Alpha-tubulin C-terminal tyrosine (Tyr-tubulin)

Alpha-tubulin C-terminal tyrosine refers to the specific post-translational modification state of alpha-tubulin where a tyrosine residue is present at the C-terminus. In most cells, alpha-tubulin is synthesized with this terminal tyrosine, which is subsequently removed by tubulin carboxypeptidases, specifically Vasohibin-1 (VASH1) and Vasohibin-2 (VASH2), once the tubulin is incorporated into polymerized microtubules [Aillaud et al., 2017, Science]. This removal creates detyrosinated tubulin (Glu-tubulin), a modification that is reversed by tubulin tyrosine ligase (TTL) only after the microtubule depolymerizes into soluble dimers [Ersfeld et al., 1993, J Cell Biol]. This tyrosination/detyrosination cycle acts as a critical component of the 'tubulin code,' regulating the recruitment and activity of molecular motors like kinesins and dyneins, as well as microtubule-associated proteins [Nieuwenhuis et al., 2017, Science]. Dysregulation of the alpha-tubulin tyrosination state is heavily implicated in various pathologies. In cancer, the loss of TTL expression leads to an accumulation of detyrosinated microtubules, which is associated with increased tumor aggressiveness, epithelial-to-mesenchymal transition, and poor patient prognosis [Kato et al., 2004, Cancer Research]. In the cardiovascular system, excessive detyrosination of microtubules increases the mechanical resistance of the cytoskeleton in cardiomyocytes, contributing to the stiffening and contractile dysfunction observed in heart failure [Chen et al., 2018, Nature Medicine]. Therapeutic strategies currently focus on small molecule inhibitors of VASH enzymes, such as Parthenolide or Epothilone Y, to reduce detyrosination and restore normal microtubule function in diseased tissues [Fonrose et al., 2007, Cancer Research].

Other names

Tyrosinated alpha-tubulinC-terminal tyrosine of alpha-tubulinAlpha-tubulin tyrosine residueTyr-alpha-tubulin

Modulation of the tubulin tyrosination cycle by inhibiting tubulin carboxypeptidases (VASH1/VASH2) to prevent detyrosination or supporting tubulin tyrosine ligase (TTL) activity to maintain the tyrosinated state, thereby regulating microtubule-protein interactions and cellular stability [Aillaud et al., 2017, Science; Nieuwenhuis et al., 2017, Science].