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Updated: Jun 10, 2025
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Method for Measuring the Activity of Deubiquitinating Enzymes in Cell Lines and Tissue Samples
Published on: May 10, 2015
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The Deubiquitinating Enzyme USP4 Promotes Trophoblast Dysfunction by Stabilizing RYBP
Xuandi Wu1, Jia Hong2, Liang Hong3
1Department of Obstetrics, Northwest Women's and Children's Hospital, Xi'an, Shaanxi, China.
Cell Biochemistry and Biophysics
|October 15, 2024
Summary
Preeclampsia (PE) involves trophoblast dysfunction. This study found that decreased USP4-mediated ubiquitination increases RYBP, impairing trophoblast function and offering a new therapeutic target for PE.
Area of Science:
- Reproductive Biology
- Molecular Pathogenesis
- Biochemistry
Background:
- Preeclampsia (PE) pathogenesis involves impaired spiral artery remodeling, placental dysfunction, and insufficient trophoblast infiltration.
- Ring 1 and YY1 binding protein (RYBP) is linked to trophoblast dysfunction, but its precise role in PE is unclear.
Purpose of the Study:
- To elucidate the molecular mechanism of RYBP in trophoblasts during preeclampsia (PE).
- To investigate the interaction between RYBP and Ubiquitin-specific peptidase 4 (USP4) in PE pathogenesis.
Main Methods:
- Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot assays were used to measure RYBP, USP4, and PI3K/AKT pathway proteins.
- Cellular assays (MTT, EdU, flow cytometry, Transwell, wound healing) assessed trophoblast function.
- Co-immunoprecipitation (CoIP) verified the USP4-RYBP interaction.
Main Results:
- RYBP and USP4 were upregulated in placental tissues from PE patients.
- RYBP overexpression or USP4 upregulation impaired trophoblast viability, proliferation, invasion, migration, and promoted apoptosis.
- USP4 deubiquitinates and stabilizes RYBP, inhibiting the PI3K/AKT pathway.
Conclusions:
- Decreased USP4-mediated ubiquitination enhances RYBP expression, adversely affecting trophoblast function in PE.
- USP4-RYBP interaction and its regulation of the PI3K/AKT pathway present a novel therapeutic target for preeclampsia.
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