Microtubule bundling

Marshall, J., and Holberton, D. V. (1993). Sequence and structure of a new coiled-coil protein from a microtubule bundle in Giardia. J. Mol. Biol. 231, 521-530. 

Phase I clinical studies have recently been completed with Epo D, and phase II trials with the compound are now ongoing together with an additional phase I smdy [sponsored by Kosan Biosciences (as KOS-862)]. As for BMS-247550, KOS-862 was demonstrated to induce microtubule bundling in patient PBMCs, and several tumor responses have been noted in the phase I studies. ... 

Brandt R, Lee G (1994) assembly Orientation, and stability of microtubule bundles induced by a fragment of tau protein. Cell Motil Cytoskeleton 28 143-154 Buee L, Bussiere T, Buee-Scherrer V, Delacourte A, Hof PR (2000) Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res Brain Res Rev 33 95-130 Burn DJ, Jaros E (2001) Multiple system atrophy cellular and molecular pathology. J Clin Pathol Mol Pathol 54 419 26... 

Mishima, M., Kaitna, S., Glotzer, M. (2002). Central spindle assembly and cytokinesis require a kinesin-like protein/RhoGAP complex with microtubule bundling activity. Developmental CeU, 2, 41-54. 

Docetaxel is the second representative of the new entity of drugs that have a unique taxane ring in common, such as the one seen in pachtaxel. Being more efficacious than paclitaxel, docetaxel is used in ovarian cancer. Paclitaxel and docetaxel inhibit microtubule depolymerization, thereby reducing the formation of stable microtubule bundles (see also Figure 15). 

A364 -> T [116]. BMS-247550 has a potent tubulin polymerisation capacity (2,5 fold more potent as Taxol), a broad cytotoxicity (mean IC50 of 3.9 nM) and is efficacious in vivo after i.v. and p.o application [115]. A MTD with neutropenia as DLT (without G-CSF co-treatment) was determined and objective responses in breast and cervical cancer patients refractory to prior taxane therapy were observed [117]. In a clinical trial, the formation of microtubule bundles in peripheral blood mononuclear cells (PBMCs) was monitored and cell death occurred after peak microtubule bundle formation [118]. 

Paclitaxel binds specifically to /3-tubulin and antagonizes the disassembly of microtubules bundles of microtubules and aberrant structures derived from microtubules appear in the M phase of the cell cycle, causing mitotic arrest. Cell kilhng is dependent on both drug concentration and duration of cell exposure. Drugs that block cell cycle progression prior to mitosis antagonize the toxic effects of taxanes. 

The last two terms in Eqs. (2.13), (2.14) are linearized near the mean density, Po = (p). The last term in Eq.(2.13) regularizes the short-wave instahility when the diffusion term changes sign for po > pt, = l/4i3. This instahility leads to strong density variations associated with the formation of microtubule bundles, see Eig. 5. 

Note characteristic nuclear cleft (NC), extensive cytoplasmic canaScular system (CS) and peripheral microtubule bundles arrows). Scale bar = 0.5 pm. 

The main mode of therapeutic action of docetaxel is the suppression of microtubule dynamic assembly and disassembly, rather than microtubule bundling leading to apoptosis, or the blocking of bcl-2 [17]. 

Church K. and Lin H.P.P. 1982. Meiosis in Drosophila melanogaster. The prometaphase-1 kinetochore microtubule bundle and kinetochore orientation in males. J. Gell Biol. 93 365-373. 

Sharp D.J., McDonald K.L., Brown H.M., Matthies H.J., Walczak C., Vale R.D., Mitchison T.J., and Scholey J.M. 1999. The bipolar kinesin, KLP61F, associates with interpolar microtubule bundles within mitotic spindles of Drosophila early embryos. J. Cell Biol. 144 125-138. 

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