Modulation of cell growth, p34cdc2 and cyclin A levels by SV-40 large T antigen.

ABSTRACT

Immortalization of rat lung epithelial cells by either wild-type SV-40 T antigen, a mutant form of T antigen that cannot bind pRb, or a temperature-sensitive T antigen increased by five- to 20-fold the steady state levels of p34cdc2 and cyclin A, positive regulators of progression through the cell cycle. Increased abundance of p34cdc2 was not accompanied by equivalent increases in cdc2 mRNA, indicating that increased expression of p34cdc2 is due, at least partially, to post-transcriptional mechanisms. Levels of p34cdc2 and cyclin A protein in cells immortalized with a temperature-sensitive T antigen remained elevated at the restrictive temperature unless T antigen was reduced to levels significantly below those where proliferation ceased, indicating that these two functions can be dissociated. These results show that SV-40 T antigen can dramatically enhance the expression of certain cell cycle regulatory proteins by mechanisms that are independent of pRb binding and cell growth status.