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Updated: Sep 21, 2025
07:20
Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy
Published on: January 31, 2025
676
Dusquetide modulates innate immune response through binding to p62
Yi Zhang1, Christina G Towers2, Upendra K Singh3
1Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA; Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106, USA.
Structure (London, England : 1993)
|May 31, 2022
Summary
Dusquetide interacts with SQSTM1/p62, modulating immune responses by affecting the p62-RIP1 complex. This research clarifies the molecular mechanism of innate defense regulators (IDRs) for potential therapeutic targeting.
Area of Science:
- Immunology
- Cell Biology
- Structural Biology
Background:
- SQSTM1/p62 acts as an autophagic receptor crucial for stress and innate immune responses.
- Previous studies suggested p62 is a target for innate defense regulators (IDRs), but the mechanism was unknown.
Purpose of the Study:
- To elucidate the structural basis and biological effects of dusquetide's interaction with SQSTM1/p62.
- To understand the molecular mechanism of next-generation IDRs targeting p62.
Main Methods:
- Investigated the complex formation between dusquetide and the ZZ domain of p62 using structural and biochemical analyses.
- Assessed dusquetide's cellular uptake and its effects on p62-RIP1 complex, p38 phosphorylation, and CEBP/B expression in vivo.
Main Results:
- Dusquetide binds to the ZZ domain of p62 through electrostatic and hydrophobic interactions.
- Dusquetide enters cells and modulates the p62-RIP1 complex, upregulating p38 phosphorylation and CEBP/B expression without inducing autophagy.
- The study provides detailed molecular insights into dusquetide-p62 interactions.
Conclusions:
- Dusquetide's interaction with p62 provides a molecular mechanism for IDR activity.
- Findings support the development of novel therapeutic strategies targeting p62 for immune modulation.
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