The Tubulin Code in Mitosis and Cancer

The "tubulin code" combines different a/ß-tubulin isotypes with several post-translational modifications (PTMs) to generate microtubule diversity in cells. During cell division, specific microtubule populations in the mitotic spindle are differentially modified, but only recently, the functional significance of the tubulin code, with particular emphasis on the role specified by tubulin PTMs, started to be elucidated. This is the case of a-tubulin detyrosination, which was shown to guide chromosomes during congression to the metaphase plate and allow the discrimination of mitotic errors, whose correction is required to prevent chromosomal instability-a hallmark of human cancers implicated in tumor evolution and metastasis. Although alterations in the expression of certain tubulin isotypes and associated PTMs have been reported in human cancers, it remains unclear whether and how the tubulin code has any functional implications for cancer cell properties. Here, we review the role of the tubulin code in chromosome segregation during mitosis and how it impacts cancer cell properties. In this context, we discuss the existence of an emerging "cancer tubulin code" and the respective implications for diagnostic, prognostic and therapeutic purposes.Danilo Lopes is a student of Programa de Pós-Graduação Ciência para o Desenvolvimento (PGCD) from Instituto Gulbenkian de Ciência (IGC), Oeiras, Portugal and recipient of a studentship (SFRH/BD/135077/2017) from Fundação para a Ciência e a Tecnologia of Portugal. Work in the laboratory of H.M. is funded by the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement No 681443)