A previously undescribed tubulin binder.

Abstract

Microtubules (MTs) are key components of the cytoskeleton for all eukaryotes and are vital for cellular processes such as mitotic spindle formation, intracellular transport, vesicle formation, cellular signaling, and migration. These functions depend on the dynamic nature of MTs, which arises from the polymerization and depolymerization events of individual heterodimers, made up of α- and β-tubulin subunits (1). Strict control and appropriate regulation of the equilibrium between free tubulin and MTs is therefore critical for cell viability and has provided the basis for the development of several drugs used in treating cancer (2), autoimmune diseases (3), and neurological diseases (4). Understanding how the drugs bind to tubulin has proven invaluable not only in elucidating how they function, but also for designing new lead agents. In PNAS, Prota et al. add significant new insights into this field by defining a site within tubulin that is able to bind clinically relevant anticancer drugs in a manner that has not been previously described (5).