Polyomavirus large- and small-T relieve middle-T-induced cell cycle arrest in normal fibroblasts

Abstract

Papovavirus tumour antigens have been widely used to study cell growth regulation in cultured cells. We investigated the role of mouse polyomavirus T antigens, small-, middle- and large-T, in stimulating growth-arrested REF52 fibroblasts to enter the S phase. Microinjecting cells with cDNAs encoding the various T antigens showed: first, that middle-T expression blocked cell cycle stimulation by serum; second, that middle-T-arrested cells were released into the S phase upon coexpression of small-T; third, that expression of middle-T together with large-T committed resting cells to enter the cell cycle even in the absence of serum. Our data indicate that extensive cooperation among polyomavirus T antigens is essential for T antigen-mediated cell cycle stimulation in growth-arrested cells. In addition, the data suggest a new role for small-T in signalling to mitogenic pathways.