Cell Cycle-dependent Expression and Centrosome Localization of a Third Human Aurora/Ipl1-related Protein Kinase, AIK3

Department of Molecular Pathobiochemistry, Gifu University, Gihu, Gifu, Japan
Journal of Biological Chemistry (Impact Factor: 4.57). 04/1999; 274(11):7334-40. DOI: 10.1074/jbc.274.11.7334
Source: PubMed


We earlier isolated cDNAs encoding novel human protein kinases AIK and AIK2 sharing high amino acid sequence identities with
Drosophila Aurora and Saccharomyces cerevisiae Ipl1 kinases whose mutations cause abnormal chromosome segregation. In the present study, a third human cDNA (AIK3) highly homologous to aurora/IPL1 was isolated, and the nucleotide sequence was determined. This cDNA encodes 309 amino acids with a predicted molecular mass
of 35.9 kDa. C-terminal kinase domain of AIK3 protein shares high amino acid sequence identities with those of Aurora/Ipl1
family protein kinases including human AIK, human AIK2, Xenopus pEg2,Drosophila Aurora, and yeast Ipl1, whereas the N-terminal domain of AIK3 protein shares little homology with any other Aurora/Ipl1 family
members. AIK3 gene was assigned to human chromosome 19q13.43, which is a frequently deleted or rearranged region in several tumor tissues,
by fluorescence in situhybridization, somatic cell hybrid panel, and radiation hybrid cell panel. Northern blot analyses revealed that AIK3 expression was limited to testis. The expression levels of AIK3 in several cancer cell lines were elevated severalfold compared
with normal fibroblasts. In HeLa cells, the endogenous AIK3 protein level is low in G1/S, accumulates during G2/M, and reduces after mitosis. Immunofluorescence studies using a specific antibody have shown that AIK3 is localized to centrosome
during mitosis from anaphase to cytokinesis. These results suggest that AIK3 may play a role(s) in centrosome function at
later stages of mitosis.

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Available from: Yoichi Matsuda, Sep 28, 2015
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    • "Diagram summarizing cell phenotypes observed when AURKC expression is disrupted in mitotic and meiotic cells. also located in the telomeric region of human Chromosome 19 (Bernard et al., 1998), a genomic region susceptible to translocations and deletions (Bernard et al., 1998; Kimura et al., 1999). Although some plasticity exists between the Aurora kinase family members allowing for functional compensation; some roles are kinase specific and maintaining the correct balance is necessary for genomic stability (Figure 2). "
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    ABSTRACT: The mammalian genome encodes three Aurora kinase protein family members: A, B, and C. While Aurora kinase A (AURKA) and B (AURKB) are found in cells throughout the body, significant protein levels of Aurora kinase C (AURKC) are limited to cells that undergo meiosis (sperm and oocyte). Despite its discovery nearly 20 years ago, we know little about the function of AURKC compared to that of the other 2 Aurora kinases. This lack of understanding can be attributed to the high sequence homology between AURKB and AURKC preventing the use of standard approaches to understand non-overlapping and meiosis I (MI)-specific functions of the two kinases. Recent evidence has revealed distinct functions of AURKC in meiosis and may aid in our understanding of why chromosome segregation during MI often goes awry in oocytes. Many cancers aberrantly express AURKC, but because we do not fully understand AURKC function in its normal cellular context, it is difficult to predict the biological significance of this expression on the disease. Here, we consolidate and update what is known about AURKC signaling in meiotic cells to better understand why it has oncogenic potential.
    Frontiers in Cell and Developmental Biology 09/2015; 3:50. DOI:10.3389/fcell.2015.00050
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    • "At present, very little information is available about the role of Aurora-C in cancers. Despite Aurora-C is hardly detected in normal somatic cells, it is highly expressed in various tumor cell lines [66–69]. One study has described the transforming potential of overexpressed Aurora-C in NIH-3T3 cells and a correlation between the level of active kinase and tumor aggressiveness of the cells injected in nude mice [48]. "
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    ABSTRACT: Anaplastic thyroid cancers (ATC) are among the most aggressive human neoplasms with a dire prognosis and a median survival time of few months from the diagnosis. The complete absence of effective therapies for ATC renders the identification of novel therapeutic approaches sorely needed. Chromosomal instability, a feature of all human cancers, is thought to represent a major driving force in thyroid cancer progression and a number of mitotic kinases showing a deregulated expression in malignant thyroid tissues are now held responsible for thyroid tumor aneuploidy. These include the three members of the Aurora family (Aurora-A, Aurora-B, and Aurora-C), serine/threonine kinases that regulate multiple aspects of chromosome segregation and cytokinesis. Over the last few years, several small molecule inhibitors targeting Aurora kinases were developed, which showed promising antitumor effects against a variety of human cancers, including ATC, in preclinical studies. Several of these molecules are now being evaluated in phase I/II clinical trials against advanced solid and hematological malignancies. In the present review we will describe the structure, expression, and mitotic functions of the Aurora kinases, their implications in human cancer progression, with particular regard to ATC, and the effects of their functional inhibition on malignant cell proliferation.
    International Journal of Endocrinology 07/2014; 2014(3):816430. DOI:10.1155/2014/816430 · 1.95 Impact Factor
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    • "In higher eukaryotes, centrosome-associated Aurora kinases are now generally termed Aurora A, to distinguish them from the Ipl1-related Aurora B kinases that are a component of the chromosome passenger complex (CPC) [24]. A third mammalian Aurora paralogue, Aurora C [25], is functionally related to Aurora B [26,27] and thought to play a role in the meiotic cell cycle, but does not seem to be essential for cell divisions in somatic cells [28–30]. "
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    ABSTRACT: The correct assembly and timely disassembly of the mitotic spindle is crucial for the propagation of the genome during cell division. Aurora kinases play a central role in orchestrating bipolar spindle establishment, chromosome alignment and segregation. In most eukaryotes, ranging from amoebas to humans, Aurora activity appears to be required both at the spindle pole and the kinetochore, and these activities are often split between two different Aurora paralogues, termed Aurora A and B. Polar and equatorial functions of Aurora kinases have generally been considered separately, with Aurora A being mostly involved in centrosome dynamics, whereas Aurora B coordinates kinetochore attachment and cytokinesis. However, double inactivation of both Aurora A and B results in a dramatic synergy that abolishes chromosome segregation. This suggests that these two activities jointly coordinate mitotic progression. Accordingly, recent evidence suggests that Aurora A and B work together in both spindle assembly in metaphase and disassembly in anaphase. Here, we provide an outlook on these shared functions of the Auroras, discuss the evolution of this family of mitotic kinases and speculate why Aurora kinase activity may be required at both ends of the spindle microtubules.
    Open Biology 03/2013; 3(3):120185. DOI:10.1098/rsob.120185 · 5.78 Impact Factor
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