ArticleThe Journal of biological chemistry2009
Role of isoprenylcysteine carboxylmethyltransferase-catalyzed methylation in Rho function and migration.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 48 citations in OpenAlex.
- Targeting ICMT: A promising strategy in cancer treatment (Review).Oncology letters · 2026Review
- The Role of Actin-Binding Proteins in Breast Cancer Progression.Breast cancer (Dove Medical Press) · 2026Review
- Carboxylesterase 1 regulates peroxisome proliferator-activated receptor gamma to inhibit the growth and metastasis of breast cancer cells.Journal of molecular histology · 2025Article
- Protein lipidation in the tumor microenvironment: enzymology, signaling pathways, and therapeutics.Molecular cancer · 2025Review
- RAB4A is a master regulator of cancer cell stemness upstream of NUMB-NOTCH signaling.Cell death & disease · 2024Article
- Folylpolyglutamate synthetase mRNA G-quadruplexes regulate its cell protrusion localization and enhance a cancer cell invasive phenotype upon folate repletion.BMC biology · 2023Article
- RAB4A GTPase regulates epithelial-to-mesenchymal transition by modulating RAC1 activation.Breast cancer research : BCR · 2022Article
- Underappreciated roles for Rho GDP dissociation inhibitors (RhoGDIs) in cell function: Lessons learned from the pancreatic islet β-cell.Biochemical pharmacology · 2022Review
- Isoprenylcysteine carboxyl methyltransferase is critical for glioblastoma growth and survival by activating Ras/Raf/Mek/Erk.Cancer chemotherapy and pharmacology · 2022Article
- Unconventional protein post-translational modifications: the helmsmen in breast cancer.Cell & bioscience · 2022Review
- Effects of isoprenylcysteine carboxylmethyltransferase silencing on the migration and invasion of tongue squamous cell carcinoma.Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2021Article
- Effects of isoprenylcysteine carboxyl methyltransferase silencing on the proliferation and apoptosis of tongue squamous cell carcinoma.Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2021Article
- Post-translational Modifications of the Protein Termini.Frontiers in cell and developmental biology · 2021Review
- Article
- Small change, big effect: Taking RAS by the tail through suppression of post-prenylation carboxylmethylation.Small GTPases · 2020Review
- Beyond the Mevalonate Pathway: Control of Post-Prenylation Processing by Mutant p53.Frontiers in oncology · 2020Review
- Isoprenylcysteine carboxy methyltransferase (ICMT) is associated with tumor aggressiveness and its expression is controlled by the p53 tumor suppressor.The Journal of biological chemistry · 2019Article
- Role of Nicotinamide N-Methyltransferase in Dorsal Striatum in Cocaine Place Preference.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Article
- Article
- Distinct functional relevance of dynamic GTPase cysteine methylation in fission yeast.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 2 countries.
Funding
Abstract
A number of proteins that play key roles in biological regulatory events undergo a process of post-translational modifications termed prenylation. The prenylation pathway consists of three enzymatic steps; the final processed protein is isoprenoid-modified and methylated on the C-terminal cysteine. This protein modification pathway plays a significant role in cancer biology because many oncogenic proteins undergo prenylation. Methylation of the C terminus by isoprenylcysteine carboxylmethyltransferase (Icmt) is the final step in the prenylation pathway. Cysmethynil, a specific Icmt inhibitor discovered in our laboratory, is able to inhibit Ras-mediated signaling, cell growth, and oncogenesis. We sought to examine the role of Icmt-mediated methylation on the behaviors of cancer cells associated with metastatic potential. Our results indicate that inhibition of methylation reduces migration of the highly metastatic MDA-MB-231 breast cancer cell line. In addition, cell adhesion and cell spreading are also significantly impacted by cysmethynil. To examine the mechanism of Icmt-dependent migration we focused on RhoA and Rac1, prenylated proteins that are important mediators of cell migration through their control of the actin cytoskeleton. Inhibition of Icmt significantly decreases the activation of both RhoA and Rac1; an increase in Rho GDP-dissociation inhibitor (RhoGDI) binding in the absence of methylation appears to contribute to this effect. Furthermore, in the absence of Icmt activity the addition of exogenous RhoA or Rac1 is able to partially rescue directed and random migration, respectively. These findings establish a role for Icmt-mediated methylation in cell migration and advance our understanding of the biological consequences of Rho methylation.
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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.