Defining the Biological Role of the
 Taxol-binding Region on Microtubules

Anti-cancer therapies like Taxol that hyper-stabilize microtubules are among the best cancer treatments discovered to date. When microtubule-DNA connections are disrupted with these compounds in dividing tumor cells, the cells often enter a programmed cell death pathway called apoptosis. However, we do not understand the molecular nature of the disrupted DNA attachments nor how that signals the apoptosis pathway. Based on accumulating evidence, we have developed a novel concept of selective microtubule stabilization: that these compounds mimic the effects of cellular factors located at attachment sites that would have access to the Taxol-binding site on microtubules. With a unique approach, we will determine whether a small, localized region of interaction with the Taxol-binding site can, indeed, stabilize the length of the microtubule. This is an innovative, testable concept with implications for understanding the biological role of the Taxol-binding site and the mechanisms that selectively stabilize microtubules at attachment sites.