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 to tubulin in the absence of microtubule-associated proteins. Although recent studies have implicated beta-tubulin as the site of PTX binding, no information is available that relates alpha-tubulin to the binding site. In an effort to understand whether the alpha-tubulin is involved in the drug binding, we have studied the assembly of alpha-tubulin isoforms in the presence of PTX. The assembly results in the presence of 10 microM paclitaxel (PTX) show that the isoforms assemble at differential rates. The rate of assembly for tyrosinated M alpha 1/2 is about three-fold higher than that of the nontyrosinated M alpha 1/2 isoform. Such a strikingly different assembly behavior of the alpha-tubulin isoforms indicates that alpha-tubulin may be involved in the interaction of PTX with microtubules.
Banerjee
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A
Department of Biochemistry, University of Texas Health Science Center, San Antonio 78284-7760, USA.
Kasmala
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LT
D000595:Amino Acid Sequence; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001665:Binding Sites / Q000235:genetics; D001921:Brain / Q000378:metabolism*; D002417:Cattle; D007700:Kinetics; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D017239:Paclitaxel / Q000494:pharmacology*; D011485:Protein Binding; D017421:Sequence Analysis; D014404:Tubulin / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D014404:Tubulin; D017239:Paclitaxel