A COMPLEX BETWEEN E2F AND THE PRB-RELATED PROTEIN P130 IS SPECIFICALLY TARGETED BY THE SIMIAN-VIRUS-40 LARGE T-ANTIGEN DURING CELL-TRANSFORMATION

The p130 protein is a recently cloned member of the retinoblastoma pro tein family. We show here that transformation of NIH3T3-L1 fibroblasts (L1 cells) by the simian virus 40 large T antigen (LTAg) depends on t he disruption of DNA binding complexes between transcription factor E2 F and p130. LTAg binds to the pocket region of p130 in vivo and disrup ts the E2F-p130 complexes. E2F-p130 complexes are present only in quie scent L1 cells and disappear at the G1/S phase boundary concomitantly to induction of DNA synthesis and expression of the E2F-regulated cdc2 gene. p130 is a substrate of cyclin-dependent kinase 2 (Cdk2) in vitr o and associates with a Cdk in vivo which is activated upon serum stim ulation in late G1. Overexpression of p130 inhibits cdc2 promoter acti vity and entry of quiescent L1 cells into S phase. The results demonst rate that p130 is a negative regulator of cell cycle progression which is specifically targeted by LTAg during cell transformation.