TY - JOUR T1 - Ubiquitination and the Ubiquitin – Proteasome System in the Pathogenesis and Treatment of Squamous Head and Neck Carcinoma JF - Anticancer Research JO - Anticancer Res SP - 3527 LP - 3541 VL - 33 IS - 9 AU - IOANNIS A. VOUTSADAKIS Y1 - 2013/09/01 UR - http://ar.iiarjournals.org/content/33/9/3527.abstract N2 - Squamous carcinomas of the head and neck area are carcinomas that were traditionally associated with alcohol and tobacco abuse. More recently, a pathogenic relationship of oncogenic human papilloma viruses (HPV) with head and neck cancer of the oropharynx and the base of the tongue has been revealed. Two proteins of HPV, E6 and E7, are involved in neoplastic transformation not only in the head and neck but in other locations, where these epitheliotropic viruses cause carcinomas, such as the uterine cervix and the anal region. The E6 viral protein associates with cellular E3 ubiquitin ligase E6-AP and promotes degradation of tumour suppressor p53 by the proteasome. This molecular event reveals the important role that the ubiquitin-proteasome system (UPS) plays in the pathogenesis of head and neck cancer. The role of this system in head and neck carcinogenesis is not restricted to the destruction of p53 but extends to most, if not all, signaling pathways that regulate carcinogenesis in this location. These roles are reviewed here and implications for treatment are discussed. ER -