ArticleThe Journal of biological chemistry2013
Efficient use of exogenous isoprenols for protein isoprenylation by MDA-MB-231 cells is regulated independently of the mevalonate pathway.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Prenols and prenoic acids in metabolism, disease, and aging.Journal of lipid research · 2026Review
- Uncovering protein prenylation in Th1 cells: novel prenylation sites and insights into statin and farnesyltransferase inhibition.BMC biology · 2025Article
- An Alkyne-Containing Isoprenoid Analogue Based on a Farnesyl Diphosphate Scaffold Is a Biologically Functional Universal Probe for Proteomic Analysis.Biochemistry · 2025Article
- Beyond the Mevalonate Pathway: Control of Post-Prenylation Processing by Mutant p53.Frontiers in oncology · 2020Review
- Protein Lipidation: Occurrence, Mechanisms, Biological Functions, and Enabling Technologies.Chemical reviews · 2018Article
- FOXF2 differentially regulates expression of metabolic genes in non-cancerous and cancerous breast epithelial cells.Trends in diabetes and metabolism · 2018Article
- Biotransformation of menadione to its prenylated derivative MK-3 using recombinant Pichia pastoris.Journal of industrial microbiology & biotechnology · 2017Article
- Mevalonate Metabolism in Immuno-Oncology.Frontiers in immunology · 2017Review
- Metabolic Labeling with an Alkyne-modified Isoprenoid Analog Facilitates Imaging and Quantification of the Prenylome in Cells.ACS chemical biology · 2016Article
- Article
- Steroid binding to Autotaxin links bile salts and lysophosphatidic acid signalling.Nature communications · 2016Article
- Geranylgeranylation signals to the Hippo pathway for breast cancer cell proliferation and migration.Oncogene · 2015Article
- Global profiling of protein lipidation using chemical proteomic technologies.Current opinion in chemical biology · 2015Review
- Inhibiting geranylgeranylation increases neurite branching and differentially activates cofilin in cell bodies and growth cones.Molecular neurobiology · 2014Article
- Use of synthetic isoprenoids to target protein prenylation and Rho GTPases in breast cancer invasion.PloS one · 2014Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Mammalian cells can use exogenous isoprenols to generate isoprenoid diphosphate substrates for protein isoprenylation, but the mechanism, efficiency, and biological importance of this process are not known. We developed mass spectrometry-based methods using chemical probes and newly synthesized stable isotope-labeled tracers to quantitate incorporation of exogenously provided farnesol, geranylgeraniol, and unnatural analogs of these isoprenols containing an aniline group into isoprenoid diphosphates and protein isoprenylcysteines by cultured human cancer cell lines. We found that at exogenous isoprenol concentrations >10 μM, this process can generate as much as 50% of the cellular isoprenoid diphosphate pool used for protein isoprenylation. Mutational activation of p53 in MDA-MB-231 breast cancer cells up-regulates the mevalonate pathway to promote tumor invasiveness. p53 silencing or pharmacological inhibition of HMG-CoA reductase in these cells decreases protein isoprenylation from endogenously synthesized isoprenoids but enhances the use of exogenous isoprenols for this purpose, indicating that this latter process is regulated independently of the mevalonate pathway. Our observations suggest unique opportunities for design of cancer cell-directed therapies and may provide insights into mechanisms underlying pleiotropic therapeutic benefits and unwanted side effects of mevalonate pathway inhibition.
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Registered trials
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.