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.[6]
Temporal expression patterns and subcellular localization of Aurora kinases in mitotic cells from G2tocytokinesis indicate association with mitotic and meiotic structure.[7] 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.[8]
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).[9]
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.[10]
Expression is typically limited to meiotic cells, but overexpression occurs in some cancer cell lines.[11][12][13][14]PLZF, a transcription repressor, and its CpG island methylation are the most studied modes of regulating AURKC regulation.[15] 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.[9] 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 phosphorylationofhistone H3 and MCAK.[16]
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.[17] 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.[18]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.[16]
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).[19][20] Co-expression of Aurora B and C in vivo interferes with INCENP binding, localization, and stability.[7]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^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. PMID9799611.
^ abSasai 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. PMID15499654.
^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 (1): 143–154. doi:10.2741/e814. PMID28930610.
^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. PMID25990457. S2CID9094864.
Katayama H, Brinkley WR, Sen S (December 2003). "The Aurora kinases: role in cell transformation and tumorigenesis". Cancer and Metastasis Reviews. 22 (4): 451–64. doi:10.1023/A:1023789416385. PMID12884918. S2CID25350728.
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. PMID9809744.
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. PMID15499654.
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. PMID15670791.
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. PMID15917996.
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. PMID15938719. S2CID30043722.
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. PMID16258285. S2CID19776435.
