title: Interactions of the PDZ-protein MAGI-1 with adenovirus E4-ORF1 and high-risk papillomavirus E6 oncoproteins.
abstract: The oncoproteins of small DNA tumor viruses promote tumorigenesis by complexing with cellular factors intimately involved in the control of cell proliferation. The major oncogenic determinants for human adenovirus type 9 (Ad9) and high-risk human papillomaviruses (HPV) are the E4-ORF1 and E6 proteins, respectively. These seemingly unrelated viral oncoproteins are similar in that their transforming activities in cells depend, in part, on a carboxyl-terminal PDZ domain-binding motif which mediates interactions with the cellular PDZ-protein DLG. Here we demonstrated that both Ad9 E4-ORF1 and high-risk HPV E6 proteins also bind to the DLG-related PDZ-protein MAGI-1. These interactions resulted in MAGI-1 being aberrantly sequestered in the cytoplasm by the Ad9 E4-ORF1 protein or being targeted for degradation by high-risk HPV E6 proteins. Transformation-defective mutant viral proteins, however, were deficient for these activities. Our findings indicate that MAGI-1 is a member of a select group of cellular PDZ proteins targeted by both adenovirus E4-ORF1 and high-risk HPV E6 proteins and, in addition, suggest that the tumorigenic potentials of these viral oncoproteins depend, in part, on an ability to inhibit the function of MAGI-1 in cells.
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Glaunsinger
authors.forename: S S
authors.initials: SS
authors.lastname: Lee
authors.forename: M
authors.initials: M
authors.lastname: Thomas
authors.forename: L
authors.initials: L
authors.lastname: Banks
authors.forename: R
authors.initials: R
authors.lastname: Javier
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D017504:Adenovirus E4 Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins; D005455:Fluorescent Antibody Technique; D051528:Guanylate Kinases; D006207:Half-Life; D009154:Mutation / Q000235:genetics; D009703:Nucleoside-Phosphate Kinase / Q000737:chemistry* / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D015531:Radioimmunoprecipitation Assay; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014162:Transfection
chemical_list: D017504:Adenovirus E4 Proteins; D004268:DNA-Binding Proteins; C101120:E4 protein, Adenovirus 9; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases