Beta-tubulin at microtubule plus-end (TUBB (plus-end))

Beta-tubulin at the microtubule plus-end is a critical regulatory site for the assembly and dynamics of the eukaryotic cytoskeleton [1, 15]. Microtubules are polar polymers of alpha- and beta-tubulin heterodimers, where the plus-end is characterized by an exposed beta-tubulin subunit and is the primary site of rapid polymerization and interaction with regulatory proteins [9, 14]. This specific site is a potent therapeutic target, particularly for the drug eribulin, which binds with high affinity to a small number of sites at the growing plus-end to suppress microtubule growth without affecting shortening [3, 5]. By disrupting the dynamic instability of microtubules, drugs targeting this site induce irreversible mitotic arrest in the G2/M phase, leading to apoptosis in rapidly dividing cancer cells [2, 4]. Beyond its role in mitosis, targeting beta-tubulin at the plus-end affects non-mitotic processes such as intracellular transport, cell migration, and tumor angiogenesis [5, 16]. Clinically, this target is significant in the treatment of metastatic breast cancer and soft tissue sarcomas, though its modulation is often associated with dose-limiting toxicities like peripheral neuropathy and neutropenia [1, 15].

Other names

Microtubule plus-endGTP-beta-tubulinEribulin binding siteMaytansine binding site

Inhibition of microtubule growth and suppression of dynamic instability by binding to high-affinity sites on beta-tubulin at the growing (plus) ends of microtubules [1, 3]. This binding prevents the addition of new tubulin dimers, leading to irreversible mitotic arrest in the G2/M phase and subsequent apoptosis [2, 4, 5].