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Published on: September 10, 2017
p53RDL1 regulates p53-dependent apoptosis
Chizu Tanikawa1, Koichi Matsuda, Seisuke Fukuda
1Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Abstract:
Although a number of targets for p53 have been reported, the mechanism of p53-dependent apoptosis still remains to be elucidated. Here we report a new p53 target-gene, designated p53RDL1 (p53-regulated receptor for death and life; also termed UNC5B). The p53RDL1 gene product contains a cytoplasmic carboxy-terminal death domain that is highly homologous to rat Unc5H2, a dependence receptor involved in the regulation of apoptosis, as well as in axon guidance and migration of neural cells. We found that p53RDL1 mediated p53-dependent apoptosis. Conversely, when p53RDL1 interacted with its ligand, Netrin-1, p53-dependent apoptosis was blocked. Therefore, p53RDL1 seems to be a previously un-recognized target of p53 that may define a new pathway for p53-dependent apoptosis. We suggest that p53 might regulate the survival of damaged cells by balancing the regulation of Netrin-p53RDL1 signalling, and cell death through cleavage of p53RDL1 for apoptosis.
Insights
Researchers identified a new p53 target gene, p53RDL1 (p53-regulated receptor for death and life), which mediates p53-dependent apoptosis. Its interaction with Netrin-1 blocks this cell death pathway, suggesting a novel mechanism for regulating cell survival.
Area of Science:
- Molecular Biology
- Cell Biology
- Neuroscience
Background:
- The precise mechanisms governing p53-dependent apoptosis remain incompletely understood despite numerous identified p53 targets.
- p53 is a critical tumor suppressor protein involved in cellular responses to stress, including apoptosis.
Purpose of the Study:
- To identify and characterize novel p53 target genes involved in the regulation of apoptosis.
- To elucidate a new molecular pathway for p53-mediated cell death.
Main Methods:
- Gene expression analysis to identify p53 target genes.
- Apoptosis assays to assess the role of p53RDL1 in cell death.
- Co-immunoprecipitation to study protein interactions between p53RDL1 and Netrin-1.
Main Results:
- A novel p53 target gene, p53RDL1 (p53-regulated receptor for death and life), also known as UNC5B, was identified.
- p53RDL1 mediates p53-dependent apoptosis.
- Binding of Netrin-1 to p53RDL1 inhibits p53-dependent apoptosis, indicating a regulatory role for Netrin-1.
Conclusions:
- p53RDL1 represents a previously unrecognized target of p53, potentially defining a new pathway for p53-dependent apoptosis.
- p53 may control the survival of damaged cells by modulating Netrin-1/p53RDL1 signaling.
- Cleavage of p53RDL1 could be a critical step in initiating apoptosis, offering a new perspective on p53's role in cell fate decisions.
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