Chromosome Instability & Dynamics Group, i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.
Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.
Cells. 2020 Oct 26;9(11):2356. doi: 10.3390/cells9112356.
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.
“微管蛋白密码”将不同的α/β-微管蛋白同型与几种翻译后修饰（PTM）结合起来，以产生细胞内微管的多样性。在细胞分裂过程中，有丝分裂纺锤体中的特定微管群体被不同程度地修饰，但直到最近，微管蛋白密码的功能意义，特别是强调微管蛋白 PTM 所指定的作用，才开始被阐明。这就是α-微管蛋白去酪氨酸化的情况，它被证明在染色体向中期板聚集的过程中指导染色体，并允许区分有丝分裂错误，需要纠正这些错误以防止染色体不稳定——这是人类癌症的一个标志，与肿瘤进化和转移有关。尽管在人类癌症中已经报道了某些微管蛋白同型和相关 PTM 的表达改变，但尚不清楚微管蛋白密码是否以及如何对癌细胞特性具有任何功能意义。在这里，我们综述了微管蛋白密码在有丝分裂过程中染色体分离中的作用，以及它如何影响癌细胞特性。在这种情况下，我们讨论了新兴的“癌症微管蛋白密码”的存在及其对诊断、预后和治疗目的的相应影响。
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