Tubulin assembly and the mechanisms of action of interfacial antitumor drugs

Self-assembly of αβ-tubulin dimers into microtubules involves the switching of tubulin monomers from a curved conformation into the straight conformation, which is driven by the assembly contacts and fine-tuned by GTP/GDP. Several known microtubule inhibitors bind to curved tubulin, either at the colchicine site at the association interface between tubulin monomers or at the vinblastine site formed between tubuliin dimers.

We have found that recently discovered antitumor drugs (PM060481) have a distinct mechanism and bind at a new site at the β-tubulin plus end, impairing the association of a next tubulin dimer at the microtubule end (Pera 2013; Prota 2014)(in collaboration with JF Diaz, other labs at CIB and PharmaMar).