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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
DJ-1 restores p53 transcription activity inhibited by Topors/p53BP3
Yumi Shinbo1, Takahiro Taira, Takeshi Niki
1Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Abstract:
DJ-1 is a multi-functional protein that plays roles in transcriptional regulation and anti-oxidative stress, and loss of its function is thought to result in onset of Parkinson's disease. Here, we report that DJ-1 bound to Topors/p53BP3, a ring finger protein binding to both topoisomerase I and p53, in vitro and in vivo and that both proteins were colocalized in cells. DJ-1 and p53 were then found to be sumoylated by Topors in cells. It was also found that DJ-1 bound to p53 in vitro and in vivo and that colocalization with and its binding to p53 were stimulated by UV irradiation of cells. Transcription activity of p53 was found to be abrogated by Topors concomitant with sumoylation of p53 in a dose-dependent manner, and DJ-1 restored its repressed activity by releasing the sumoylated form of p53. These findings suggest that DJ-1 positively regulates p53 through Topors-mediated sumoylation.
Insights
DJ-1 protein interacts with Topors and p53, influencing p53
Area of Science:
- Molecular Biology
- Cell Biology
- Neuroscience
Background:
- DJ-1 is a multifunctional protein implicated in Parkinson's disease pathogenesis.
- DJ-1's roles in transcriptional regulation and oxidative stress response are established.
- Topors (p53BP3) is a ring finger protein interacting with topoisomerase I and p53.
Purpose of the Study:
- To investigate the interaction between DJ-1 and Topors.
- To elucidate the role of DJ-1 in regulating p53 activity.
- To understand the mechanism of DJ-1's influence on p53 sumoylation.
Main Methods:
- In vitro and in vivo binding assays.
- Cellular colocalization studies.
- UV irradiation to stimulate protein interactions.
- Analysis of p53 transcriptional activity and sumoylation levels.
Main Results:
- DJ-1 binds to Topors and p53 both in vitro and in vivo.
- DJ-1 and Topors colocalize within cells.
- Topors mediates sumoylation of DJ-1 and p53.
- UV irradiation enhances DJ-1 and p53 binding and colocalization.
- Topors abrogates p53 transcriptional activity via sumoylation.
- DJ-1 restores repressed p53 activity by releasing sumoylated p53.
Conclusions:
- DJ-1 positively regulates p53 transcriptional activity.
- This regulation occurs through Topors-mediated sumoylation.
- DJ-1's function in p53 regulation may be relevant to Parkinson's disease.
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