The serine/threonine kinase Nek6 is required for cell cycle progression through mitosis.
The Aspergillus nidulans protein NIMA (never in mitosis, gene A) is a protein kinase required for the initiation of mitosis, whereas its inactivation is necessary for mitotic exit. Here, we demonstrate that human NIMA-related kinase 6 (Nek6) is required for mitotic progression of human cells. Nek6 is phosphorylated and activated during M phase. Inhibition of Nek6 function by either overexpression of an inactive Nek6 mutant or elimination of endogenous Nek6 by siRNA arrests cells in M phase and triggers apoptosis. Time-lapse recording of the cell cycle progression of cells expressing kinase-inactive Nek6 reveals mitotic arrest at the metaphase stage prior to cells entering apoptosis. In contrast to NIMA and the closely related mammalian Nek2 kinase, which regulate centrosome function and separation, our data demonstrate an important function for Nek6 during mitosis and suggest that Nek6 kinase is required for metaphase-anaphase transition.
Yin
Min-Jean
MJ
SUGEN, Inc., South San Francisco, California 94080-4811, USA. min-jean.yin@pfizer.com
Shao
Lihua
L
Voehringer
David
D
Smeal
Tod
T
Jallal
Bahija
B
D000705:Anaphase; D017209:Apoptosis; D002453:Cell Cycle; D002460:Cell Line; D002469:Cell Separation; D018385:Centrosome / Q000378:metabolism; D005434:Flow Cytometry; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D008677:Metaphase; D008853:Microscopy; D008938:Mitosis; D000072379:NIMA-Related Kinases; D010455:Peptides / Q000737:chemistry; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
D010455:Peptides; D034741:RNA, Small Interfering; C459456:NEK6 protein, human; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases