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BioMed Research International
Volume 2013 (2013), Article ID 369712, 9 pages
http://dx.doi.org/10.1155/2013/369712
Review Article

PDZ Domains and Viral Infection: Versatile Potentials of HPV-PDZ Interactions in relation to Malignancy

Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo 113-8655, Japan

Received 15 May 2013; Revised 9 July 2013; Accepted 31 July 2013

Academic Editor: Edouard Cantin

Copyright © 2013 Kazunori Nagasaka et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Cervical cancer is caused by high-risk human papillomaviruses (HPVs), and a unique characteristic of these is a PDZ ( SD-95/ lg/ O-1-)binding motif in their E6 proteins. Through this motif HPV E6 interacts with a variety of PDZ domain-containing proteins and targets them mainly for degradation. These E6-PDZ interactions exhibit extraordinarily different functions in relation to HPV-induced malignancy, depending upon various cellular contexts; for example, Dlg and Scrib show different distribution patterns from what is seen in normal epithelium, both in localization and in amount, and their loss may be a late-stage marker in malignant progression. Recent studies show that interactions with specific forms of the proteins may have oncogenic potential. In addition, it is interesting that PDZ proteins make a contribution to the stabilization of E6 and viral episomal maintenance during the course of HPV life cycle. Various posttranslational modifications also greatly affect their functions. Phosphorylation of hDlg and hScrib by certain kinases regulates several important signaling cascades, and E6-PDZ interactions themselves are regulated through PKA-dependent phosphorylation. Thus these interactions naturally have great potential for both predictive and therapeutic applications, and, with development of screening tools for identifying novel targets of their interactions, comprehensive spatiotemporal analysis is currently underway.