Suppression of oncogene-induced transformation by a deletion mutant of c-jun

P. H. Brown, R. Alani, L. H. Preis, E. Szabo, M. J. Birrer

Research output: Contribution to journalArticle

Abstract

Jun and Fos proteins are DNA-binding proteins that are involved in the control of gene expression through transcriptional regulation. We have made a deletion mutant of the c-jun gene that lacks amino acids 3-122 of c-jun, and thus is missing the major transactivation domain of c-jun, but retains the DNA-binding and leucine zipper domains. Unlike c-Jun, the mutant protein is unable to stimulate the transcription of an AP-1 responsive gene, and unlike c-jun this mutant gene is unable to transform rat embryo cells in cooperation with an activated ras gene. However, this mutant protein blocks in vitro DNA binding of Jun-Jun homodimers and Jun-Fos heterodimers, transcriptional activation induced by c-jun or c-fos and transformation of rat embryo cells induced by an activated ras gene and a deregulated c-jun or c-fos gene. In addition, transformation of rat embryo cells induced by an activated ras gene in the presence of the tumor promoter 12-O-tetradecanoyl phorbol 13-acetate (TPA) or by ras plus SV40 large T antigen is also inhibited by this dominant-negative mutant, suggesting that a member of the jun or fos family is involved in the pathways leading to transformation in these systems as well. The possible molecular mechanisms by which this dominant-negative mutant of c-jun blocks the functions of wild-type jun and fos family members are discussed.

Original languageEnglish (US)
Pages (from-to)877-886
Number of pages10
JournalOncogene
Volume8
Issue number4
StatePublished - Apr 1993
Externally publishedYes

Fingerprint

ras Genes
Oncogenes
jun Genes
Embryonic Structures
Mutant Proteins
Transcriptional Activation
Polyomavirus Transforming Antigens
fos Genes
Leucine Zippers
Viral Tumor Antigens
DNA
Transcription Factor AP-1
DNA-Binding Proteins
Tetradecanoylphorbol Acetate
Carcinogens
Gene Expression
Amino Acids
Genes
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

Brown, P. H., Alani, R., Preis, L. H., Szabo, E., & Birrer, M. J. (1993). Suppression of oncogene-induced transformation by a deletion mutant of c-jun. Oncogene, 8(4), 877-886.

Suppression of oncogene-induced transformation by a deletion mutant of c-jun. / Brown, P. H.; Alani, R.; Preis, L. H.; Szabo, E.; Birrer, M. J.

In: Oncogene, Vol. 8, No. 4, 04.1993, p. 877-886.

Research output: Contribution to journalArticle

Brown, PH, Alani, R, Preis, LH, Szabo, E & Birrer, MJ 1993, 'Suppression of oncogene-induced transformation by a deletion mutant of c-jun', Oncogene, vol. 8, no. 4, pp. 877-886.
Brown PH, Alani R, Preis LH, Szabo E, Birrer MJ. Suppression of oncogene-induced transformation by a deletion mutant of c-jun. Oncogene. 1993 Apr;8(4):877-886.
Brown, P. H. ; Alani, R. ; Preis, L. H. ; Szabo, E. ; Birrer, M. J. / Suppression of oncogene-induced transformation by a deletion mutant of c-jun. In: Oncogene. 1993 ; Vol. 8, No. 4. pp. 877-886.
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