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Data · dataset · 2015

Eribulin disrupts EB1-microtubule plus-tip complex formation

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Eribulin mesylate is a synthetic analog of halichondrin B known to bind tubulin and microtubules, specifically at their protein rich plus-ends, thereby dampening microtubule (MT) dynamics, arresting cells in mitosis, and inducing apoptosis.

Description

The proteins which bind to the MT plus-end are known as microtubule plus-end tracking proteins (+TIPs) and have been shown to promote MT growth and stabilization. Eribulin's plus-end binding suggests it may compete for binding sites with known +TIP proteins such as End-binding 1 (EB1).

To better understand the impact of eribulin plus-end binding in regard to the proteins which normally bind there, cells expressing GFP-EB1 were treated with various concentrations of eribulin. In a concentration dependent manner, GFP-EB1 became dissociated from the MT plus-ends following drug addition. Similar results were found with immuno-stained fixed cells.

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Cells treated with low concentrations of eribulin also showed decreased ability to migrate, suggesting the decrease in MT dynamics may have a downstream effect. Extended exposure of eribulin to cells leads to total depolymerization of the MT array. Taken together, these data show eribulin effectively disrupts EB1 +TIP complex formation, providing mechanistic insights into the impact of eribulin on MT dynamics.

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Cancer · Chemistry

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Provenance · 1 source records, 13 field assertions
SourceKeyLast seenRaw
DataCite10.6084/m9.figshare.1232088.v412 d agoJSON v1
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concepts[disease].local:disease:cancermapping · DataCitevocabulary-mapper@1.0.0keywords['Cancer']
concepts[field].fos:biological-sciencessource · DataCiteconnector:datacite@1.0.0
concepts[field].fos:clinical-medicinesource · DataCiteconnector:datacite@1.0.0
concepts[field].fos:health-sciencessource · DataCiteconnector:datacite@1.0.0
concepts[field].local:field:chemistrymapping · DataCitevocabulary-mapper@1.0.0keywords['Chemistry']
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