A novel p53-inducible gene, PAG608, encodes a nuclear zinc finger protein whose overexpression promotes apoptosis
D Israeli1, E Tessler, Y Haupt
1Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel.
Abstract:
The biological effects of the p53 tumor suppressor protein are elicited, at least in part, through sequence-specific transactivation of a battery of target genes. The differential display method was employed towards identifying additional p53 target genes, with emphasis on genes whose induction may contribute to p53-mediated apoptosis. We report here the cloning of a novel p53-inducible gene, designated PAG608. PAG608 transcripts are induced by DNA damage in a p53-dependent manner. PAG608 encodes a nuclear zinc finger protein, which appears to localize preferentially to nucleoli when expressed at moderate levels in transfected cells. Transient overexpression of PAG608 in human tumor-derived cells leads to distinctive changes in nuclear morphology, and can promote apoptosis. Together with additional p53 target genes, PAG608 may therefore play a role in mediating the biological activities of p53.
Insights
Researchers identified PAG608, a novel gene induced by DNA damage in a p53-dependent manner. This p53 target gene encodes a nuclear protein that promotes apoptosis and may mediate p53’s tumor suppressor functions.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- The p53 tumor suppressor protein regulates cellular responses to DNA damage.
- p53 exerts its functions by transactivating specific target genes.
- Identifying novel p53 target genes is crucial for understanding p53-mediated biological effects, including apoptosis.
Purpose of the Study:
- To identify novel p53 target genes involved in p53-mediated apoptosis.
- To characterize a newly discovered p53-inducible gene, PAG608.
Main Methods:
- Differential display method was used to identify novel p53 target genes.
- PAG608 gene expression was analyzed in response to DNA damage.
- PAG608 protein localization and functional effects were assessed in transfected human tumor cells.
Main Results:
- A novel p53-inducible gene, PAG608, was identified.
- PAG608 transcripts are upregulated by DNA damage in a p53-dependent manner.
- PAG608 encodes a nuclear zinc finger protein that localizes to nucleoli and promotes apoptosis upon overexpression.
Conclusions:
- PAG608 is a novel p53 target gene induced by DNA damage.
- PAG608 may contribute to p53-mediated apoptosis and its tumor suppressor activities.
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