Identification and characterization of Nek6 protein kinase, a potential human homolog of NIMA histone H3 kinase.
In Aspergillus nidulans, the kinase activity of NIMA (never in mitosis, gene A) is critical for the initiation of mitosis. NIMA regulates mitotic chromatin condensation through phosphorylation of histone H3 at serine 10. In the present study, we identified human Nek6 (hNek6), a member of the mammalian NIMA-related kinases. The predicted hNek6 protein is comprised of 338 amino acids. Northern blot analysis revealed that hNek6 transcripts are ubiquitously expressed with the highest expression found in the heart and skeletal muscle. Lower cell cycle-dependent expression of hNek6 transcripts was observed in the early G1 phase. GFP-fused hNek6 protein showed both nuclear and cytoplasmic localizations in HeLa cells. Fluorescence in situ hybridization using full-length hNek6 cDNA as a probe showed that the hNek6 gene is localized to human chromosome 9q33-34, a region at which the loss of heterozygosity is associated with transitional cell carcinomas. Importantly, recombinant hNek6 protein produced in insect cells effectively phosphorylated histones H1 and H3, but not casein. Thus, these results suggest that, unlike other mammalian NIMA-related kinases, Nek6 is a mitotic histone kinase which regulates chromatin condensation in mammalian cells.
Hashimoto
Yoshihiro
Y
Department of Biochemistry, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Akita
Hidetoshi
H
Hibino
Mitsunobu
M
Kohri
Kenjiro
K
Nakanishi
Makoto
M
D000595:Amino Acid Sequence; D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000201:enzymology; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D000072380:NIMA-Related Kinase 1; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D016415:Sequence Alignment; D014018:Tissue Distribution
D018797:Cell Cycle Proteins; D006657:Histones; D012333:RNA, Messenger; C000606914:NEK1 protein, human; C459456:NEK6 protein, human; D000072380:NIMA-Related Kinase 1; D000072379:NIMA-Related Kinases; C442331:NIMA-related kinase 6; C000606920:Nek1 protein, mouse; D017346:Protein Serine-Threonine Kinases