α-Tubulin detyrosination links the suppression of MCAK activity with taxol cytotoxicity.

ABSTRACT: 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 mitos

SUBMITTER: Lopes D 

PROVIDER: S-EPMC9723805 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature