Evidence map›Paper›PMID 28298489›Full record

ArticleMolecular biology of the cell2017

Mechanisms of kinetic stabilization by the drugs paclitaxel and vinblastine.

Brian T Castle, Seth McCubbin, Louis S Prahl, Jordan N Bernens, David Sept, David J Odde

Abstract read
In one paragraph

Article in Molecular biology of the cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
5.3field-weighted citation impact, top 3% 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

33 citing papers in PubMed, 70 citations in OpenAlex.

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  11. Melanoma therapeutics: a literature review.Journal of biomedical research · 2022
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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

6 authors at 2 institutions in 1 country.

Brian T CastleDepartment of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455.
Seth McCubbinDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109.
Louis S PrahlDepartment of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455.
Jordan N BernensDepartment of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455.
David SeptDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109.
David J OddeDepartment of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455 oddex002@umn.edu.
University of Minnesota · USUniversity of Michigan–Ann Arbor · US

Funding

MICHIGAN MOLECULAR BIOPHYSICS TRAINING PROGRAMT32GM008270 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BROOKS, CHARLES L · 1988 to 2012
$4.5M
Modeling Microtubule Dynamics in MitosisR01GM071522 · NIGMS · UNIVERSITY OF MINNESOTA · PI ODDE, DAVID J. · 2006 to 2013
$2.7M
Microtubule Mechanics at the NanoscaleR01GM076177 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ODDE, DAVID J., SEPT, DAVID · 2007 to 2015
$2.5M
Integrative Training Program in NeuroimagingT32EB008389 · NIBIB · UNIVERSITY OF MINNESOTA · PI CHEN, WEI · 2008 to 2019
$1.4M
NIBIB NIH HHS T32 EB008389NIGMS NIH HHS R01 GM071522NIGMS NIH HHS R01 GM076177NIGMS NIH HHS T32 GM008270
6 · The paper itself

Abstract

Microtubule-targeting agents (MTAs), widely used as biological probes and chemotherapeutic drugs, bind directly to tubulin subunits and "kinetically stabilize" microtubules, suppressing the characteristic self-assembly process of dynamic instability. However, the molecular-level mechanisms of kinetic stabilization are unclear, and the fundamental thermodynamic and kinetic requirements for dynamic instability and its elimination by MTAs have yet to be defined. Here we integrate a computational model for microtubule assembly with nanometer-scale fluorescence microscopy measurements to identify the kinetic and thermodynamic basis of kinetic stabilization by the MTAs paclitaxel, an assembly promoter, and vinblastine, a disassembly promoter. We identify two distinct modes of kinetic stabilization in live cells, one that truly suppresses on-off kinetics, characteristic of vinblastine, and the other a "pseudo" kinetic stabilization, characteristic of paclitaxel, that nearly eliminates the energy difference between the GTP- and GDP-tubulin thermodynamic states. By either mechanism, the main effect of both MTAs is to effectively stabilize the microtubule against disassembly in the absence of a robust GTP cap.

Indexed as

AnimalsComputer SimulationImage Processing, Computer-AssistedKineticsMicroscopy, FluorescenceMicrotubule-Associated ProteinsMicrotubulesPaclitaxelSwineThermodynamicsTubulinVinblastineMicrotubule-Associated ProteinsPaclitaxelTubulinVinblastine

Identifiers

PMID28298489
PMCPMC5415019
OpenAlexW2606557370

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.