins modulates YAP nuclear localization

Abstract

HPV E6 oncoproteins associate with cellular PDZ proteins. In addition to previously identified cellular PDZ proteins, we found association of the HPV16 E6 PBM with the Dystrophin Glycoprotein Complex, LRCC1, and SLC9A3R2. HPV18 E6 had additional associations when lysates from adenomatous cell lines were used including LRPPRC, RLGAPB, EIF3A, SMC2 and 3, AMOT, AMOTL1, and ARHGEF1; some of these cellular PDZ proteins are implicated in the regulation of the YAP1 transcriptional co-activator. In keratinocytes, nuclear translocation of YAP1 was promoted by the complete HPV-16 genome, or by expression of the individual E6 or E7 oncoproteins; the activity of E6 required an intact PBM at the carboxy-terminus. This work demonstrates that E6 association with cellular PDZ proteins promotes the nuclear localization of YAP1. The ability of E6 to promote the nuclear transport of YAP1 thus identifies an E6 activity that could contribute to the transformation of cells by E6.

WITHDRAWN: Interplay between cancer cells and M2 macrophages is necessary for miR-550a-3-5p down-regulation-mediated HPV-positive OSCC progression

“…Several studies have also showed that aberrant YAP accumulation in the nucleus of cancer cells was found in both cervical cancer and HPV-positive OSCC, and HPV-positive patients with higher YAP levels usually had a more advanced stage (54)(55)(56). Moreover, Webb Strickland and colleagues have reported that E6 oncoprotein could associate with cellular PDZ domain proteins to promote the nuclear localization of YAP (57). In our study, we put forward a pathway in which miR-550a-3-5p, down-regulated by E6 oncoprotein, inhibited YAP but not TAZ in HPV-positive OSCC.…”

RETRACTED ARTICLE: Interplay between cancer cells and M2 macrophages is necessary for miR-550a-3-5p down-regulation-mediated HPV-positive OSCC progression

“…Several studies have also showed that aberrant YAP accumulation in the nucleus of cancer cells was found in both cervical cancer and HPVpositive OSCC, and HPV-positive patients with higher YAP levels usually had a more advanced stage [60][61][62]. Moreover, Webb Strickland and colleagues have reported that E6 oncoprotein could associate with cellular PDZ domain proteins to promote the nuclear localization of YAP [63]. In our study, we put forward a pathway in which miR-550a-3-5p, downregulated by E6 oncoprotein, inhibited YAP but not TAZ in HPV-positive OSCC.…”

HPV E6 Protein Associated SOX21-AS1 Promotes YAP/TAZ Activation by Attenuating YAP1 Ubiquitination in Human Cervical Cancer

“…A previous study has shown that E6 protein can promote YAP1/TAZ transnational activity by binding to the PDZ domain of TAZ [17]. We found that E6 level was positively related to SOX21-AS1.…”