DIFFERENTIAL ASSEMBLY KINETICS OF ALPHA-TUBULIN ISOFORMS IN THE PRESENCE OF PACLITAXEL

The antitumor drug paclitaxel (PTX) inhibits cell growth by binding to microtubules, the eukaryotic structures consisting of alpha- and beta -tubulin. PTX also promotes the assembly of tubulin in the absence of microtubule-associated proteins. Although recent studies have implicat ed beta-tubulin as the site of PTX binding, no information is availabl e that relates alpha-tubulin to the binding site. In an effort to unde rstand whether the alpha-tubulin is involved in the drug binding, we h ave studied the assembly of alpha-tubulin isoforms in the presence of PTX. The assembly results in the presence of 10 mu M paclitaxel (PTX) show that the isoforms assemble at differential rates. The rate of ass embly for tyrosinated M alpha 1/2 is about three fold higher than that of the nontyrosinated M alpha 1/2 isoform, Such a strikingly differen t assembly behavior of the alpha-tubulin isoforms indicates that alpha -tubulin may be involved in the interaction of PTX with microtubules. (C) 1998 Academic Press.