ArticleJournal of the American Chemical Society2022
Adaptor-Specific Antibody Fragment Inhibitors for the Intracellular Modulation of p97 (VCP) Protein-Protein Interactions.
Article in Journal of the American Chemical Society, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- Development of a NanoBRET assay for evaluation of 14-3-3σ molecular glues.SLAS discovery : advancing life sciences R & D · 2024Article
- CytoSIP: an annotated structural atlas for interactions involving cytokines or cytokine receptors.Communications biology · 2024Article
- Golgi defect as a major contributor to lysosomal dysfunction.Frontiers in cell and developmental biology · 2024Review
- Autophagy Receptor-Inspired Antibody-Fusion Proteins for Targeted Intracellular Degradation.Journal of the American Chemical Society · 2023Article
- Structural insights of the p97/VCP AAA+ ATPase: How adapter interactions coordinate diverse cellular functionality.The Journal of biological chemistry · 2023Review
- Valosin containing protein (VCP): initiator, modifier, and potential drug target for neurodegenerative diseases.Molecular neurodegeneration · 2023Review
- Targeting of client proteins to the VCP/p97/Cdc48 unfolding machine.Frontiers in molecular biosciences · 2023Review
- Developing a Novel Immune-Related Seven-Gene Signature and Immune Infiltration Pattern in Patients with COVID-19 and Cardiovascular Disease.Journal of cardiovascular development and disease · 2022Article
- Mechanisms of Sodium/Iodide Symporter-Mediated Mammary Gland Iodine Compensation during Lactation.Nutrients · 2022Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Protein-protein interactions (PPIs) form complex networks to drive cellular signaling and cellular functions. Precise modulation of a target PPI helps explain the role of the PPI in cellular events and possesses therapeutic potential. For example, valosin-containing protein (VCP/p97) is a hub protein that interacts with more than 30 adaptor proteins involved in various cellular functions. However, the role of each p97 PPI during the relevant cellular event is underexplored. The development of small-molecule PPI modulators remains challenging due to a lack of grooves and pockets in the relatively large PPI interface and the fact that a common binding groove in p97 binds to multiple adaptors. Here, we report an antibody fragment-based modulator for the PPI between p97 and its adaptor protein NSFL1C (p47). We engineered these antibody modulators by phage display against the p97-interacting domain of p47 and minimizing binding to other p97 adaptors. The selected antibody fragment modulators specifically disrupt the intracellular p97/p47 interaction. The potential of this antibody platform to develop PPI inhibitors in therapeutic applications was demonstrated through the inhibition of Golgi reassembly, which requires the p97/p47 interaction. This study presents a unique approach to modulate specific intracellular PPIs using engineered antibody fragments, demonstrating a method to dissect the function of a PPI within a convoluted PPI network.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.