title: Interaction and co-localization of JC virus large T antigen and the F-box protein β-transducin-repeat containing protein.
abstract: Lytic infection and transformation of cultured cells by JC virus (JCV) require five tumor proteins, which interact with factors regulating critical cellular processes. We demonstrate that JCV large T antigen (TAg) binds the F-box proteins β-transducin-repeat containing protein-1 and 2 (βTrCP1/2). These interactions involve a phosphodegron (DpSGX(2-4)pS) found in βTrCP substrates. TAg stability is unaltered, suggesting TAg is a pseudo-substrate. βTrCP and TAg co-localize in the cytoplasm, and a functional SCF complex is required. We examined whether TAg influences the levels of β-catenin, a βTrCP substrate. We were unable to demonstrate that TAg elevates β-catenin as previously reported, and a mutant TAg unable to bind βTrCP also had no detectable effect on β-catenin stability. Results presented in this study link JCV TAg to the cellular degradation complex, SCF(βTrCP1/2). Proteasomal degradation is essential for proper regulation of cellular functions, and interference with proteasomal pathways highlights possible JCV pathogenic and oncogenic mechanisms.
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Marta M
authors.initials: MM
authors.lastname: Reviriego-Mendoza
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Frisque
mesh_terms: D000914:Antibodies, Viral; D000957:Antigens, Viral, Tumor / Q000378:metabolism*; D002460:Cell Line; D003593:Cytoplasm; D006801:Humans; D007577:JC Virus / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D013539:Simian virus 40 / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin; D044844:beta-Transducin Repeat-Containing Proteins / Q000378:metabolism*
chemical_list: D000914:Antibodies, Viral; D000957:Antigens, Viral, Tumor; C471644:BTRC protein, human; D051176:beta Catenin; D044844:beta-Transducin Repeat-Containing Proteins