title: p53 dependent growth suppression by the c-Abl nuclear tyrosine kinase.
abstract: 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.
authors.affiliation: Molecular Biology Institute, University of California, Los Angeles 90095, USA.
authors.forename: A
authors.initials: A
authors.lastname: Goga
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.forename: T M
authors.initials: TM
authors.lastname: Hambuch
authors.forename: K
authors.initials: K
authors.lastname: Senechal
authors.forename: E
authors.initials: E
authors.lastname: Major
authors.forename: A J
authors.initials: AJ
authors.lastname: Berk
authors.forename: O N
authors.initials: ON
authors.lastname: Witte
authors.forename: C L
authors.initials: CL
authors.lastname: Sawyers
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002455:Cell Division; D002467:Cell Nucleus / Q000201:enzymology*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005347:Fibroblasts; D016161:Genes, Retinoblastoma; D016158:Genes, p53; D051379:Mice; D008817:Mice, Mutant Strains; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000096:biosynthesis / Q000378:metabolism*; D017384:Sequence Deletion; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl