Hec1/Ndc80 Tail Domain Function at the Kinetochore-Microtubule Interface

Abstract

Successful mitotic cell division is critically dependent on the formation of correct attachments between chromosomes and spindle microtubules. Microtubule attachments are mediated by kinetochores, which are large proteinaceous structures assembled on centromeric chromatin of mitotic chromosomes. These attachments must be sufficiently stable to transduce force; however, the strength of these attachments are also tightly regulated to ensure timely, error-free progression through mitosis. The highly conserved, kinetochore-associated NDC80 complex is a core component of the kinetochore-microtubule attachment machinery in eukaryotic cells. A small, disordered region within the Hec1 subunit of the NDC80 complex-the N-terminal "tail" domain-has been actively investigated during the last decade due to its roles in generating and regulating kinetochore-microtubule attachments. In this review, we discuss the role of the NDC80 complex, and specifically the Hec1 tail domain, at the kinetochore-microtubule interface, and how recent studies provide a more unified view of Hec1 tail domain function.

BUB1 and CENP-U, Primed by CDK1, Are the Main PLK1 Kinetochore Receptors in Mitosis

“…We cannot exclude the possibility that PLK1 recruitment to BUB1 and CENP-U activates downstream phosphorylation events that promote hierarchical recruitment of PLK1 to additional receptors, thus explaining the plethora of different potential PLK1 kinetochore receptors previously identified (see Introduction ). Because our PLK1 localization experiments were performed in nocodazole, i.e., in the absence of microtubules, they do not exclude recruitment of PLK1 to additional receptors generated after recruitment of “late” kinetochore residents, such as the SKA and SKAP complexes ( Wimbish and DeLuca, 2020 ).…”

The Hec1/Ndc80 tail domain is required for force generation at kinetochores, but is dispensable for kinetochore–microtubule attachment formation and Ska complex recruitment

“…, 2017 ). The Hec1 protein contains an N-terminal, unstructured “tail” domain that has also been implicated in forming kinetochore–microtubule attachments in cells, although the requirement for the tail domain in this process varies among eukaryotic species ( Wimbish and DeLuca, 2020 ). The Hec1 tail domain in Saccharomyces cerevisiae and Caenorhabditis elegans is dispensable for formation of stable kinetochore–microtubule attachments ( Kemmler et al.…”

Identification of APEX2 as an oncogene in liver cancer

“…The positive and negative correlated genes were represented. Furthermore, the results of cellular component module of GO Ontology suggested that APEX2 was closely associated with the kinetochore and spindle microtubule (Figure 4B ), two main cellular components involved in cell proliferation[ 23 ]. The significant enrichment score suggested that APEX2 may be involved in the positive regulation of liver cancer cell proliferation.…”