MAPping the Ndc80 loop in cancer: A possible link between Ndc80/Hec1 overproduction and cancer formation

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.

Keywords: Kinesin-8; Ndc80/Hec1; TACC; cancer; ch-TOG; loop; overexpression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carcinogenesis / metabolism
  • Cytoskeletal Proteins
  • Gene Expression
  • Humans
  • Microtubule-Associated Proteins / metabolism*
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Protein Interaction Domains and Motifs
  • Protein Interaction Maps


  • Cytoskeletal Proteins
  • Microtubule-Associated Proteins
  • NDC80 protein, human
  • Nuclear Proteins