P53 DEPENDENT GROWTH SUPPRESSION BY THE C-ABL NUCLEAR TYROSINE KINASE

Growth suppression by the Rb and p53 tumor suppressor proteins is medi ated through effects on cell cycle regulatory proteins at the G1/S tra nsition. Because overexpression of c-Abl induces G1 arrest in fibrobla sts, we reasoned that c-Abl may also affect cell cycle proteins which regulate G1. We used fibroblasts containing disruptions of the Rb or p 53 genes to genetically test the role of these proteins in c-Abl growt h suppression. We find that c-Abl requires p53 but not Rb to suppress growth, c-Abl binds p53 in vitro and enhances p53 dependent transcript ion from a promoter containing p53 DNA binding sites. An Abl mutant wh ich no longer binds p53 does not enhance p53 transcriptional activity and fails to suppress growth. These findings provide a novel link betw een a growth inhibitory tyrosine kinase and the p53 tumor suppressor p rotein.