ArticleThe Journal of clinical investigation2004
Inactivation of Icmt inhibits transformation by oncogenic K-Ras and B-Raf.
Article in The Journal of clinical investigation, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 162 citations in OpenAlex.
- ICMT supports BRAFProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Targeting ICMT: A promising strategy in cancer treatment (Review).Oncology letters · 2026Review
- ICMT deficiency ameliorates weight loss and mortality, but not tumor formation in a mouse model of liver cancer.Cell communication and signaling : CCS · 2026Article
- Synthetic essentiality of isoprenylcysteine carboxylmethyltransferase in PTEN deficient triple negative breast cancer.Experimental hematology & oncology · 2026Article
- Uncovering the prevalence, key biogenesis enzymes, and biological significance of archaeal lipoproteins.Nature communications · 2025Article
- Preclinical Evaluation of [ACS pharmacology & translational science · 2024Article
- The Emerging Role of p21 in Diabetes and Related Metabolic Disorders.International journal of molecular sciences · 2024Review
- Targeted genetic and small molecule disruption of N-Ras CaaX cleavage alters its localization and oncogenic potential.Bioorganic chemistry · 2024Article
- KRAS: Biology, Inhibition, and Mechanisms of Inhibitor Resistance.Current oncology (Toronto, Ont.) · 2024Review
- Protein lipidation in cancer: mechanisms, dysregulation and emerging drug targets.Nature reviews. Cancer · 2024Review
- Protein lipidation in health and disease: molecular basis, physiological function and pathological implication.Signal transduction and targeted therapy · 2024Review
- Rho of Plants patterning: linking mathematical models and molecular diversity.Journal of experimental botany · 2024Review
- Article
- Suppression of isoprenylcysteine carboxylmethyltransferase compromises DNA damage repair.Life science alliance · 2021Article
- Post-translational modification of KRAS: potential targets for cancer therapy.Acta pharmacologica Sinica · 2021Review
- Article
- A small-molecule ICMT inhibitor delays senescence of Hutchinson-Gilford progeria syndrome cells.eLife · 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
- Polyisoprenylated Cysteinyl Amide Inhibitors: A Novel Approach to Controlling Cancers with Hyperactive Growth Signaling.Current medicinal chemistry · 2021Article
33 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Isoprenylcysteine carboxyl methyltransferase (Icmt) methylates the carboxyl-terminal isoprenylcysteine of CAAX proteins (e.g., Ras and Rho proteins). In the case of the Ras proteins, carboxyl methylation is important for targeting of the proteins to the plasma membrane. We hypothesized that a knockout of Icmt would reduce the ability of cells to be transformed by K-Ras. Fibroblasts harboring a floxed Icmt allele and expressing activated K-Ras (K-Ras-Icmt(flx/flx)) were treated with Cre-adenovirus, producing K-Ras-Icmt(Delta/Delta) fibroblasts. Inactivation of Icmt inhibited cell growth and K-Ras-induced oncogenic transformation, both in soft agar assays and in a nude mice model. The inactivation of Icmt did not affect growth factor-stimulated phosphorylation of Erk1/2 or Akt1. However, levels of RhoA were greatly reduced as a consequence of accelerated protein turnover. In addition, there was a large Ras/Erk1/2-dependent increase in p21(Cip1), which was probably a consequence of the reduced levels of RhoA. Deletion of p21(Cip1) restored the ability of K-Ras-Icmt(Delta/Delta) fibroblasts to grow in soft agar. The effect of inactivating Icmt was not limited to the inhibition of K-Ras-induced transformation: inactivation of Icmt blocked transformation by an oncogenic form of B-Raf (V599E). These studies identify Icmt as a potential target for reducing the growth of K-Ras- and B-Raf-induced malignancies.
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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.