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Wig-1, a new p53-induced gene encoding a zinc finger protein
S Varmeh-Ziaie1, I Okan, Y Wang
1Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
Abstract:
Wild type p53 expressed from a temperature-sensitive (ts p53) construct induces both G1 cell cycle arrest and apoptosis in the p53-negative J3D mouse T lymphoma line (Wang et al., 1995). Using differential display analysis, we have identified one new p53-induced gene, wig-1 (for wild type p53-induced gene 1), whose 7.6 kb and 2.2 kb transcripts are upregulated in ts p53-transfected J3D cells following induction of wild type p53 expression by temperature shift to 32 degrees C. The wig-1 transcripts were also induced in irradiated NIH3T3 and p21-/- fibroblasts but not in irradiated p53-/- fibroblasts. Whole body gamma irradiation caused induction of both wig-1 transcripts in mouse brain, testis, kidney, spleen and lung. A basal wig-1 expression was detected in brain, testis and kidney. The WIG-1 protein contains three zinc finger motifs and a putative nuclear localization signal.
Insights
Researchers identified a new gene, wig-1, activated by wild type p53. Wig-1 gene expression increases in response to p53 and DNA damage across various mouse tissues.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- Wild type p53 protein is a crucial tumor suppressor that regulates cell cycle arrest and apoptosis.
- The p53-negative J3D mouse T lymphoma line is a model for studying p53 function.
- Understanding p53-inducible genes is vital for cancer research.
Purpose of the Study:
- To identify novel genes regulated by wild type p53.
- To characterize the expression patterns of a newly identified p53-induced gene, wig-1.
- To investigate the role of wig-1 in response to DNA damage.
Main Methods:
- Differential display analysis was used to identify p53-induced genes.
- Quantitative analysis of wig-1 transcript levels in cell lines and mouse tissues.
- Gamma irradiation was employed to induce DNA damage.
Main Results:
- A novel p53-induced gene, wig-1, was identified with 7.6 kb and 2.2 kb transcripts.
- Wig-1 transcripts were upregulated in p53-transfected cells upon wild type p53 induction.
- Wig-1 induction was observed in irradiated fibroblasts with functional p53 but not in p53-deficient cells.
- Wig-1 transcripts were induced in multiple mouse organs following gamma irradiation.
Conclusions:
- Wig-1 is a novel gene transcriptionally regulated by wild type p53.
- Wig-1 expression is induced by DNA damage in a p53-dependent manner.
- The WIG-1 protein possesses structural features, including zinc finger motifs, suggesting potential DNA-binding activity.