Disease relevance of AURKC

• Similar modifications, at the mRNA level, could be observed in 7 papillary carcinoma tissues for Aurora-A and B, but not for Aurora-C [1].
• We conclude that the absence of AURKC causes male infertility owing to the production of large-headed multiflagellar polyploid spermatozoa [2].

High impact information on AURKC

• Interestingly, all of the identified Aurora-A substrates were resistant to serve as substrates for Aurora-B or Aurora-C, suggesting that these Aurora family members may have distinct substrate specificity for propagation of diverse signaling pathways, even though they share a conserved catalytic kinase domain [3].
• Human Aurora kinases have three gene family members: Aurora-A, Aurora-B, and Aurora-C [3].
• We show that INCENP binds and activates Aurora-C in vivo and in vitro [4].
• Furthermore, Aurora-C co-expressed with INCENP elicits the phosphorylation of endogenous histone H3 in mammalian cells, even though this phosphorylation is not sufficient to establish chromosome condensation in interphase cells [4].
• The zinc finger domain of Tzfp binds to the tbs motif located at the upstream flanking region of the Aie1 (aurora-C) kinase gene [5].

Biological context of AURKC

• We therefore suggest that Aurora-C is a novel chromosomal passenger protein that cooperates with Aurora-B to regulate mitotic chromosome dynamics in mammalian cells [4].
• We present evidence that Aurora-C, like Aurora-B kinase, is a chromosomal passenger protein localizing first to centromeres and then to the midzone of mitotic cells [6].
• Aurora-C transcript is expressed at a moderate level albeit about an order of magnitude lower than Aurora-B transcript in diploid human fibroblasts [6].
• Overexpression of an Aurora-C kinase-deficient mutant disrupts the Aurora-B/INCENP complex and induces polyploidy [7].
• Together, our results showed that Aurora-C is a chromosomal passenger protein, which may serve as a key regulator in cell division [7].

Anatomical context of AURKC

• Surprisingly, in few interphase cells, we found that Aurora-C localized to the centrosome, like Aurora-A [8].
• We first investigated the subcellular localization of overexpressed GFP-Aurora-C in mitosis and interphase in HeLa cells [8].
• We show that PTTG3 and AURKC are respectively the securin and the Aurora kinase preferentially expressed during oocyte meiosis [9].
• Northern blot analyses revealed that AIK3 expression was limited to testis [10].
• AIK3 gene was assigned to human chromosome 19q13.43, which is a frequently deleted or rearranged region in several tumor tissues, by fluorescence in situ hybridization, somatic cell hybrid panel, and radiation hybrid cell panel [10].

Associations of AURKC with chemical compounds

• The function of Aurora-C kinase, a member of the Aurora kinase family identified in mammals, is currently unknown [6].
• In order to study the potential role of Aurora-C, we examined the effects of a kinase-deficient (KD) mutant (AurC-KD) in HeLa Tet-Off cells under tetracycline control [7].
• Aurora-C is the third member of the aurora serine/threonine kinase family and was found only in mammals [8].
• Mammalian aurora-A belongs to a multigenic family of mitotic serine/threonine kinases comprising two other members: aurora-B and aurora-C [11].

Regulatory relationships of AURKC

• The absence of p53 aggravates polyploidy and centrosome number abnormality induced by Aurora-C overexpression [8].

Other interactions of AURKC

• Direct association with inner centromere protein (INCENP) activates the novel chromosomal passenger protein, Aurora-C [4].
• Extensive studies on the role of Aurora-A and Aurora-B have revealed distinct localizations and functions in regulating mitotic processes, whereas little is known about Aurora-C [4].
• Although the physiological function of Aurora-C in somatic cells remains to be clarified, our results, just like for the two other Aurora kinases, raised the question of a role of Aurora-C in the development and progression of cancer especially in the presence of mutated p53 [8].
• The T171A and T175A mutants, in which threonines located at residues 171 and 175 were replaced by alanines, revealed a significant increase in their kinase activities to phosphorylate ACS-1 (Aurora-C substrate 1) [12].

Analytical, diagnostic and therapeutic context of AURKC

• Immunofluorescence analysis of ectopically expressed GFP-Aurora-C has revealed that Aurora-C is a new member of the chromosomal passenger proteins localizing first to the centromeres and then to the central spindles during cytokinesis [7].
• These observations were mirrored in RT-PCR experiments for Aurora-A and B. In contrast, Aurora-C mRNA levels were not significantly different among the different cell types analyzed, suggesting that posttranscriptional mechanism(s) modulate its expression [1].
• The localization of STK13 on human chromosome 19 was confirmed by fluorescence in situ hybridization (FISH) using a genomic clone containing STK13 as a probe [13].

References