Abstract
The “tubulin code” combines different α/β-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 α-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.
Highlights
Cell Division Group, Experimental Biology Unit, Department of Biomedicine, Faculdade de Medicina, Universidade do Porto, Alameda Prof
As α/β-tubulin heterodimers polymerize into microtubules, the combination of isotype expression with post-translational modifications (PTMs) generate microtubule diversity or a “tubulin code” (Figure 1), which has been implicated in the regulation of microtubule properties and functions underlying fundamental cellular processes [4,5]
Mitosis relies on the critical contribution of microtubules, as well as several microtubule-associated proteins (MAPs) and motors, to regulate several key mechanisms underlying the faithful segregation of the genetic material during cell division
Summary
Microtubules are dynamic, hollow cylindrical structures typically formed by thirteen laterally associated protofilaments of α/β-tubulin heterodimers that interact head-to-tail [1]. α- and β-tubulin proteins are encoded by several different genes ( known as tubulin isotypes) that diverge in their. Acetylation, detyrosination, polyglutamylation and polyglycylation are amongst the best characterized tubulin PTMs (Figure 1). Cells 2020, 9, x FOR PEER REVIEW by tubulin carboxypeptidases (TCPs), including the recently identified Vasohibin 1 (VASH1) and catalytic removal of the last tyrosine present at the C-terminal tail of most isoforms by tubulin. O-GlcNAcylation [33] occur in polyamination, the tubulin corephosphorylation, structure adjacent ubiquitinylation, sumoylation, palmitoylation (reviewed in [5]) and O-GlcNAcylation [33] occur in to the C-terminal tails. These PTMs remain poorly characterized at the functional level but are likely to the tubulin core structure adjacent to the C-terminal tails.
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