p53 dependent growth suppression by the c-Abl nuclear tyrosine kinase

Oncogene. 1995 Aug 17;11(4):791-9.


Growth suppression by the Rb and p53 tumor suppressor proteins is mediated through effects on cell cycle regulatory proteins at the G1/S transition. Because overexpression of c-Abl induces G1 arrest in fibroblasts, we reasoned that c-Abl may also affect cell cycle proteins which regulate G1. We used fibroblasts containing disruptions of the Rb or p53 genes to genetically test the role of these proteins in c-Abl growth suppression. We find that c-Abl requires p53 but not Rb to suppress growth. c-Abl binds p53 in vitro and enhances p53 dependent transcription from a promoter containing p53 DNA binding sites. An Abl mutant which no longer binds p53 does not enhance p53 transcriptional activity and fails to suppress growth. These findings provide a novel link between a growth inhibitory tyrosine kinase and the p53 tumor suppressor protein.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Cycle*
  • Cell Division*
  • Cell Nucleus / enzymology*
  • Cells, Cultured
  • Embryo, Mammalian
  • Fibroblasts
  • Genes, Retinoblastoma
  • Genes, p53
  • Mice
  • Mice, Mutant Strains
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins c-abl / metabolism*
  • Retinoblastoma Protein / biosynthesis
  • Retinoblastoma Protein / metabolism*
  • Sequence Deletion
  • Transcription, Genetic
  • Transcriptional Activation*
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tumor Suppressor Protein p53 / metabolism*


  • Retinoblastoma Protein
  • Tumor Suppressor Protein p53
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-abl