Tang Ngang Heok, Toda Takashi
Laboratory of Cell Regulation, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, London, UK.
Bioessays. 2015 Mar;37(3):248-56. doi: 10.1002/bies.201400175. Epub 2015 Jan 2.
Mis-regulation (e.g. overproduction) of the human Ndc80/Hec1 outer kinetochore protein has been associated with aneuploidy and tumourigenesis, but the genetic basis and underlying mechanisms of this phenomenon remain poorly understood. Recent studies have identified the ubiquitous Ndc80 internal loop as a protein-protein interaction platform. Binding partners include the Ska complex, the replication licensing factor Cdt1, the Dam1 complex, TACC-TOG microtubule-associated proteins (MAPs) and kinesin motors. We review the field and propose that the overproduction of Ndc80 may unfavourably absorb these interactors through the internal loop domain and lead to a change in the equilibrium of MAPs and motors in the cells. This sequestration will disrupt microtubule dynamics and the proper segregation of chromosomes in mitosis, leading to aneuploid formation. Further investigation of Ndc80 internal loop-MAPs interactions will bring new insights into their roles in kinetochore-microtubule attachment and tumourigenesis.
人类着丝粒外层Ndc80/Hec1蛋白的失调（如过度产生）与非整倍体和肿瘤发生有关，但这种现象的遗传基础和潜在机制仍知之甚少。最近的研究已确定普遍存在的Ndc80内环是一个蛋白质-蛋白质相互作用平台。其结合伙伴包括Ska复合体、复制许可因子Cdt1、Dam1复合体、TACC-TOG微管相关蛋白（MAPs）和驱动蛋白马达。我们综述了该领域，并提出Ndc80的过度产生可能通过内环结构域不利地吸收这些相互作用蛋白，并导致细胞中MAPs和马达平衡的改变。这种隔离将破坏微管动力学和有丝分裂中染色体的正确分离，导致非整倍体形成。对Ndc80内环-MAPs相互作用的进一步研究将为它们在着丝粒-微管附着和肿瘤发生中的作用带来新的见解。
