The interaction of tubulin-microtubule poison complexes with anti-tubulin antisera has been investigated using radioimmunoassay. The binding of the major antiserum used in this study to tubulin does not interfere with the binding of colchicine to the tubulin or affect the decay of the colchicine-binding activity of the tubulin. Conversely, if colchicine is incubated with the tubulin, forming tu...

Vinblastine sulphate (VLB) is known to induce in vivo formation of tubulin paracrystals in sea-urchin eggs. Corresponding paracrystals have been prepared in the presence of both vinblastine sulphate and other mitoclasic agents. Careful standardization of conditions was required to restrict the formation of alternative forms of the paracrystals induced by vinblastine alone. Comparisons were made...

The tubulin vinca domain is the target of widely different microtubule inhibitors that interfere with the binding of vinblastine. Although all these ligands inhibit the hydrolysis of GTP, they affect nucleotide exchange to variable extents. The structures of two vinca domain antimitotic peptides--phomopsin A and soblidotin (a dolastatin 10 analogue)--bound to tubulin in a complex with a stathmi...

Two types of ultrastructurally distinct tubulin paracrystals have been induced in sea-urchin eggs with vinblastine sulphate (VLB) under different sets of conditions. One type of paracrystal appears to consist of hexagonally-close packed microtubules and closely resembles paracrystals present in mammalian cells treated with vinblastine or vincristine sulphate, but not previously reported in sea-...

We have isolated chromosomes from Chinese hamster ovary cells arrested in mitosis with vinblastine and examined the interactions of their kinetochores with purified tubulin in vitro. The kinetochores nucleate microtubule (MT) growth with complex kinetics. After an initial lag phase, MTs are continuously nucleated with both plus and minus ends distally localized. This mixed polarity seems incons...

Halichondrin B is an antimitotic drug that inhibits microtubule assembly. To understand the molecular details of its interaction with tubulin, we investigated the binding of two halichondrin B analogues, eribulin (previously, ER-086526, E7389) and ER-076349, to tubulin by quantitative analytical ultracentrifugation. Eribulin is currently undergoing phase III clinical trials for cancer; ER-07634...

Surface-exposed proteins of vinblastine-sensitive human lymphoid cell line of leukemic origin (CCRF-CEM) were examined by the lactoperoxidase-catalyzed iodination and two-dimensional polyacrylamide gel electrophoresis methods. Spots which comigrate with bovine brain tubulin and rabbit muscle actin were prominently labeled in the whole membrane but not in the high-speed supernatant fraction of t...

The cytotoxic, antimitotic, and growth inhibition properties of a photoactive analogue of vinblastine, N-(p-azidobenzoyl)-N'-beta-aminoethylvindesine (NABV), and vinblastine on P388 murine leukemia cells were compared. After 72-h exposure, the 50% drug-inhibitory concentrations for exponentially growing P388 leukemic cells were 1.2 nM for NABV and 0.6 nM for vinblastine. The ultrastructural eff...

Dilantin (phenytoin) is a commonly used antiepileptic agent that is known to decrease conductance of sodium and calcium ions and delay outward potassium currents. Separate from its antiseizure activity, dilantin interferes with microtubule protein polymerization. It induces metaphase arrest and potentiates the effects of the antimitotics vincristine and vinblastine in cell culture. We show here...

The distribution of microtubules in Chlamydomonas reinhardtii suggests that they are involved in mitosis, cell and nuclear cleavage, and generation of flagella. Vinblastine, colchicine, and podophyllotoxin bind to the protein building block of microtubules (tubulin) and prevent normal assembly. Mutants resistant to these "antitubulin" drugs are candidates to have alterations in tubulin primary ...