ArticleJournal of cell science2019
Acylpeptide hydrolase is a novel regulator of KRAS plasma membrane localization and function.
Article in Journal of cell science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- MTMR regulates KRAS function by controlling plasma membrane levels of phospholipids.The Journal of cell biology · 2025Article
- A new ferrocene derivative blocks K-Ras localization and function by oxidative modification at His95.Life science alliance · 2023Article
- A carbapenem antibiotic inhibiting a mammalian serine protease: structure of the acylaminoacyl peptidase-meropenem complex.Chemical science · 2022Article
- Differential Distribution and Activity Profile of Acylpeptide Hydrolase in the Rat Seminiferous Epithelium.Biomedicines · 2022Article
- Cryo-EM structure of acylpeptide hydrolase reveals substrate selection by multimerization and a multi-state serine-protease triad.Chemical science · 2022Article
- Approaches to inhibiting oncogenic K-Ras.Small GTPases · 2021Review
- The KRAS and other prenylated polybasic domain membrane anchors recognize phosphatidylserine acyl chain structure.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Blocking K-Ras Interaction With the Plasma Membrane Is a Tractable Therapeutic Approach to Inhibit Oncogenic K-Ras Activity.Frontiers in molecular biosciences · 2021Review
- RAS Function in cancer cells: translating membrane biology and biochemistry into new therapeutics.The Biochemical journal · 2020Review
- Avicin G is a potent sphingomyelinase inhibitor and blocks oncogenic K- and H-Ras signaling.Scientific reports · 2020Article
- Precise and efficient silencing of mutant KrasTheranostics · 2020Article
- RAS: Striking at the Core of the Oncogenic Circuitry.Frontiers in oncology · 2019Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The primary site for KRAS signaling is the inner leaflet of the plasma membrane (PM). We previously reported that oxanthroquinone G01 (G01) inhibited KRAS PM localization and blocked KRAS signaling. In this study, we identified acylpeptide hydrolase (APEH) as a molecular target of G01. APEH formed a stable complex with biotinylated G01, and the enzymatic activity of APEH was inhibited by G01. APEH knockdown caused profound mislocalization of KRAS and reduced clustering of KRAS that remained PM localized. APEH knockdown also disrupted the PM localization of phosphatidylserine (PtdSer), a lipid critical for KRAS PM binding and clustering. The mislocalization of KRAS was fully rescued by ectopic expression of APEH in knockdown cells. APEH knockdown disrupted the endocytic recycling of epidermal growth factor receptor and transferrin receptor, suggesting that abrogation of recycling endosome function was mechanistically linked to the loss of KRAS and PtdSer from the PM. APEH knockdown abrogated RAS-RAF-MAPK signaling in cells expressing the constitutively active (oncogenic) mutant of KRAS (KRASG12V), and selectively inhibited the proliferation of KRAS-transformed pancreatic cancer cells. Taken together, these results identify APEH as a novel drug target for a potential anti-KRAS therapeutic.
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Registered trials
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