نتایج جستجو برای: tubulin polymerization
تعداد نتایج: 40472 فیلتر نتایج به سال:
Molecules that alter the normal dynamics of microtubule assembly and disassembly include many anticancer drugs in clinical use. So far all such therapeutics target β-tubulin, and structural biology has explained the basis of their action and permitted design of new drugs. However, by shifting the profile of β-tubulin isoforms, cancer cells become resistant to treatment. Compounds that bind to α...
Using a single nucleotide polymorphism association study in 52 men with prostate cancer receiving docetaxel, we found that individuals carrying two copies of the CYP1B1*3 polymorphic variant had a poor prognosis after docetaxel-based therapies compared with individuals carrying at least one copy of the CYP1B1*1 allele (30.6 versus 12.8 months; P=0.0004). The association between CYP1B1*3 and res...
Colchicine.tubulin complex (CD) inhibits microtubule assembly. We examined this inhibition under conditions where spontaneous nucleation was suppressed and assembly was restricted to an elongation polymerization. We found that CD inhibited assembly by a mechanism which preserved the ability of microtubule ends to add tubulin. This observation is inconsistent with the end-poisoning model which r...
We have compared tubulin from exponentially growing and mitotic enriched populations of suspensioncultured HeLa cells. The proportion of the protein in the cell extract that was tubulin (4.6%) was the same in populations of both mitotic and log phase cells. The self assembly and copolymerization activity of extract tubulin were also compared for the two populations of cells. Approximately 60% o...
The effects on tubulin dynamics of paclitaxel, ortataxel and two recently developed taxol derivatives bearing a five-membered heterocyclic ring fused at the 1,14 position were analysed by means of molecular dynamic simulations and the MM-PBSA approach. Tubulin polymerization kinetics and microtubule morphology assays were also conducted, providing support to computational results. In particular...
The taccalonolides are highly acetylated steroids that stabilize cellular microtubules and overcome multiple mechanisms of taxane resistance. Recently, two potent taccalonolides, AF and AJ, were identified that bind to tubulin directly and enhance microtubule polymerization. Extensive studies were conducted to characterize these new taccalonolides. AF and AJ caused aberrant mitotic spindles and...
Dihydroxynaphthyl aryl ketones 1-5 have been evaluated for their abilities to inhibit microtubule assembly and the binding to tubulin. Compounds 3, 4 and 5 displayed competitive inhibition against colchicine binding, and docking analysis showed that they bind to the tubulin colchicine-binding pocket inducing sheets instead of microtubules. Remarkable differences in biological activity observed ...
alpha-, beta-, and gamma-tubulins are evolutionarily highly conserved members of the tubulin gene superfamily. While the abundant members, alpha- and beta-tubulins, constitute the building blocks of cellular microtubule polymers, gamma-tubulin is a low abundance protein which localized to the pericentriolar material and may play a role in microtubule assembly. To test whether gamma-tubulin medi...
The recent observation of GTP-promoted polymerization of a single septin polypeptide suggests that this protein has tubulin-like biochemical properties. This model cannot, however, explain the GTP-biochemistry of heteromeric septin complexes from cytosol.
Microtubule-associated proteins (MAPs) promote tubulin polymerization, whereas colchicine inhibits this process. In this paper, MAPs have been shown to inhibit colchicine binding to tubulin in a competitive manner. Attempts were made to identify which of the MAPs fraction(s) was responsible; both tau protein (a thermostable molecule with a molecular weight of approximately 70,000) and a high mo...
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