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 beta-transducin-repeat containing protein-1 and 2 (beta TrCP1/2). These interactions involve a phosphodegron (DpSGX(2-4)pS) found in beta TrCP substrates. TAg stability is unaltered, suggesting TAg is a pseudo-substrate. beta TrCP and TAg co-localize in the cytoplasm, and a functional SCF complex is required. We examined whether TAg influences the levels of beta-catenin, a beta TrCP substrate. We were unable to demonstrate that TAg elevates beta-catenin as previously reported, and a mutant TAg unable to bind beta TrCP also had no detectable effect on beta-catenin stability. Results presented in this study link JCV TAg to the cellular degradation complex, SCP beta TrCP1/2. Proteasomal degradation is essential for proper regulation of cellular functions, and interference with proteasomal pathways highlights possible JCV pathogenic and oncogenic mechanisms. (C) 2010 Elsevier Inc. All rights reserved.