NEK6 explained

Serine/threonine-protein kinase Nek6 is an enzyme that in humans is encoded by the NEK6 gene.^{[1] [2]}

Function

The Aspergillus nidulans 'never in mitosis A' (NIMA) gene encodes a serine/threonine kinase that controls initiation of mitosis. NIMA-related kinases (NEKs) are a group of protein kinases that are homologous to NIMA. Evidence suggests that NEKs perform functions similar to those of NIMA.^[2]

It is a protein kinase which plays an important role in mitotic cell cycle progression. Required for chromosome segregation at metaphase-anaphase transition, robust mitotic spindle formation and cytokinesis. Phosphorylates ATF4, CIR1, PTN, RAD26L, RBBP6, RPS7, RPS6KB1, TRIP4, STAT3 and histones H1 and H3. Phosphorylates KIF11 to promote mitotic spindle formation. Involved in G2/M phase cell cycle arrest induced by DNA damage. Inhibition of activity results in apoptosis. May contribute to tumorigenesis by suppressing p53/TP53-induced cancer cell senescence.

Interactions

NEK6 has been shown to interact with NEK9.^{[3] [4] [5]}

Further reading

• Kobayashi T, Cohen P . Activation of serum- and glucocorticoid-regulated protein kinase by agonists that activate phosphatidylinositide 3-kinase is mediated by 3-phosphoinositide-dependent protein kinase-1 (PDK1) and PDK2 . Biochem. J. . 339 (Pt 2) . 2 . 319–28 . 1999 . 10191262 . 1220160 . 10.1042/0264-6021:3390319 .
• Kandli M, Feige E, Chen A, Kilfin G, Motro B . Isolation and characterization of two evolutionarily conserved murine kinases (Nek6 and nek7) related to the fungal mitotic regulator, NIMA . Genomics . 68 . 2 . 187–96 . 2001 . 10964517 . 10.1006/geno.2000.6293 .
• Belham C, Comb MJ, Avruch J . Identification of the NIMA family kinases NEK6/7 as regulators of the p70 ribosomal S6 kinase . Curr. Biol. . 11 . 15 . 1155–67 . 2001 . 11516946 . 10.1016/S0960-9822(01)00369-4 . 15509230 . free . 2001CBio...11.1155B .
• Kimura M, Okano Y . Identification and assignment of the human NIMA-related protein kinase 7 gene (NEK7) to human chromosome 1q31.3 . Cytogenet. Cell Genet. . 94 . 1–2 . 33–8 . 2001 . 11701951 . 10.1159/000048779 . 27666742 .
• Lizcano JM, Deak M, Morrice N, Kieloch A, Hastie CJ, Dong L, Schutkowski M, Reimer U, Alessi DR . Molecular basis for the substrate specificity of NIMA-related kinase-6 (NEK6). Evidence that NEK6 does not phosphorylate the hydrophobic motif of ribosomal S6 protein kinase and serum- and glucocorticoid-induced protein kinase in vivo . J. Biol. Chem. . 277 . 31 . 27839–49 . 2002 . 12023960 . 10.1074/jbc.M202042200 . free .
• Hashimoto Y, Akita H, Hibino M, Kohri K, Nakanishi M . Identification and characterization of Nek6 protein kinase, a potential human homolog of NIMA histone H3 kinase . Biochem. Biophys. Res. Commun. . 293 . 2 . 753–8 . 2002 . 12054534 . 10.1016/S0006-291X(02)00297-8 .
• Roig J, Mikhailov A, Belham C, Avruch J . Nercc1, a mammalian NIMA-family kinase, binds the Ran GTPase and regulates mitotic progression . Genes Dev. . 16 . 13 . 1640–58 . 2002 . 12101123 . 186374 . 10.1101/gad.972202 .
• Matsuda A, Suzuki Y, Honda G, Muramatsu S, Matsuzaki O, Nagano Y, Doi T, Shimotohno K, Harada T, Nishida E, Hayashi H, Sugano S . Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways . Oncogene . 22 . 21 . 3307–18 . 2003 . 12761501 . 10.1038/sj.onc.1206406 . 38880905 .
• Belham C, Roig J, Caldwell JA, Aoyama Y, Kemp BE, Comb M, Avruch J . A mitotic cascade of NIMA family kinases. Nercc1/Nek9 activates the Nek6 and Nek7 kinases . J. Biol. Chem. . 278 . 37 . 34897–909 . 2003 . 12840024 . 10.1074/jbc.M303663200 . free .
• Yin MJ, Shao L, Voehringer D, Smeal T, Jallal B . The serine/threonine kinase Nek6 is required for cell cycle progression through mitosis . J. Biol. Chem. . 278 . 52 . 52454–60 . 2004 . 14563848 . 10.1074/jbc.M308080200 . free .
• Barrios-Rodiles M, Brown KR, Ozdamar B, Bose R, Liu Z, Donovan RS, Shinjo F, Liu Y, Dembowy J, Taylor IW, Luga V, Przulj N, Robinson M, Suzuki H, Hayashizaki Y, Jurisica I, Wrana JL . High-throughput mapping of a dynamic signaling network in mammalian cells . Science . 307 . 5715 . 1621–5 . 2005 . 15761153 . 10.1126/science.1105776 . 2005Sci...307.1621B . 39457788 .
• Chen J, Li L, Zhang Y, Yang H, Wei Y, Zhang L, Liu X, Yu L . Interaction of Pin1 with Nek6 and characterization of their expression correlation in Chinese hepatocellular carcinoma patients . Biochem. Biophys. Res. Commun. . 341 . 4 . 1059–65 . 2006 . 16476580 . 10.1016/j.bbrc.2005.12.228 .
• Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D . Large-scale mapping of human protein-protein interactions by mass spectrometry . Mol. Syst. Biol. . 3 . 1 . 89 . 2007 . 17353931 . 1847948 . 10.1038/msb4100134 .
• Lee EJ, Hyun SH, Chun J, Kang SS . Human NIMA-related kinase 6 is one of the Fe65 WW domain binding proteins . Biochem. Biophys. Res. Commun. . 358 . 3 . 783–8 . 2007 . 17512906 . 10.1016/j.bbrc.2007.04.203 .

Notes and References

1. Li MZ, Yu L, Liu Q, Chu JY, Zhao SY . Assignment of NEK6, a NIMA-related gene, to human chromosome 9q33. 3→q34.11 by radiation hybrid mapping . Cytogenet Cell Genet . 87 . 3–4 . 271–2 . April 2000 . 10702691 . 10.1159/000015445 . 46463586 .
2. Web site: Entrez Gene: NEK6 NIMA (never in mitosis gene a)-related kinase 6.
3. Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D . Large-scale mapping of human protein-protein interactions by mass spectrometry . Mol. Syst. Biol. . 3 . 1 . 89 . 2007 . 17353931 . 1847948 . 10.1038/msb4100134 .
4. Belham C, Roig J, Caldwell JA, Aoyama Y, Kemp BE, Comb M, Avruch J . A mitotic cascade of NIMA family kinases. Nercc1/Nek9 activates the Nek6 and Nek7 kinases . J. Biol. Chem. . 278 . 37 . 34897–909 . September 2003 . 12840024 . 10.1074/jbc.M303663200 . free .
5. Roig J, Mikhailov A, Belham C, Avruch J . Nercc1, a mammalian NIMA-family kinase, binds the Ran GTPase and regulates mitotic progression . Genes Dev. . 16 . 13 . 1640–58 . July 2002 . 12101123 . 186374 . 10.1101/gad.972202 .