Abstract
The NIMA-related kinases represent a family of serine/threonine kinases implicated in cell cycle control. The founding member of this family, the NIMA kinase of Aspergillus nidulans, as well as the fission yeast homologue Fin1, contribute to multiple aspects of mitotic progression including the timing of mitotic entry, chromatin condensation, spindle organization and cytokinesis. Mammals contain a large family of eleven NIMA-related kinases, named Nek1 to Nek11. Of these, there is now substantial evidence that Nek2, Nek6, Nek7 and Nek9 also regulate mitotic events. At least three of these kinases, as well as NIMA and Fin1, have been localized to the microtubule organizing centre of their respective species, namely the centrosome or spindle pole body. Here, they have important functions in microtubule organization and mitotic spindle assembly. Other Nek kinases have been proposed to play microtubule-dependent roles in non-dividing cells, most notably in regulating the axonemal microtubules of cilia and flagella. In this review, we discuss the evidence that NIMA-related kinases make a significant contribution to the orchestration of mitotic progression and thereby protect cells from chromosome instability. Furthermore, we highlight their potential as novel chemotherapeutic targets.
Highlights
In 1975, Ron Morris undertook a genetic screen for temperature-sensitive mutants that failed to progress through the cell cycle in the filamentous fungus, Aspergillus nidulans [1]
Homologues of NIMA were not identified in these screens and, when they were eventually identified by sequence comparison, the Kin3 kinase in budding yeast and the Fin1 kinase in fission yeast were confirmed as non-essential genes in these organisms [7,8]
Tantalizing data emerged from the Nurse and Hunter labs in the mid-1990s showing that expression of Aspergillus NIMA in fission yeast or vertebrate cells induced aspects of a premature mitosis, most notably pre
Summary
In 1975, Ron Morris undertook a genetic screen for temperature-sensitive mutants that failed to progress through the cell cycle in the filamentous fungus, Aspergillus nidulans [1]. Overexpression of NIMA in Aspergillus promotes transient formation of mitotic spindle-like structures [5] The reason for this remains elusive, the fact that NIMA and Fin localize to mitotic SPBs suggests a potential role in microtubule nucleation, as well as Cdc2/cyclin B activation [17,26,27]. As HeLa cells treated with Nek or Nek siRNAs or overexpressing catalytically-inactive Nek or Nek show significant numbers of abnormal mitotic spindles, and given the centrosomal localisation of Nek and reduced microtubule nucleating activity of Nek depleted cells, it seems likely that these kinases exert their effects through organisation of the mitotic spindle. With their therapeutic potential in mind, it would appear that NIMA-related kinases are at long last stepping into the limelight
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
