title: Ubiquitination and the ubiquitin - proteasome system in the pathogenesis and treatment of squamous head and neck carcinoma.
abstract: 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.
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Sault Area Hospital, 750 Great Northern Rd, Sault Ste Marie, ON P6B OA8, Canada. ivoutsadakis@yahoo.com.
authors.forename: Ioannis A
authors.initials: IA
authors.lastname: Voutsadakis
mesh_terms: D006258:Head and Neck Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000628:therapy; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex
keywords: Head and neck carcinoma; carcinogenesis; review; squamous; ubiquitin ligases; ubiquitin-proteasome system; ubiquitination