AURKC

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Identifiers
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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
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Serine/threonine-protein kinase 13 is an enzyme that in humans is encoded by the AURKC gene.[1][2]

Function

This gene encodes a member of the highly conserved Aurora subfamily of serine/threonine protein kinases with two other members, Aurora A and Aurora B. The encoded protein is a chromosomal passenger protein that forms complexes with Aurora-B and inner centromere proteins and may play a role in organizing microtubules in relation to centrosome/spindle function during mitosis. This gene is overexpressed in several cancer cell lines, suggesting an involvement in oncogenic signal transduction. Alternative splicing results in multiple transcript variants.[2]

Function

Temporal expression patterns and subcellular localization of Aurora kinases in mitotic cells from G2 to cytokinesis indicate association with mitotic and meiotic structure.[3] Although yeast contain only one Aurora kinase and C. elegans and Drosophila contain only two, mammals have three Aurora kinases with 67-76% homology that are structurally similar and localize similarly.[4]

Aurora C localizes to the centrosome and then to the midzone of mitotic cells from anaphase to cytokinesis. It is expressed about an order of magnitude less than Aurora B in diploid human fibroblasts, with mRNA and protein concentrations peaking during the G2/M phase. Aurora C levels, however, peak after those of Aurora B later in the M phase. While Aurora A and B are expressed in mitotic somatic cells, Aurora C is more often expressed during meiosis (spermatogenesis and oogenesis).[5]

Aurora B kinase regulates kinetochore maturation, destabilization of improper kinetochore-microtubule attachments, and spindle assembly checkpoint (SAC), central spindle organization, and cytokinesis. Aneuploidy results from independent and simultaneous inhibition of Aurora B and Aurora C. Slattery et al. found that they have overlapping functions and that Aurora C was able to rescue Aurora B-deficient mitotic cells from aneuploidy.[6]

Clinical Significance

Expression is typically limited to meiotic cells, but overexpression occurs in some cancer cell lines.[7][8][9][10][11] PLZF, a transcription repressor, and its CpG island methylation are the most studied modes of regulating AURKC regulation.[12] Although all of the Aurora kinases are overexpressed in many cancer cell lines, only Aurora A and C possess oncogenic activity, producing multinucleated cells and tumors in vivo when overexpressed.[5] When cells overexpressing Aurora C were treated with nocodazole to turn on the SAC, Aurora B protein stability and activity decreased. This then prevented activation of SAC protein BubR1 and phosphorylation of histone H3 and MCAK.[13]

Inactivating mutations of Aurora C have been shown to cause infertility in men characterized by macrocephalic and multiflagellular spermatozoa. Homozygous and heterozygous c.144delC mutation in the AURKC gene was found with an allelic frequency of 2.14% in Moroccan men with unexplained spermatogenic failure. The heterozygous state had a frequency of 1% in normospermic fertile men.[14] Although c.144delC represents 85.5% of mutant alleles, the nonsense mutation p.Y248* (13% of all mutant alleles) is present in both European and African men and can lead to infertility.[15] Klinefelter syndrome and Y chromosome microdeletion analyses are the most common genetic tests offered to infertile men, but AURKC and DPY19L2 defects are the leading cause of infertility in North African men.[13]

Interactions

Both Aurora B and C interact with the inner centromere protein (INCENP) from the C-terminal to the conserved IN box domain, but Aurora B preferentially binds INCENP. The chromosomal passenger complex (CPC), essential for chromosome segregation, contains the four subunits: the Aurora kinase, INCENP, survivin, and borealin (also known as dasra).[16][17] Co-expression of Aurora B and C in vivo interferes with INCENP binding, localization, and stability.[3]

