P53

A transdominant regulator of transcription whose function is ablated by mutations occurring in human cancer

Tamar Unger, Marion M. Nau, Shoshana Segal, John D. Minna

Research output: Contribution to journalArticle

217 Citations (Scopus)

Abstract

Gal4-p53 fusion constructs demonstrate that wild type p53 is a potent transactivator in human lung cancer cells with the transactivation domain for p53 residing in amino acids 1-42. Strikingly, a variety of lung cancer derived p53 mutations occurring outside this domain disrupt this activity. Temperature sensitive conformational shifts of p53 mutant proteins to the wild type form exist and, with a temperature downshift, several mutants become transcriptionally active. Wild type p53 protein is known to form oligomers with mutant p53 and cotransfection of wild type and mutant genes shows that p53 acts in a transdominant manner that is independent of the DNA binding specificity. Transcription is either increased or decreased depending on whether the wild type is more or less abundant than the mutant form. Finally, lung cancers differ in their ability to support the transactivation related functions, providing evidence of other abnormalities of the p53 system in human cancer.

Original languageEnglish (US)
Pages (from-to)1383-1390
Number of pages8
JournalEMBO Journal
Volume11
Issue number4
StatePublished - 1992

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Transcription
Lung Neoplasms
Mutation
Transcriptional Activation
Trans-Activators
Mutant Proteins
Oligomers
Neoplasms
Temperature
Fusion reactions
Genes
p53 Genes
Cells
Amino Acids
DNA
Proteins

Keywords

  • Activation domain
  • Lung cancer
  • P53
  • Temperature sensitivity
  • Transactivation activity

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

P53 : A transdominant regulator of transcription whose function is ablated by mutations occurring in human cancer. / Unger, Tamar; Nau, Marion M.; Segal, Shoshana; Minna, John D.

In: EMBO Journal, Vol. 11, No. 4, 1992, p. 1383-1390.

Research output: Contribution to journalArticle

Unger, Tamar ; Nau, Marion M. ; Segal, Shoshana ; Minna, John D. / P53 : A transdominant regulator of transcription whose function is ablated by mutations occurring in human cancer. In: EMBO Journal. 1992 ; Vol. 11, No. 4. pp. 1383-1390.
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