Evidence map›Paper›PMID 20471365›Full record

ArticleBiochemical and biophysical research communications2010

A novel statin-mediated "prenylation block-and-release" assay provides insight into the membrane targeting mechanisms of small GTPases.

Bassam R Ali, Ian Nouvel, Ka Fai Leung, Alistair N Hume, Miguel C Seabra

Open access · hybridAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.2field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 34 citations in OpenAlex.

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  9. Fluvastatin inhibits Rab5-mediated IKs internalization caused by chronic CaJournal of molecular and cellular cardiology · 2019
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  13. 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 · 2014
    Article
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  17. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 2 countries.

Bassam R AliDepartment of Pathology, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates. bassam.ali@uaeu.ac.ae
Ian Nouvel
Ka Fai Leung
Alistair N Hume
Miguel C Seabra
Imperial College London · GB

Funding

Wellcome Trust 075498Wellcome Trust 075498/Z/04/Z
6 · The paper itself

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.

Indexed as

Cell MembraneGreen Fluorescent ProteinsHeLa CellsHumansHydroxymethylglutaryl-CoA Reductase InhibitorsLovastatinProtein PrenylationProtein Processing, Post-TranslationalProtein Transportrab5 GTP-Binding Proteinsrab GTP-Binding Proteinsras Proteinsenhanced green fluorescent proteinGreen Fluorescent ProteinsHydroxymethylglutaryl-CoA Reductase InhibitorsLovastatinmevastatinRAB23 protein, humanrab5 GTP-Binding Proteinsrab GTP-Binding Proteinsras Proteins

Identifiers

PMID20471365
PMCPMC2908739
OpenAlexW2068848560

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.