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PMID: 8914513 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

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

Molecular & general genetics : MGG ·Vol. 252 ·No. 5 ·1996-10-16 ·Pages 518-29

Casso D, Beach D

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.

MeSH Terms
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 Schizosaccharomyces/drug effects,genetics,growth & development Sequence Homology, Amino Acid Thioredoxin-Disulfide Reductase/drug effects,genetics,metabolism Transcription Factors Tumor Suppressor Protein p53/biosynthesis,genetics
Chemicals
Recombinant Proteins Transcription Factors Tumor Suppressor Protein p53 Hydrogen Peroxide Thioredoxin-Disulfide Reductase Oxygen
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Casso D
Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, NY 11724, USA.
Beach D
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Article Info
Journal
Molecular & general genetics : MGG
Abbr.
Mol Gen Genet
ISSN
0026-8925
DOI
10.1007/BF02172398
Published
1996-10-16
Pages
518-29
Language
English
Region
Germany
NLM ID
0125036
Subset
IM
Grants
NIGMS NIH HHS · GM39620-08 · United States
Databases
GENBANK
U63713
External Links
PubMed source DOI: 10.1007/BF02172398
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