title: Ubiquitination and proteasome degradation of the E6 proteins of human papillomavirus types 11 and 18.
abstract: Human papillomaviruses (HPVs) are aetiological agents for genital warts and cervical cancer, the different pathologies of which are dependent on the type of HPV infection. Oncogenic HPV types associated with cancer are carcinogens by virtue of their oncogene products, which target key regulators of cell proliferation and apoptosis. The viral E6 protein from oncogenic HPV types plays a central role in carcinogenesis by exploiting the cellular proteasome degradation pathway in order to mediate the degradation of cellular proteins, most notably the prototype tumour suppressor protein p53. Much less is known about the cellular targets of E6 from the non-oncogenic HPV types associated with genital warts. It is also unclear what factors influence the level and stability of the viral E6 proteins in cells. This report demonstrates that both oncogenic and non-oncogenic HPV E6 proteins (from types 18 and 11, respectively) are ubiquitinated and targeted for degradation by the 26S proteasome. E6 domains required for the induction of p53 or DLG degradation, or E6AP binding, are not involved in proteasome-mediated degradation of HPV-18 E6. These results provide insight into the cellular modulation of E6 protein levels from both high-risk and low-risk HPV types.
authors.affiliation: Department of Microbiology and Immunology, McGill University, 3775 University Street, Room 511, Montreal, Canada, H3A 2B4.|Institute of Parasitology, MacDonald Campus, McGill University, Montreal, Canada, H9X 3V9.
authors.forename: Deborah
authors.initials: D
authors.lastname: Stewart
authors.affiliation: Lady Davis Institute for Medical Research, McGill University, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Canada, H3T 1E2.
authors.forename: Shirin
authors.initials: S
authors.lastname: Kazemi
authors.affiliation: Lady Davis Institute for Medical Research, McGill University, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Canada, H3T 1E2.
authors.forename: Suiyang
authors.initials: S
authors.lastname: Li
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34012 Trieste, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Massimi
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34012 Trieste, Italy.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Banks
authors.affiliation: Lady Davis Institute for Medical Research, McGill University, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Canada, H3T 1E2.
authors.forename: Antonis E
authors.initials: AE
authors.lastname: Koromilas
authors.affiliation: Department of Microbiology and Immunology, McGill University, 3775 University Street, Room 511, Montreal, Canada, H3A 2B4.
authors.forename: Greg
authors.initials: G
authors.lastname: Matlashewski
mesh_terms: D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000502:physiology*; D004268:DNA-Binding Proteins; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D009097:Multienzyme Complexes / Q000502:physiology*; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C469553:E6 protein, Human papillomavirus type 11; C052603:E6 protein, Human papillomavirus type 18; D008164:Luminescent Proteins; D009097:Multienzyme Complexes; D009856:Oncogene Proteins, Viral; D025801:Ubiquitin; D049452:Green Fluorescent Proteins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex