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USP13 modulates the stability of the APC/C adaptor CDH1
Mara Esposito1,2, Gustavo J Gutierrez3,4
1Laboratory of Pathophysiological Cell Signaling, Department of Biology, Faculty of Science and Bioengineering Sciences, Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussels, Belgium. m.esposito@unibas.ch.
Molecular Biology Reports
|April 10, 2022
Summary
The deubiquitinating enzyme USP13 stabilizes CDH1 levels, revealing a new regulatory axis (USP13-CDH1-Aurora B) essential for cell cycle progression and potentially linked to cancer.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The cell division cycle is tightly regulated by E3 ubiquitin ligases and deubiquitinating enzymes (DUBs).
- USP13, a DUB, was previously shown to regulate Aurora B levels during the cell cycle.
- This prompted an investigation into USP13's potential role in regulating the APC/CCDH1 complex, a key controller of Aurora B.
Purpose of the Study:
- To investigate the interaction between USP13 and CDH1.
- To determine if USP13 influences CDH1 protein levels.
- To elucidate the role of the USP13-CDH1 interaction in cell cycle regulation.
Main Methods:
- Immunoprecipitation and western-blotting were used to assess USP13-CDH1 interaction.
- Gain and loss of function studies were performed using USP13 overexpression and knockdown (siRNA/shRNA).
- Protein levels, including CDH1, were quantified via western-blotting.
Main Results:
- USP13 was found to directly bind to CDH1, an adaptor for the APC/C E3 ubiquitin ligase.
- USP13 was demonstrated to control CDH1 protein levels.
- Overexpression of USP13 led to increased CDH1 levels, while USP13 depletion decreased CDH1 levels.
Conclusions:
- USP13 stabilizes CDH1 protein levels, establishing a novel regulatory interplay.
- The USP13-CDH1-Aurora B axis is identified as a critical module for accurate cell cycle progression in mammals.
- Dysregulation of this axis may contribute to cancer development through altered cell cycle pathways.
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