biostudies-literatureLopes DFundação para a Ciência e a TecnologiaEuropean Research CouncilEuropean Union’s Horizon 2020La Caixa Health ResearchEuropean Regional Development Funde202205092https://www.ebi.ac.uk/biostudies/studies/S-EPMC9723805biostudies-literatureUnknown222(2)α/β-Tubulin posttranslational modifications (PTMs) generate microtubule diversity, but whether they account for cancer cell resistance to microtubule-targeting drugs remains unknown. Here, we performed a pilot dissection of the "cancer tubulin code" using the NCI-60 cancer cell panel. We found that acetylated, detyrosinated, and ∆2-α-tubulin that typically accumulate on stable microtubules were uncoupled in many cancer cells. Acetylated α-tubulin did not affect microtubule dynamics, whereas its levels correlated with, but were not required for, taxol-induced cytotoxicity. In contrast, experimental increase of α-tubulin detyrosination, and/or depletion of the detyrosination-sensitive microtubule-depolymerizing enzyme MCAK, enhanced taxol-induced cytotoxicity by promoting cell death in mitosThe Journal of cell biologyα-Tubulin detyrosination links the suppression of MCAK activity with taxol cytotoxicity.PMC9723805/135077/2017PTDC/MED-SFRH/681443/3479/2020NORTE-01-0145-FEDER-000051/PR/HR21/52410025Lopes DSeabra ALMaiato HOrr Bfalseα-Tubulin detyrosination links the suppression of MCAK activity with taxol cytotoxicity.α/β-Tubulin posttranslational modifications (PTMs) generate microtubule diversity, but whether they account for cancer cell resistance to microtubule-targeting drugs remains unknown. Here, we performed a pilot dissection of the "cancer tubulin code" using the NCI-60 cancer cell panel. We found that acetylated, detyrosinated, and ∆2-α-tubulin that typically accumulate on stable microtubules were uncoupled in many cancer cells. Acetylated α-tubulin did not affect microtubule dynamics, whereas its levels correlated with, but were not required for, taxol-induced cytotoxicity. In contrast, experimental increase of α-tubulin detyrosination, and/or depletion of the detyrosination-sensitive microtubule-depolymerizing enzyme MCAK, enhanced taxol-induced cytotoxicity by promoting cell death in mitos2023-01-01T00:00:00Z2023 Feb2025-04-19T04:20:27.056Z2025-04-19T04:20:27.056ZS-EPMC97238053645906510.1083/jcb.202205092