Tubulin and microtubule-associated proteins (Tubulin/MAPs)

Tubulin and microtubule-associated proteins (MAPs) are the fundamental structural and regulatory components of the eukaryotic cytoskeleton. Tubulin exists as alpha and beta heterodimers that polymerize into dynamic, hollow tubes called microtubules, which are essential for maintaining cell architecture, facilitating intracellular transport, and forming the mitotic spindle during cell division [1, 2]. MAPs, such as Tau and stathmin, further regulate these processes by stabilizing or destabilizing the microtubule network in response to cellular signals [3, 5, 12]. In clinical practice, tubulin is a premier therapeutic target for cancer, where drugs like taxanes and vinca alkaloids disrupt spindle dynamics to induce cell cycle arrest and apoptosis [1, 4]. Beyond oncology, the dysregulation of MAPs is a hallmark of neurodegenerative conditions like Alzheimer's disease, where Tau protein aggregation leads to neuronal dysfunction [7, 11]. Despite their efficacy, tubulin-targeting therapies are often limited by dose-limiting toxicities such as peripheral neuropathy, caused by the disruption of microtubule-dependent axonal transport [2, 11].

Other names

MicrotubulesAlpha-tubulinBeta-tubulinMicrotubule-associated proteinsMAPsTau proteinStathminEnd-binding protein 1 (EB1)

Drugs targeting this system act by modulating the dynamic instability of microtubules. Microtubule-stabilizing agents (e.g., taxanes) bind to polymerized tubulin to prevent disassembly, while microtubule-destabilizing agents (e.g., vinca alkaloids) bind to tubulin dimers to inhibit polymerization [1, 2]. Both mechanisms lead to mitotic arrest at the metaphase-anaphase transition, ultimately triggering apoptosis in rapidly dividing cells [4, 5].