ArticleMolecular and cellular biology1999
Cell growth inhibition by farnesyltransferase inhibitors is mediated by gain of geranylgeranylated RhoB.
Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 250 citations in OpenAlex.
- A phase I study of the farnesyltransferase inhibitor Tipifarnib in combination with the epidermal growth factor tyrosine kinase inhibitor Erlotinib in patients with advanced solid tumors.Investigational new drugs · 2019Trial
- Immunomodulatory effects of atorvastatin on peripheral blood mononuclear cells infected withFrontiers in immunology · 2025Article
- RhoA-ROCK2 signaling possesses complex pathophysiological functions in cancer progression and shows promising therapeutic potential.Cancer cell international · 2024Review
- Mutant HRas Signaling and Rationale for Use of Farnesyltransferase Inhibitors in Head and Neck Squamous Cell Carcinoma.Targeted oncology · 2023Review
- Characterization of Prenylated C-terminal Peptides Using a Thiopropyl-based Capture Technique and LC-MS/MS.Molecular & cellular proteomics : MCP · 2020Article
- FBXW7 regulates endothelial barrier function by suppression of the cholesterol synthesis pathway and prenylation of RhoB.Molecular biology of the cell · 2019Article
- RHO GTPases in cancer: known facts, open questions, and therapeutic challenges.Biochemical Society transactions · 2018Review
- RhoB: Team Oncogene or Team Tumor Suppressor?Genes · 2018Review
- Tipifarnib prevents development of hypoxia-induced pulmonary hypertension.Cardiovascular research · 2017Article
- The p53 isoform delta133p53ß regulates cancer cell apoptosis in a RhoB-dependent manner.PloS one · 2017Article
- Article
- Protein prenylation: unique fats make their mark on biology.Nature reviews. Molecular cell biology · 2016Review
- Critical functions of RhoB in support of glioblastoma tumorigenesis.Neuro-oncology · 2015Article
- Protein prenylation and synaptic plasticity: implications for Alzheimer's disease.Molecular neurobiology · 2014Review
- Modulation of anthracycline-induced cytotoxicity by targeting the prenylated proteome in myeloid leukemia cells.Journal of molecular medicine (Berlin, Germany) · 2012Article
- Measurement of protein farnesylation and geranylgeranylation in vitro, in cultured cells and in biopsies, and the effects of prenyl transferase inhibitors.Nature protocols · 2011Article
- Targeting protein prenylation for cancer therapy.Nature reviews. Cancer · 2011Article
- (--)-Xanthatin selectively induces GADD45γ and stimulates caspase-independent cell death in human breast cancer MDA-MB-231 cells.Chemical research in toxicology · 2011Article
- Breast cancer stem cells survive periods of farnesyl-transferase inhibitor-induced dormancy by undergoing autophagy.Bone marrow research · 2011Article
- 5q- myelodysplastic syndromes: chromosome 5q genes direct a tumor-suppression network sensing actin dynamics.Oncogene · 2009Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Recent results have shown that the ability of farnesyltransferase inhibitors (FTIs) to inhibit malignant cell transformation and Ras prenylation can be separated. We proposed previously that farnesylated Rho proteins are important targets for alternation by FTIs, based on studies of RhoB (the FTI-Rho hypothesis). Cells treated with FTIs exhibit a loss of farnesylated RhoB but a gain of geranylgeranylated RhoB (RhoB-GG), which is associated with loss of growth-promoting activity. In this study, we tested whether the gain of RhoB-GG elicited by FTI treatment was sufficient to mediate FTI-induced cell growth inhibition. In support of this hypothesis, when expressed in Ras-transformed cells RhoB-GG induced phenotypic reversion, cell growth inhibition, and activation of the cell cycle kinase inhibitor p21WAF1. RhoB-GG did not affect the phenotype or growth of normal cells. These effects were similar to FTI treatment insofar as they were all induced in transformed cells but not in normal cells. RhoB-GG did not promote anoikis of Ras-transformed cells, implying that this response to FTIs involves loss-of-function effects. Our findings corroborate the FTI-Rho hypothesis and demonstrate that gain-of-function effects on Rho are part of the drug mechanism. Gain of RhoB-GG may explain how FTIs inhibit the growth of human tumor cells that lack Ras mutations.
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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.