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 virus-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.
Messerschmitt
A
A
Friedrich Miescher-Institute, Basel, Switzerland.
Disela
C
C
Dilworth
S
S
Marti
A G
AG
Ballmer-Hofer
K
K
D016475:3T3 Cells; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000821:virology*; D002467:Cell Nucleus / Q000821:virology*; D051379:Mice; D009154:Mutation; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011485:Protein Binding; D054648:Protein Phosphatase 2; D013329:Structure-Activity Relationship
D000952:Antigens, Polyomavirus Transforming; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2