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Tubulin alpha and beta chains are highly conserved cytoskeletal proteins that form the heterodimeric subunit of microtubules, which are crucial for maintaining cell shape, enabling intracellular transport, and orchestrating proper chromosome segregation during cell division. Each monomer possesses a similar structure of beta-sheets and alpha-helices and binds guanine nucleotides (GTP), with the alpha subunit’s GTP nonexchangeable and the beta subunit’s GTP hydrolyzed during microtubule dynamics. Tubulin exists as multiple isotypes and undergoes post-translational modifications that regulate its functions in both normal and disease states, especially in cancer where differential expression serves as a target for chemotherapy agents such as paclitaxel and vinca alkaloids. Dysfunction, mutation, and altered expression of tubulin are implicated in cancer drug resistance, neurodegenerative diseases (tubulinopathies), and immune/inflammatory disorders. Because microtubules are generally cold sensitive and integral to multiple essential cellular processes, tubulin-targeting drugs have therapeutic efficacy but also considerable safety concerns, especially neurotoxicity.
Inhibition/stabilization of microtubule polymerization (e.g., taxanes stabilize, vinca alkaloids inhibit polymerization); Interference with mitotic spindle formation (antimitotic mechanism); Induction of cell cycle arrest and apoptosis
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