Inhibition by p-bromophenacyl bromide of microtubule assembly in vitro.

Introduction Microtubules (MTs) play a central role in a variety of cellular phenomena including cell division, cell morphology and intracellular transport [ 11. Pharmacological studies of MT function and assembly involve the use of a range of MT poisons. Such agents can disrupt the control of MT dynamics either by stabilizing, e.g. taxol [2, 31, or destabilizing e.g. MTs [4-71, usually through direct interactions with either tubulin [ 3-61 or microtubule-associated proteins (MAPs) [7]. Colchicine and some of its derivatives, podophyllotoxin and the benzimidazole compounds prevent MT assembly by binding directly to tubulin [ l , 4-71. Colchicine is the most studied MT poison and was instrumental in the early identification of tubulin as the major protein subunit of MT [8]. It is a tropolene derivative with a single binding site on the P-tubulin subunit. Podophyllotoxin interacts with the same binding site [9], unlike the Vinca alkaloids, which bind to another region of tubulin [ 101. Concentrations of colchicine lower than 1 0 ' ~ can cause mitotic arrest by blocking spindle formation. The disassembly by colchicine of interphase MT in cultured cells results in the collapse of vimentin filaments to form perinuclear aggregates