References

  1. ↑ Bernard M, Sanseau P, Henry C, Couturier A, Prigent C (November 1998). "Cloning of STK13, a third human protein kinase related to Drosophila aurora and budding yeast Ipl1 that maps on chromosome 19q13.3-ter". Genomics. 53 (3): 406–9. doi:10.1006/geno.1998.5522. PMID 9799611.
  2. ↑ 2.0 2.1 "Entrez Gene: AURKC aurora kinase C".
  3. ↑ 3.0 3.1 Sasai K, Katayama H, Stenoien DL, Fujii S, Honda R, Kimura M, Okano Y, Tatsuka M, Suzuki F, Nigg EA, Earnshaw WC, Brinkley WR, Sen S (December 2004). "Aurora-C kinase is a novel chromosomal passenger protein that can complement Aurora-B kinase function in mitotic cells". Cell Motility and the Cytoskeleton. 59 (4): 249–63. doi:10.1002/cm.20039. PMID 15499654.
  4. ↑ Crosio C, Fimia GM, Loury R, Kimura M, Okano Y, Zhou H, Sen S, Allis CD, Sassone-Corsi P (February 2002). "Mitotic phosphorylation of histone H3: spatio-temporal regulation by mammalian Aurora kinases". Molecular and Cellular Biology. 22 (3): 874–85. doi:10.1128/MCB.22.3.874-885.2002. PMC 133550. PMID 11784863.
  5. ↑ 5.0 5.1 Khan J, Ezan F, Crémet JY, Fautrel A, Gilot D, Lambert M, Benaud C, Troadec MB, Prigent C (2011). "Overexpression of active Aurora-C kinase results in cell transformation and tumour formation". PLOS One. 6 (10): e26512. doi:10.1371/journal.pone.0026512. PMID 22046298. Retrieved 30 Jun 2018.
  6. ↑ Slattery SD, Mancini MA, Brinkley BR, Hall RM (September 2009). "Aurora-C kinase supports mitotic progression in the absence of Aurora-B". Cell Cycle. 8 (18): 2984–94. doi:10.4161/cc.8.18.9591. PMID 19713763.
  7. ↑ "Aurora C Kinase" (PDF). www.cellsignal.com. Cell Signaling Technology. 2008. Retrieved 30 Jun 2018.
  8. ↑ Mobasheri MB, Shirkoohi R, Zendehdel K, Jahanzad I, Talebi S, Afsharpad M, Modarressi MH (September 2015). "Transcriptome analysis of the cancer/testis genes, DAZ1, AURKC, and TEX101, in breast tumors and six breast cancer cell lines". Tumour Biology. 36 (10): 8201–6. doi:10.1007/s13277-015-3546-4. PMID 25994570.
  9. ↑ Tsou JH, Chang KC, Chang-Liao PY, Yang ST, Lee CT, Chen YP, Lee YC, Lin BW, Lee JC, Shen MR, Chuang CK, Chang WC, Wang JM, Hung LY (October 2011). "Aberrantly expressed AURKC enhances the transformation and tumourigenicity of epithelial cells". The Journal of Pathology. 225 (2): 243–54. doi:10.1002/path.2934. PMID 21710690.
  10. ↑ Nna E, Madukwe J, Egbujo E, Obiorah C, Okolie C, Echejoh G, Yahaya A, Adisa J, Uzoma I (2013). "Gene expression of Aurora kinases in prostate cancer and nodular hyperplasia tissues". Medical Principles and Practice. 22 (2): 138–43. doi:10.1159/000342679. PMID 23075505.
  11. ↑ Pereira HS, Soares Lima SC, de Faria PS, Cardoso LC, Seuanez HN (January 2018). "AURKC promoter regions are differentially methylated in Wilms' tumor". Frontiers in Bioscience. 10: 143–154. PMID 28930610.
  12. ↑ Fujii S, Srivastava V, Hegde A, Kondo Y, Shen L, Hoshino K, Gonzalez Y, Wang J, Sasai K, Ma X, Katayama H, Estecio MR, Hamilton SR, Wistuba I, Issa JP, Sen S (September 2015). "Regulation of AURKC expression by CpG island methylation in human cancer cells". Tumour Biology. 36 (10): 8147–58. doi:10.1007/s13277-015-3553-5. PMID 25990457.
  13. ↑ 13.0 13.1 Lin BW, Wang YC, Chang-Liao PY, Lin YJ, Yang ST, Tsou JH, Chang KC, Liu YW, Tseng JT, Lee CT, Lee JC, Hung LY (March 2014). "Overexpression of Aurora-C interferes with the spindle checkpoint by promoting the degradation of Aurora-B". Cell Death & Disease. 5: e1106. doi:10.1038/cddis.2014.37. PMID 24603334.
  14. ↑ Eloualid A, Rouba H, Rhaissi H, Barakat A, Louanjli N, Bashamboo A, McElreavey K (April 2014). "Prevalence of the Aurora kinase C c.144delC mutation in infertile Moroccan men". Fertility and Sterility. 101 (4): 1086–90. doi:10.1016/j.fertnstert.2013.12.040. PMID 24484996.
  15. ↑ Ben Khelifa M, Coutton C, Blum MG, Abada F, Harbuz R, Zouari R, Guichet A, May-Panloup P, Mitchell V, Rollet J, Triki C, Merdassi G, Vialard F, Koscinski I, Viville S, Keskes L, Soulie JP, Rives N, Dorphin B, Lestrade F, Hesters L, Poirot C, Benzacken B, Jouk PS, Satre V, Hennebicq S, Arnoult C, Lunardi J, Ray PF (November 2012). "Identification of a new recurrent aurora kinase C mutation in both European and African men with macrozoospermia". Human Reproduction. 27 (11): 3337–46. doi:10.1093/humrep/des296. PMID 22888167.
  16. ↑ Carmena M, Wheelock M, Funabiki H, Earnshaw WC (December 2012). "The chromosomal passenger complex (CPC): from easy rider to the godfather of mitosis". Nature Reviews. Molecular Cell Biology. 13 (12): 789–803. doi:10.1038/nrm3474. PMC 3729939. PMID 23175282.
  17. ↑ Fernández-Miranda G, Trakala M, Martín J, Escobar B, González A, Ghyselinck NB, Ortega S, Cañamero M, Pérez de Castro I, Malumbres M (July 2011). "Genetic disruption of aurora B uncovers an essential role for aurora C during early mammalian development". Development. 138 (13): 2661–72. doi:10.1242/dev.066381. PMID 21613325.

