TRANSFORMATION BY MIDDLE T-ANTIGENS

The polyomaviruses, members of the papovavirus group of DNA tumor viruses, encode in the 'early' region of the genome, three proteins involved in transformation, the tumor (or T) antigens, called large (LT), middle (mT) and small (sT) T. LT is required for establishment of primary fibroblasts, and sT promotes the efficiency of transformation both in vivo and in vitro, but it is mT that carries the transforming ability. The mTs of the two known polyomaviruses, from mouse and hamster, possess no intrinsic catalytic activity, but rather interact with and change the activity of several cellular proteins, including Src family protein tyrosine kinases, protein phosphatase 2A, phosphatidylinositol 3-kinase and Shc. Same of these proteins are also involved in signal transduction events elicited by growth factors. Like activated growth receptors, mT brings its associated proteins to a membranous environment. Transformation by mT might result not only from allosteric effects of mT on its interacting proteins but also as a result of their subcellular relocalization.