Mutated Atf4 suppresses c-Ha-ras oncogene transcript levels and cellular transformation in NIH3T3 fibroblasts Academic Article uri icon

Overview

MeSH Major

  • Cell Transformation, Neoplastic
  • Genes, ras
  • Proto-Oncogene Proteins p21(ras)
  • Transcription Factors
  • Transcription, Genetic

abstract

  • A frameshift mutation is present in one allele of the Atf4 gene in genomic DNA from F9 embryonal carcinoma stem cells. The mutation results in the fusion of a short 5' open reading frame to the coding sequence of Atf4, replacing the first 18 N-terminal amino acids with 50 amino acids encoded by the upstream open reading frame. The ability of both normal and mutated Atf4 gene products to influence cell growth was tested using an NIH3T3 cell transformation assay. Overexpression of mutant Atf4 suppresses ras-induced transformation in this assay. In G418r cell lines derived from parallel co-transfections, expression of transfected mutant Atf4 mRNA correlates with a loss of transformed morphology and a reduction in ras mRNA levels. Transient cotransfection assays in NIH3T3 cells demonstrate that wild type Atf4 is able to inhibit transcription directed by the human c-Ha-ras1 promoter and that this effect is increased by the mutation.

publication date

  • November 12, 1996

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1006/bbrc.1996.1702

PubMed ID

  • 8920955

Additional Document Info

start page

  • 586

end page

  • 95

volume

  • 228

number

  • 2