Further reading

  • Katayama H, Brinkley WR, Sen S (December 2003). "The Aurora kinases: role in cell transformation and tumorigenesis". Cancer Metastasis Reviews. 22 (4): 451–64. doi:10.1023/A:1023789416385. PMID 12884918.
  • Tseng TC, Chen SH, Hsu YP, Tang TK (October 1998). "Protein kinase profile of sperm and eggs: cloning and characterization of two novel testis-specific protein kinases (AIE1, AIE2) related to yeast and fly chromosome segregation regulators". DNA and Cell Biology. 17 (10): 823–33. doi:10.1089/dna.1998.17.823. PMID 9809744.
  • Kimura M, Matsuda Y, Yoshioka T, Okano Y (March 1999). "Cell cycle-dependent expression and centrosome localization of a third human aurora/Ipl1-related protein kinase, AIK3". The Journal of Biological Chemistry. 274 (11): 7334–40. doi:10.1074/jbc.274.11.7334. PMID 10066797.
  • Clark AG, Glanowski S, Nielsen R, Thomas PD, Kejariwal A, Todd MA, Tanenbaum DM, Civello D, Lu F, Murphy B, Ferriera S, Wang G, Zheng X, White TJ, Sninsky JJ, Adams MD, Cargill M (December 2003). "Inferring nonneutral evolution from human-chimp-mouse orthologous gene trios". Science. 302 (5652): 1960–3. doi:10.1126/science.1088821. PMID 14671302.
  • Li X, Sakashita G, Matsuzaki H, Sugimoto K, Kimura K, Hanaoka F, Taniguchi H, Furukawa K, Urano T (November 2004). "Direct association with inner centromere protein (INCENP) activates the novel chromosomal passenger protein, Aurora-C". The Journal of Biological Chemistry. 279 (45): 47201–11. doi:10.1074/jbc.M403029200. PMID 15316025.
  • Sasai K, Katayama H, Stenoien DL, Fujii S, Honda R, Kimura M, Okano Y, Tatsuka M, Suzuki F, Nigg EA, Earnshaw WC, Brinkley WR, Sen S (December 2004). "Aurora-C kinase is a novel chromosomal passenger protein that can complement Aurora-B kinase function in mitotic cells". Cell Motility and the Cytoskeleton. 59 (4): 249–63. doi:10.1002/cm.20039. PMID 15499654.
  • Yan X, Wu Y, Li Q, Cao L, Liu X, Saiyin H, Yu L (March 2005). "Cloning and characterization of a novel human Aurora C splicing variant". Biochemical and Biophysical Research Communications. 328 (1): 353–61. doi:10.1016/j.bbrc.2004.12.168. PMID 15670791.
  • Chen HL, Tang CJ, Chen CY, Tang TK (2005). "Overexpression of an Aurora-C kinase-deficient mutant disrupts the Aurora-B/INCENP complex and induces polyploidy". Journal of Biomedical Science. 12 (2): 297–310. doi:10.1007/s11373-005-0980-0. PMID 15917996.
  • Yan X, Cao L, Li Q, Wu Y, Zhang H, Saiyin H, Liu X, Zhang X, Shi Q, Yu L (June 2005). "Aurora C is directly associated with Survivin and required for cytokinesis". Genes to Cells. 10 (6): 617–26. doi:10.1111/j.1365-2443.2005.00863.x. PMID 15938719.
  • Dutertre S, Hamard-Péron E, Cremet JY, Thomas Y, Prigent C (December 2005). "The absence of p53 aggravates polyploidy and centrosome number abnormality induced by Aurora-C overexpression". Cell Cycle. 4 (12): 1783–7. doi:10.4161/cc.4.12.2172. PMID 16258285.
  • Dieterich K, Soto Rifo R, Faure AK, Hennebicq S, Ben Amar B, Zahi M, Perrin J, Martinez D, Sèle B, Jouk PS, Ohlmann T, Rousseaux S, Lunardi J, Ray PF (May 2007). "Homozygous mutation of AURKC yields large-headed polyploid spermatozoa and causes male infertility". Nature Genetics. 39 (5): 661–5. doi:10.1038/ng2027. PMID 17435757.

External links

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