ArticleCell chemical biology2022
Temporal proteomics reveal specific cell cycle oncoprotein downregulation by p97/VCP inhibition.
Article in Cell chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- CRISPR screens identify the ATPase VCP as a druggable therapeutic vulnerability in cholangiocarcinoma.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Harnessing p97/VCP: A Transformative AAA+ ATPase Target for Next-Generation Cancer Therapeutics.Cancers · 2025Review
- Mechanism of allosteric inhibition of human p97/VCP ATPase and its disease mutant by triazole inhibitors.Communications chemistry · 2024Article
- The AAA-ATPase Ter94 regulates wing size in Drosophila by suppressing the Hippo pathway.Communications biology · 2024Article
- Enrichment on steps, not genes, improves inference of differentially expressed pathways.PLoS computational biology · 2024Article
- Proteomics analysis reveals the differential impact of the p97 inhibitor CB-5083 on protein levels in various cellular compartments of the HL-60 cell line.microPublication biology · 2024Article
- Perturbation of endoplasmic reticulum proteostasis triggers tissue injury in the thyroid gland.JCI insight · 2023Article
- Tidyproteomics: an open-source R package and data object for quantitative proteomics post analysis and visualization.BMC bioinformatics · 2023Article
- Discovery of novel benzylquinazoline molecules as p97/VCP inhibitors.Frontiers in pharmacology · 2023Article
- Proteomic characterization of post-translational modifications in drug discovery.Acta pharmacologica Sinica · 2022Review
- Multiple UBX proteins reduce the ubiquitin threshold of the mammalian p97-UFD1-NPL4 unfoldase.eLife · 2022Article
- The Cure VCP Scientific Conference 2021: Molecular and clinical insights into neurodegeneration and myopathy linked to multisystem proteinopathy-1 (MSP-1).Neurobiology of disease · 2022Review
- NMS-873 Leads to Dysfunctional Glycometabolism in A p97-Independent Manner in HCT116 Colon Cancer Cells.Pharmaceutics · 2022Article
- Cdc48 influence on separase levels is independent of mitosis and suggests translational sensitivity of separase.Cell reports · 2022Article
- The p97 Inhibitor UPCDC-30245 Blocks Endo-Lysosomal Degradation.Pharmaceuticals (Basel, Switzerland) · 2022Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Targeting protein quality control (PQC) pathways using proteasome or p97/VCP inhibition can effectively treat blood tumors. However, in solid tumors, only p97/VCP inhibitors are effective. To probe this difference in efficacy, we tracked HCT116 colon cancer cells using temporal proteomics to define the cellular and molecular responses to proteasome and p97 inhibition. Proteins involved in general PQC pathways were similarly upregulated by both treatments, suggesting that the proteotoxic stress caused by inhibitors does not explain the differential therapeutic effectiveness. Unexpectedly, proteins specifically dysregulated by two p97 inhibitors are involved in cell cycle control. Indeed, eleven cell cycle proteins were downregulated by p97 inhibition but not by proteasome inhibition. Western blot analysis validated the degradation of cyclin D1 and Securin, which depends on proteasome but not on p97. Differing regulation of cell cycle proteins by p97 and the proteasome may, therefore, explain the therapeutic efficacy of p97 inhibitors in colon cancer.
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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.