p53 mutations isolated in yeast based on loss of transcription factor activity: Similarities and differences from p53 mutations detected in human tumors

Charles B. Epstein, Edward F. Attiyeh, David A. Hobson, Abigail L. Silver, James Broach, Arnold J. Levine

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

p53 is a transcriptional activator that plays a key role in the integration of signals inducing cell division arrest and programed cell death. Moreover, p53 is a tumor suppressor gene, mutations of which are the most commonly detected mutations in diverse malignancies. In order to better understand the significance of p53 mutations to human cancer, we isolated mutant alleles of p53 that had lost transcription factor activity in yeast. These mutant alleles were evaluated for their precise changes, their activity against three different p53 responsive enhancers and their ability to act in a transdominant fashion to the wild type allele. While many of the mutations isolated in yeast resembled those found in human tumors, consistent with the importance of transcription factor activity for p53 in mammalian cells, the mutational spectrum obtained was dependent upon the p53 enhancer employed for the selection. Some mutations specifically inactivated p53 in yeast for a single enhancer element. Virtually all missense mutations tested had a dominant inhibitory effect on wild type p53 in yeast. Since some of these transdominant mutations are virtually unknown in human tumors we conclude that transdominance, per se, fails to predict which mutations occur frequently in cancer.

Original languageEnglish (US)
Pages (from-to)2115-2122
Number of pages8
JournalOncogene
Volume16
Issue number16
DOIs
StatePublished - Apr 23 1998

Fingerprint

Transcription Factors
Yeasts
Mutation
Neoplasms
Alleles
Genetic Suppression
Missense Mutation
Tumor Suppressor Genes
Cell Division
Cell Death

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Epstein, Charles B. ; Attiyeh, Edward F. ; Hobson, David A. ; Silver, Abigail L. ; Broach, James ; Levine, Arnold J. / p53 mutations isolated in yeast based on loss of transcription factor activity : Similarities and differences from p53 mutations detected in human tumors. In: Oncogene. 1998 ; Vol. 16, No. 16. pp. 2115-2122.
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p53 mutations isolated in yeast based on loss of transcription factor activity : Similarities and differences from p53 mutations detected in human tumors. / Epstein, Charles B.; Attiyeh, Edward F.; Hobson, David A.; Silver, Abigail L.; Broach, James; Levine, Arnold J.

In: Oncogene, Vol. 16, No. 16, 23.04.1998, p. 2115-2122.

Research output: Contribution to journalArticle

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