Polyomavirus middle-T antigen lacking a membrane anchor sequence accumulates in the nucleus

Three proteins expressed early in the replicative cycle of polyomavirus also play an essential role during virused-mediated tumorigenesis. One of the proteins, middle-T antigen, has been shown to bind cellular proteins involved in cell signalling such as c-Src, phosphatase 2A, phosphatidylinositol 3-kinase and SHC. Association of middle-T antigen with cellular membranes has been shown to be essential for middle-T-mediated cell transformation. A mutant virus encoding a truncated form of middle-T lacking a carboxy-terminal hydrophobic sequence mediating membrane association is not oncogenic. This mutant middle-T still binds phosphatase 2A through amino-terminal sequences common to small- and middle-T and is localized in the nucleus, although the protein does not contain a classical nuclear targeting sequence. Mutations introduced into the amino-terminal domain affecting the ability of truncated middle-T to bind phosphatase 2A prevented accumulation of the protein in the nucleus and led to localization in the cytoplasm. This suggests that nuclear localization of truncated middle-T may be a consequence of binding to phosphatase 2A.