Interaction and co-localization of JC virus large T antigen and the F-box protein β-transducin-repeat containing protein.

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. Copyright Â