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Plk1 phosphorylation of Topors is involved in its degradation
Xiaoming Yang1, Hongchang Li, Anping Deng
1College of Chemistry, Sichuan University, Chengdu 610064, China. xiaoming4444@gmail.com
Abstract:
Topors is a DNA topoisomerase I- and p53-binding protein, and mainly functions as a p53 regulator. Accumulating evidence also supports the notion that Topors plays the role as a negative regulator of cell growth, and possibly as a tumor suppressor. Here, we demonstrated that Topors is also involved in normal mitotic progression, since Topors depletion delays mitotic entry and affects mitotic progression. Furthermore, Topors is degradated in response to the activation of the spindle checkpoint. Significantly, Polo-like kinase 1 (Plk1)-associated phosphorylation of Topors at S718 is essential for nocodazole-induced degradation of Topors.
Insights
Topors protein regulates cell growth and tumor suppression. New findings show Topors is crucial for normal mitosis and is degraded when the spindle checkpoint is active, a process regulated by Plk1 phosphorylation.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Topors is a DNA topoisomerase I- and p53-binding protein, primarily acting as a p53 regulator.
- Evidence suggests Topors negatively regulates cell growth and may function as a tumor suppressor.
Purpose of the Study:
- To investigate the role of Topors in mitotic progression.
- To elucidate the mechanism of Topors degradation during mitosis.
Main Methods:
- Depletion of Topors using RNA interference.
- Activation of the spindle assembly checkpoint using nocodazole.
- Analysis of Topors phosphorylation and degradation.
Main Results:
- Topors depletion delays mitotic entry and disrupts mitotic progression.
- Topors undergoes degradation upon activation of the spindle checkpoint.
- Phosphorylation of Topors at serine 718 by Polo-like kinase 1 (Plk1) is critical for its degradation.
Conclusions:
- Topors plays a significant role in normal mitotic progression.
- Topors degradation is a regulated process dependent on spindle checkpoint activation and Plk1-mediated phosphorylation.
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