Studies on the Nocodazole-Induced GTPase Activity of Tubulin

Mejillano, Magdalena R.; Shivanna, B. D.; Himes, Richard H.

doi:10.1006/abbi.1996.0540

Cited by 40 publications

(31 citation statements)

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“…jejuni internalization is sensitive to microtubule inhibitors Binding and internalization assays were also performed with the C. jejuni F38011 and 81-176 clinical isolates, S. typhimurium and C. freundii in the presence of the microtubule inhibitor nocodazole (Table 6). Nocodazole binds b-tubulin, preventing tubulin polymerization, as well as enhances GTPase activity (Mejillano et al, 1996). Nocodazole had no effect on the binding of the C. jejuni isolates to the INT 407 cells, but did significantly inhibit the uptake of both isolates by the INT 407 cells in a dosedependent fashion.…”

Section: The Effect Of Cytochalasin D On C Jejuni Internalization Ismentioning

confidence: 92%

Maximal adherence and invasion of INT 407 cells by Campylobacter jejuni requires the CadF outer-membrane protein and microfilament reorganization

2003

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Section: The Effect Of Cytochalasin D On C Jejuni Internalization Ismentioning

confidence: 92%

Maximal adherence and invasion of INT 407 cells by Campylobacter jejuni requires the CadF outer-membrane protein and microfilament reorganization

2003

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“…Nocodazole causes microtubule depolymerization by quadrupling the rate of GTP hydrolysis on the tubulin dimer 24 and dramatically disrupts microtubule structure and function ( Figure 5G). Nocodazole also induces the activation of arginase.…”

Section: Posttranslational Activation Of Arginasementioning

confidence: 99%

Oxidized Low-Density Lipoprotein–Dependent Endothelial Arginase II Activation Contributes to Impaired Nitric Oxide Signaling

Ryoo

Lemmon

Soucy

et al. 2006

Circulation Research

162

186

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Abstract-Oxidized low-density lipoprotein (OxLDL) impairs NO signaling and endothelial function, and contributes to the pathogenesis of atherosclerosis. Arginase reciprocally regulates NO levels in endothelial cells by competing with NO synthase for the substrate L-arginine. In human aortic endothelial cells, OxLDL stimulation increased arginase enzyme activity in a time-and dose-dependent manner. Arginase activity reached its maximum as early as 5 minutes, was maintained for a period of more than 48 hours, and was associated with a reciprocal decrease in NO metabolite (NOx [nitrite and nitrate]) production. Furthermore, OxLDL induced arginase II mRNA expression after 4 hours. Small interfering RNA targeted to arginase II decreased both the quantity and the activity of arginase from baseline, prevented OxLDL-dependent increases in arginase activity, and induced an increase in NOx production. Immunofluorescence analysis revealed an association of arginase II with the microtubule cytoskeleton. Microtubule disruption with nocodazole caused a dramatic redistribution of arginase II to a diffuse cytosolic pattern, increased arginase activity, and decreased NOx production, which was restored in the presence of the specific arginase inhibitor (S)-(2-boronoethyl)-L-cysteine (BEC). On the other hand, epothilone B prevented microtubule disruption and inhibited OxLDL-dependent increases in arginase activity and attenuated OxLDL-dependent decreases in NOx. Preincubation of rat aortic rings with OxLDL resulted in an increase in arginase activity and a decrease in NOx production. This was reversed by arginase inhibition with the BEC. Thus, OxLDLs increase arginase activity by a sequence of regulatory events that involve early activation through decreased association with microtubules and a later increase in transcription. Furthermore, increased arginase activity contributes to OxLDL-dependent impairment of NOx production. Arginase, therefore, represents a novel target for therapy in atherosclerosis.

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“…In contrast, paclitaxel and its analogues actually promote microtubule polymer formation [3][4][5], albeit by acting at a different site on tubulin than colchicine. A variety of small molecules with diverse molecular scaffolds have been shown to bind tubulin at the colchicine site [6][7][8][9]. One class of these compounds receiving particular attention has been that based on the natural product combretastatin A-4 discovered by Pettit [10,11].…”

Section: Introductionmentioning

confidence: 99%

Docking and hydropathic scoring of polysubstituted pyrrole compounds with antitubulin activity

Tripathi

Fornabaio

Kellogg

et al. 2008

Bioorganic & Medicinal Chemistry

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Compounds that bind at the colchicine site of tubulin have drawn considerable attention with studies indicating that these agents suppress microtubule dynamics and inhibit tubulin polymerization. Data for eighteen polysubstituted pyrrole compounds are reported, including antiproliferative activity against human MDA-MB-435 cells and calculated free energies of binding following docking the compounds into models of αβ-tubulin. These docking calculations coupled with HINT interaction analyses are able to represent the complex structures and the binding modes of inhibitors such that calculated and measured free energies of binding correlate with an r 2 of 0.76. Structural analysis of the binding pocket identifies important intermolecular contacts that mediate binding. As seen experimentally, the complex with JG-03-14 (3,5-dibromo-4-(3,4-dimethoxyphenyl)-1H-pyrrole-2-carboxylic acid ethyl ester) is the most stable. These results illuminate the binding process and should be valuable in the design of new pyrrole-based colchicine site inhibitors as these compounds have very accessible syntheses.

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Studies on the Nocodazole-Induced GTPase Activity of Tubulin

Cited by 40 publications

References 0 publications

Maximal adherence and invasion of INT 407 cells by Campylobacter jejuni requires the CadF outer-membrane protein and microfilament reorganization

Maximal adherence and invasion of INT 407 cells by Campylobacter jejuni requires the CadF outer-membrane protein and microfilament reorganization

Oxidized Low-Density Lipoprotein–Dependent Endothelial Arginase II Activation Contributes to Impaired Nitric Oxide Signaling

Docking and hydropathic scoring of polysubstituted pyrrole compounds with antitubulin activity

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