ArticleBiochemical and biophysical research communications2010
A novel statin-mediated "prenylation block-and-release" assay provides insight into the membrane targeting mechanisms of small GTPases.
Article in Biochemical and biophysical research communications, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 34 citations in OpenAlex.
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- Evaluation of the cellular impact of missense variants in low-density lipoprotein receptor-related protein 6 (LRP6) associated with cardiovascular diseases in HeLa and HEK293T cell lines.Frontiers in cell and developmental biology · 2026Article
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- Hartnup disease-causing SLC6A19 mutations lead to B0AT1 aberrant trafficking and ACE2 mis-localisation implicating the endoplasmic reticulum protein quality control.Frontiers in cell and developmental biology · 2025Article
- Vesicular trafficking is a key determinant of the statin response in acute myeloid leukemia.Blood advances · 2022Article
- Cholesterol metabolism drives regulatory B cell IL-10 through provision of geranylgeranyl pyrophosphate.Nature communications · 2020Article
- Statin-specific inhibition of Rab-GTPase regulates cPKC-mediated IKs internalization.Scientific reports · 2019Article
- Endoplasmic reticulum quality control of LDLR variants associated with familial hypercholesterolemia.FEBS open bio · 2019Article
- Fluvastatin inhibits Rab5-mediated IKs internalization caused by chronic CaJournal of molecular and cellular cardiology · 2019Article
- Identification of Receptor Ligands in Apo B100 Reveals Potential Functional Domains.The protein journal · 2018Article
- Metabolic Labeling with an Alkyne-modified Isoprenoid Analog Facilitates Imaging and Quantification of the Prenylome in Cells.ACS chemical biology · 2016Article
- Intracellular oxygen determined by respiration regulates localization of Ras and prenylated proteins.Cell death & disease · 2015Article
- HMGCR is necessary for the tumorigenecity of esophageal squamous cell carcinoma and is regulated by Myc.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- An adenosine-mediated signaling pathway suppresses prenylation of the GTPase Rap1B and promotes cell scattering.Science signaling · 2013Article
- A Novel Aberrant Splice Site Mutation in RAB23 Leads to an Eight Nucleotide Deletion in the mRNA and Is Responsible for Carpenter Syndrome in a Consanguineous Emirati Family.Molecular syndromology · 2013Article
- Apoptosis, autophagy and ER stress in mevalonate cascade inhibition-induced cell death of human atrial fibroblasts.Cell death & disease · 2012Article
- Rab GTPases as regulators of endocytosis, targets of disease and therapeutic opportunities.Clinical genetics · 2011Review
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
Abstract
Ras super-family small GTPases regulate diverse cellular processes such as vesicular transport and signal transduction. Critical to these activities is the ability of these proteins to target to specific intracellular membranes. To allow association with membranes Ras-related GTPases are post-translationally modified by covalent attachment of prenyl groups to conserved cysteine residues at or near their C-terminus. Here we used the HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase (HMGCR) inhibitor mevastatin to develop a 'prenylation block-and-release' assay that allows membrane targeting of prenylated proteins to be visualized in living cells. Using this assay we investigated the cytosol to membrane targeting of several small GTPases to compartments of the secretory and endocytic pathways. We found that all Rabs tested were targeted directly to the membrane on which they reside at steady-state and not via an intermediate location as reported for Ras and Rho proteins. However, we observed that the kinetics of cytosol to membrane targeting differed for each Rab tested. Comparison of the mevastatin sensitivity and kinetics of membrane targeting of Rab23, Rab23 prenylation motif mutants and H-Ras revealed that these parameters are strongly dependent upon the prenyl transferase with Rab geranylgeranyl transferase substrates exhibiting higher sensitivity and requiring greater time to recover from mevastatin inhibition than farnesyl transferase substrates. We propose that this assay is a useful tool to investigate the kinetics, biological functions and the mechanisms of membrane targeting of prenylated proteins.
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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.