Microtubule-assisted mechanism for functional metabolic macromolecular complex formation.
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ABSTRACT:
SUBMITTER: An S
PROVIDER: S-EPMC2919939 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Abstract 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. 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. 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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Project description:High-throughput techniques are leading to an explosive growth in the size of biological databases and creating the opportunity to revolutionize our understanding of life and disease. Interpretation of these data remains, however, a major scientific challenge. Here, we propose a methodology that enables us to extract and display information contained in complex networks. Specifically, we demonstrate that we can find functional modules in complex networks, and classify nodes into universal roles according to their pattern of intra- and inter-module connections. The method thus yields a 'cartographic representation' of complex networks. Metabolic networks are among the most challenging biological networks and, arguably, the ones with most potential for immediate applicability. We use our method to analyse the metabolic networks of twelve organisms from three different superkingdoms. We find that, typically, 80% of the nodes are only connected to other nodes within their respective modules, and that nodes with different roles are affected by different evolutionary constraints and pressures. Remarkably, we find that metabolites that participate in only a few reactions but that connect different modules are more conserved than hubs whose links are mostly within a single module.
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2014-06-30 | E-GEOD-48324 | biostudies-arrayexpress
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Project description:We sequenced mRNA of three dual perturbation experiments of E. coli K12 MG1655 changing both genetic and environmental conditions. Each dual perturbation experiment consists of four RNA-seq samples (WT, WT+nutrient supplementation, transcription factor KO, transcription factor KO+nutrient supplementation). The three conditions are: 1) adenine supplementation/nac KO, 2) L-tryptophan supplementation/cra KO, 3) anaerobic/mntR KO.
2014-06-30 | GSE48324 | GEO
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