p53 dependent growth suppression by the c-Abl nuclear tyrosine kinase.
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.
Goga
A
A
Molecular Biology Institute, University of California, Los Angeles 90095, USA.
Liu
X
X
Hambuch
T M
TM
Senechal
K
K
Major
E
E
Berk
A J
AJ
Witte
O N
ON
Sawyers
C L
CL
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*
D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl