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Nek2A kinase stimulates centrosome disjunction and is required for formation of bipolar mitotic spindles.

By Alison J. Faragher and Andrew M. Fry


Nek2A is a cell cycle-regulated kinase of the never in mitosis A (NIMA) family that is highly enriched at the centrosome. One model for Nek2A function proposes that it regulates cohesion between the mother and daughter centriole through phosphorylation of C-Nap1, a large coiled-coil protein that localizes to centriolar ends. Phosphorylation of C-Nap1 at the G2/M transition may trigger its displacement from centrioles, promoting their separation and subsequent bipolar spindle formation. To test this model, we generated tetracycline-inducible cell lines overexpressing wild-type and kinase-dead versions of Nek2A. Live cell imaging revealed that active Nek2A stimulates the sustained splitting of interphase centrioles indicative of loss of cohesion. However, this splitting is accompanied by only a partial reduction in centriolar C-Nap1. Strikingly, induction of kinase-dead Nek2A led to formation of monopolar spindles with unseparated spindle poles that lack C-Nap1. Furthermore, kinase-dead Nek2A interfered with chromosome segregation and cytokinesis and led to an overall change in the DNA content of the cell population. These results provide the first direct evidence in human cells that Nek2A function is required for the correct execution of mitosis, most likely through promotion of centrosome disjunction. However, they suggest that loss of centriole cohesion and C-Nap1 displacement may be distinct mitotic events.Peer-reviewedPublisher Versio

Publisher: American society for cell biology
Year: 2003
DOI identifier: 10.1091/mbc.E03-02-0108
OAI identifier:

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  2. (1998). A centrosomal function for the human Nek2 protein kinase, a member of the NIMAfamily of cell cycle regulators. doi
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  4. (2002). Alternative splice variants of the human centrosomal kinase Nek2 exhibit distinct patterns of expression in mitosis. doi
  5. (1996). Antibody microinjection reveals an essential role for human polo-like kinase 1 (Plk1) in the functional maturation of mitotic centrosomes. doi
  6. (2001). APC/C-mediated destruction of the centrosomal kinase Nek2A occurs in early mitosis and depends upon a cyclin A-type D-box. doi
  7. (2002). Aurora-A overexpression reveals tetraploidization as a major route to centrosome amplification in p53/ cells. doi
  8. (1998). Autoantibodies to a group of centrosomal proteins in human autoimmune sera reactive with the centrosome. doi
  9. (2000). Basal bodies and centrioles: their function and structure. doi
  10. (1998). C-Nap1, a novel centrosomal coiled-coil protein and candidate substrate of the cell cycle-regulated protein kinase Nek2. doi
  11. (1995). Cell cycle regulation of the activity and subcellular localization of PLK1, a human protein kinase implicated in mitotic spindle function. doi
  12. (2001). Centrioles take center stage. doi
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  14. (2001). Centrosome cohesion is regulated by a balance of kinase and phosphatase activities.
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  16. (1998). Centrosome hypertrophy in human breast tumors: implications for genomic stability and cell polarity. doi
  17. (1992). Centrosome organization and centriole architecture: their sensitivity to divalent cations. doi
  18. (2001). Centrosome-dependent exit of cytokinesis in animal cells. doi
  19. (1999). Cyclin-dependent kinase control of centrosome duplication. doi
  20. (2002). Deregulated human Cdc14A phosphatase disrupts centrosome separation and chromosome segregation. doi
  21. (1999). Direct interaction of pericentrin with cytoplasmic dynein light intermediate chain contributes to mitotic spindle organization. doi
  22. (2002). Expression analysis of pediatric solid tumor cell lines using oligonucleotide microarrays. doi
  23. (1998). Glutamylation of centriole and cytoplasmic tubulin in proliferating non-neuronal cells. doi
  24. (2001). Identification of centrosome kinases. doi
  25. (2002). Inhibitor-2 regulates protein phosphatase-1 complexed with NimA-related kinase to induce centrosome separation. doi
  26. (2001). It takes two to tangoā€¯: understanding how centrosome duplication is regulated throughout the cell cycle. doi
  27. (2001). Mitotic kinases as regulators of cell division and its checkpoints.
  28. (1995). Molecular Biology of the Cell2888
  29. (2002). Nek2 localizes to multiple sites in mitotic cells, suggesting its involvement in multiple cellular functions during the cell cycle. doi
  30. (2000). Nek2B, a novel maternal form of Nek2 kinase, is essential for the assembly or maintenance of centrosomes in early Xenopus embryos. doi
  31. (2000). NIMA-related kinase 2 (Nek2), a cell cycle-regulated protein kinase localized to centrosomes, is complexed to protein phosphatase 1. doi
  32. (2000). Probing spindle assembly mechanisms with monastrol, a small molecule inhibitor of the mitotic kinesin, doi
  33. (1990). Production and characterization of monoclonal antibodies to the mammalian sperm cytoskeleton. doi
  34. (1999). Protein kinases in control of the centrosome cycle. doi
  35. (2001). Re-evaluating centrosome function.
  36. (1987). Structural and chemical characterization of isolated centrosomes. doi
  37. (1999). Studying the composition and function of centrosomes in vertebrates. doi
  38. (2000). The centrosomal protein C-Nap1 displays properties supporting a role in cell cycle-regulated centrosome cohesion. doi
  39. (2002). The centrosome cycle. doi
  40. (2002). The mechanism regulating dissociation of the centrosomal protein CNap1 from mitotic spindle poles.
  41. (2002). The Nek2 protein kinase: a novel regulator of centrosome structure. doi
  42. (2000). The NIMA-related kinase X-Nek2B is required for efficient assembly of the zygotic centrosome in Xenopus laevis. doi
  43. (2000). The respective contributions of the mother and daughter centrioles to centrosome activity and behaviour in vertebrate cells. doi
  44. (2002). The Rho-associated protein kinase p160ROCK is required for centrosome positioning. doi
  45. (1999). The sudden recruitment of -tubulin to the centrosome at the onset of mitosis and its dynamic exchange throughout the cell cycle, do not require microtubules. doi

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