Microtubules are subjected to a variety of post-translational modifications (PTMs). The combination of different α- and β-tubulin isoforms and PTMs are referred to as the tubulin code. PTMs are generated by a suite of enzymes thought to affect tubulin-interacting proteins. One PTM is the cyclic removal and ligation of the C-terminal tyrosine of α-tubulin. This has been implicated in cellular processes such as mitosis, cardiomyocyte contraction, and neuronal function. Recently, vasohibins (VASHs) were identified as the first tubulin-detyrosinating enzymes, A cell-autonomous role for VASHs in regulating the cytoskeleton was unexpected due to their previous association with angiogenesis. This review discusses the functionality of the tubulin detyrosination cycle, the biology of VASHs, and highlights the emerging questions accompanying this link.
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