Microtubules (MTs) have attracted interest and experimental attention in part because they are involved in numerous cellular processes and in part because they are intriguingly dynamic. Many studies with light and electron microscopes have shown that MTs can change their location and extent of polymerization, depending on the physiological state of the cell. Efforts to study this dynamism and t...

A subset of mutant cell lines selected for resistance to the antitumor drug paclitaxel are unable to progress normally through mitosis unless the drug is present in the growth medium. Without paclitaxel the cells form defective spindles, undergo aberrant mitoses, fail to complete cell division and eventually die. Analysis of these drug-dependent cells revealed a low amount of microtubule polyme...

In this study, a variety of original ligands related to Combretastatin A-4 and isoCombretastatin A-4, able inhibit the tubulin polymerization into microtubules, was designed, synthesized, evaluated. Our lead compound 15d having quinazoline as A-ring 2-substituted indole B-ring separated by N-methyl linker displayed remarkable sub-nanomolar level cytotoxicity (IC50 < 1 nM) against 9 human cancer...

The semisynthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO) has several biological activities, including the induction of apoptosis in many cancer cell lines. To identify potential protein targets, immobilized biotinylated CDDO was used to screen the proteome of a human lymphoma cell line (U937) sensitive to CDDO-induced apoptosis. Tubulin was identified as one of se...

Microtubules are polymers of αβ-tubulin heterodimers essential for all eukaryotes. Despite sequence conservation, there are significant structural differences between microtubules assembled in vitro from mammalian or budding yeast tubulin. Yeast MTs were not observed to undergo compaction at the interdimer interface as seen for mammalian microtubules upon GTP hydrolysis. Lack of compaction migh...

Arsenic exhibits a differential toxicity to cancer cells. At a high concentration (>5 microM), As2O3 causes acute necrosis in various cell lines. At a lower concentration (0.5-5 microm), it induces myeloid cell maturation and an arrest in metaphase, leading to apoptosis. As2O3-treated cells have features found with both tubulin-assembling enhancers (Taxol) and inhibitors (colchicine). Prior tre...