Deletion of the Saccharomyces cerevisiae TRR1 gene encoding thioredoxin reductase inhibits p53-dependent reporter gene expression.
The prevalence of p53 gene mutations in many human tumors implies that p53 protein plays an important role in preventing cancers. Central among the activities ascribed to p53 is its ability to stimulate transcription of other genes that inhibit cells from entering S phase with damaged DNA. Human p53 can be studied in yeast where genetic tools can be used to identify proteins that affect its ability to stimulate transcription. Although p53 strongly stimulated reporter gene expression in wild type yeast, it only weakly stimulated reporter gene expression in Deltatrr1 yeast that lacked the gene encoding thioredoxin reductase. Furthermore, ectoptic expression of TRR1 in Deltatrr1 yeast restored p53-dependent reporter gene activity to high levels. Immunoblot assays established that the Deltatrr1 mutation affected the activity and not the level of p53 protein. The results suggest that p53 can form disulfides and that these disulfides must be reduced in order for the protein to function as a transcription factor.
Pearson
G D
GD
Department of Biochemistry and Biophysics and the Center for Gene Research and Biotechnology, Oregon State University, Corvallis, Oregon 97331, USA.
Merrill
G F
GF
D004268:DNA-Binding Proteins / Q000737:chemistry*; D004220:Disulfides / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal / Q000235:genetics*; D005800:Genes, Fungal / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D013880:Thioredoxin-Disulfide Reductase / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000502:physiology*
D004268:DNA-Binding Proteins; D004220:Disulfides; D005656:Fungal Proteins; D016159:Tumor Suppressor Protein p53; D013880:Thioredoxin-Disulfide Reductase