ArticleBioorganic & medicinal chemistry2016
8-Hydroxyquinoline-based inhibitors of the Rce1 protease disrupt Ras membrane localization in human cells.
Article in Bioorganic & medicinal chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 67 citations in OpenAlex.
- Lawsonia intracellularis T3SS effector LI0758, an Rce1 ortholog, activates MAPK and NF-κB signaling in mammalian cells.Veterinary research · 2025Article
- Targeting MDM2, RAS, and PCNA for cancer targeted therapy: pan-cancer approaches vs. cancer-specific strategies.Frontiers in pharmacology · 2025Review
- An overview of recent advancements in small molecules suppression of oncogenic signaling of K-RAS: an updated review.Molecular diversity · 2024Review
- Targeted genetic and small molecule disruption of N-Ras CaaX cleavage alters its localization and oncogenic potential.Bioorganic chemistry · 2024Article
- Evaluating protein prenylation of human and viral CaaX sequences using a humanized yeast system.Disease models & mechanisms · 2024Article
- Protein lipidation in health and disease: molecular basis, physiological function and pathological implication.Signal transduction and targeted therapy · 2024Review
- A Humanized Yeast System for Evaluating the Protein Prenylation of a Wide Range of Human and Viral CaaX Sequences.bioRxiv : the preprint server for biology · 2023Article
- Synthesis of Bioactive Aminomethylated 8-Hydroxyquinolines via the Modified Mannich Reaction.International journal of molecular sciences · 2023Review
- Protein Prenyltransferases and Their Inhibitors: Structural and Functional Characterization.International journal of molecular sciences · 2022Review
- Small-Molecule MMRi62 Induces Ferroptosis and Inhibits Metastasis in Pancreatic Cancer via Degradation of Ferritin Heavy Chain and Mutant p53.Molecular cancer therapeutics · 2022Article
- Post-translational modification of KRAS: potential targets for cancer therapy.Acta pharmacologica Sinica · 2021Review
- Review
- A Novel KRAS Antibody Highlights a Regulation Mechanism of Post-Translational Modifications of KRAS during Tumorigenesis.International journal of molecular sciences · 2020Article
- RAS-targeted therapies: is the undruggable drugged?Nature reviews. Drug discovery · 2020Review
- Small change, big effect: Taking RAS by the tail through suppression of post-prenylation carboxylmethylation.Small GTPases · 2020Review
- KRAS G12C Game of Thrones, which direct KRAS inhibitor will claim the iron throne?Cancer treatment reviews · 2020Review
- Biology, pathology, and therapeutic targeting of RAS.Advances in cancer research · 2020Review
- RCE1 deficiency enhances invasion via the promotion of epithelial-mesenchymal transition and predicts poor prognosis in hepatocellular carcinoma.American journal of translational research · 2020Article
- Breaking the Fourth Wall: Modulating Quaternary Associations for Protein Regulation and Drug Discovery.Chembiochem : a European journal of chemical biology · 2019Review
- [Effects of silencing Rce1 in vitro on the invasion and migration of tongue carcinoma].Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2019Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Ras converting enzyme 1 (Rce1) is an endoprotease that catalyzes processing of the C-terminus of Ras protein by removing -aaX from the CaaX motif. The activity of Rce1 is crucial for proper localization of Ras to the plasma membrane where it functions. Ras is responsible for transmitting signals related to cell proliferation, cell cycle progression, and apoptosis. The disregulation of these pathways due to constitutively active oncogenic Ras can ultimately lead to cancer. Ras, its effectors and regulators, and the enzymes that are involved in its maturation process are all targets for anti-cancer therapeutics. Key enzymes required for Ras maturation and localization are the farnesyltransferase (FTase), Rce1, and isoprenylcysteine carboxyl methyltransferase (ICMT). Among these proteins, the physiological role of Rce1 in regulating Ras and other CaaX proteins has not been fully explored. Small-molecule inhibitors of Rce1 could be useful as chemical biology tools to understand further the downstream impact of Rce1 on Ras function and serve as potential leads for cancer therapeutics. Structure-activity relationship (SAR) analysis of a previously reported Rce1 inhibitor, NSC1011, has been performed to generate a new library of Rce1 inhibitors. The new inhibitors caused a reduction in Rce1 in vitro activity, exhibited low cell toxicity, and induced mislocalization of EGFP-Ras from the plasma membrane in human colon carcinoma cells giving rise to a phenotype similar to that observed with siRNA knockdowns of Rce1 expression. Several of the new inhibitors were more effective at mislocalizing K-Ras compared to a potent farnesyltransferase inhibitor (FTI), which is significant because of the preponderance of K-Ras mutations in cancer.
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