A mutation in a thioredoxin reductase homolog suppresses p53-induced growth inhibition in the fission yeast Schizosaccharomyces pombe

Casso, D., Beach, D. (October 1996) A mutation in a thioredoxin reductase homolog suppresses p53-induced growth inhibition in the fission yeast Schizosaccharomyces pombe. Mol Gen Genet, 252 (5). pp. 518-29. ISSN 0026-8925 (Print)

URL: http://www.ncbi.nlm.nih.gov/pubmed/8914513
DOI: 10.1007/BF02172398

Abstract

A strong growth inhibition is observed when the human p53 tumor suppressor gene product is expressed in the fission yeast Schizosaccharomyces pombe. This growth inhibition is specific for wild-type p53; mutant alleles of p53 derived from human tumors show a greatly decreased ability to inhibit growth. These data suggest that there may be a p53-responsive pathway in S. pombe. To identify elements in this pathway genetically, we isolated a mutant yeast strain in which the growth inhibitory activity of p53 is largely suppressed. In addition, the activity of p53 as a transcription factor is also decreased in this strain. The suppression of p53 activity is not due to a decrease in p53 expression or a failure of p53 to localize to the nucleus. This p53 suppressor mutation is in a novel S. pombe gene with homology to thioredoxin reductase genes, and has been named trr1. Strains with a mutation of, or deletion in, trr1 are sensitive to oxidizing agents, suggesting that the trr1 suppressor mutation causes partial loss of trr1 function. Since oxidizing agents are able to suppress p53 activity in vitro, this trr1 mutation may affect the activity of p53 in fission yeast by increasing the oxidation state of the tumor suppressor.

Item Type: Paper
Uncontrolled Keywords: Cell Division/genetics Cloning, Molecular Gene Expression Regulation, Fungal Genes, Suppressor Genes, p53 Humans Hydrogen Peroxide/pharmacology Molecular Sequence Data Mutation Oxygen/metabolism/pharmacology Recombinant Proteins/biosynthesis/genetics Research Support, U.S. Gov't, P.H.S. Schizosaccharomyces/drug effects/ genetics/ growth & development Sequence Homology, Amino Acid Thioredoxin Reductase (NADPH)/drug effects/ genetics/metabolism Transcription Factors Tumor Suppressor Protein p53/biosynthesis/genetics
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mutations
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > p53
organism description > yeast
CSHL Authors:
Communities: CSHL labs > Beach lab
Depositing User: Matt Covey
Date: 16 October 1996
Date Deposited: 22 May 2014 15:38
Last Modified: 22 May 2014 15:38
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30168

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