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Visualization of Protein-protein Interaction in Nuclear and Cytoplasmic Fractions by Co-immunoprecipitation and In Situ Proximity Ligation Assay
Published on: January 16, 2017
USP7 at PML Nuclear Bodies: A Protein Interaction Network Perspective.
Sergey A Silonov1, Ekaterina S Vedeshkina1, Yakov I Mokin1
1The Biomolecular Condensates and Membraneless Organelles Group, Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Ave., 194064 St. Petersburg, Russia.
Ubiquitin-specific protease 7 (USP7) interacts with PML nuclear bodies (PML-NBs), revealing shared roles in gene regulation and DNA repair. This study uncovers a novel cellular network linking USP7, PML-NBs, aging, and senescence.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Ubiquitin-specific protease 7 (USP7) is a key deubiquitinating enzyme regulating cellular processes and is a therapeutic target.
- USP7 partially localizes with PML nuclear bodies (PML-NBs), complex organelles involved in post-translational modifications, but their association is uncharacterized.
Purpose of the Study:
- To investigate the molecular basis and functional significance of USP7's association with PML-NBs.
- To identify shared proteins and functional contexts between USP7 and PML-NBs.
Main Methods:
- Comparative interactome analysis of USP7 and PML.
- Functional enrichment analysis using bioinformatics tools.
- Network analysis of overlapping proteins with core PML-NB components.
Main Results:
- A significant overlap of 166 proteins was identified between USP7 and PML interactomes.
- Shared proteins are involved in transcriptional regulation, chromatin remodeling, DNA damage response, cellular senescence, and aging.
- A dense network of 61 overlapping proteins with core PML-NB components was identified, characterized by liquid-liquid phase separation and intrinsic disorder.
Conclusions:
- USP7 and PML-NBs operate within a common molecular context relevant to aging and senescence.
- PML-NBs provide a crucial cellular environment for understanding USP7's functions and regulation.
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