β-Tubulin

β-Tubulin forms the α/β-tubulin heterodimer that polymerizes into microtubules, supporting cell division, intracellular transport, axon formation, and cilia function^[1]. Mechanistically, β-tubulin carries the exchangeable and hydrolysable nucleotide site; β-tubulin-bound GTP hydrolysis after lattice incorporation drives microtubule dynamic instability^[2]. Therefore, β-tubulin biology connects structural cytoskeleton organization with mitotic spindle function and microtubule-dependent intracellular trafficking^[1][2]. In disease models, TUBB3 mutations produce malformation of cortical development and neuronal migration defects, linking βIII-tubulin to neurodevelopmental research^[3]. In cancer models, class III β-tubulin overexpression confers resistance to paclitaxel and vinorelbine, while siRNA-mediated downregulation increases sensitivity to these drugs^[4]. Compared with class I β-tubulin, class III β-tubulin shows 92% similarity, carries Arg^277 instead of Ser^277, and this substitution alters the loop associated with stable paclitaxel binding^[4]. For experimental applications, colchicine-site agents including 2-MeOE2, colchicine, STX140, ENMD1198, and STX243 retained efficacy despite altered class III β-tubulin expression, supporting binding-site-focused inhibitor selection in taxane-refractory breast cancer models^[4]. Microtubule-targeted drugs can suppress microtubule dynamics without changing microtubule mass, producing mitotic block and apoptosis^[5].

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