Simian virus 40 small t antigen activates the carboxyl-terminal transforming p53-binding domain of large T antigen.
Expression of the simian virus 40 large T antigen (large T) in F111 rat fibroblasts generated only minimal transformants (e.g., F5 cells). Interestingly, F111-derived cells expressing only an amino-terminal fragment of large T spanning amino acids 1 to 147 (e.g., FR3 cells), revealed the same minimal transformed phenotype as F111 cells expressing full-length large T. This suggested that in F5 cells the transforming domain of large T contained within the C-terminal half of the large T molecule, and spanning the p53 binding domain, was not active. Progression to a more transformed phenotype by coexpression of small t antigen (small t) could be achieved in F5 cells but not in FR3 cells. Small-t-induced progression of F5 cells correlated with metabolic stabilization of p53 in complex with large T: whereas in F5 cells the half-life of p53 in complex with large T was only slightly elevated compared with that of (uncomplexed) p53 in parental F111 cells or that in FR3 cells, coexpression of small t in F5 cells led to metabolic stabilization and to high-level accumulation of p53 complexed to large T. In contrast, coexpression of small t had no effect on p53 stabilization or accumulation in FR3 cells. This finding strongly supports the assumption that the mere physical interaction of large T with p53, and thus p53 inactivation, in F5 cells expressing large T only does not reflect the main transforming activity of the C-terminal transforming domain of large T. In contrast, we assume that the transforming potential of this domain requires activation by a cellular function(s) which is mediated by small t and correlates with metabolic stabilization of p53.
Zerrahn
J
J
Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg, Germany.
Tiemann
F
F
Deppert
W
W
D000818:Animals; D000957:Antigens, Viral, Tumor / Q000378:metabolism*; D002472:Cell Transformation, Viral; D005347:Fibroblasts / Q000821:virology; D010766:Phosphorylation; D051381:Rats; D017421:Sequence Analysis; D013539:Simian virus 40 / Q000276:immunology*
D000957:Antigens, Viral, Tumor