| AURKC | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | AURKC , AIE2, AIK3, ARK3, AurC, SPGF5, STK13, aurora-C, HEL-S-90, aurora kinase C | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 603495 MGI: 1321119 HomoloGene: 68302 GeneCards: AURKC | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aurora kinase C, also Serine/threonine-protein kinase 13 is an enzyme that in humans is encoded by the AURKC gene. [5] [6]
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 G2 to cytokinesis 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 phosphorylation of histone 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]
The spindle checkpoint, also known as the metaphase-to-anaphase transition, the spindle assembly checkpoint (SAC), the metaphase checkpoint, or the mitotic checkpoint, is a cell cycle checkpoint during metaphase of mitosis or meiosis that prevents the separation of the duplicated chromosomes (anaphase) until each chromosome is properly attached to the spindle. To achieve proper segregation, the two kinetochores on the sister chromatids must be attached to opposite spindle poles. Only this pattern of attachment will ensure that each daughter cell receives one copy of the chromosome. The defining biochemical feature of this checkpoint is the stimulation of the anaphase-promoting complex by M-phase cyclin-CDK complexes, which in turn causes the proteolytic destruction of cyclins and proteins that hold the sister chromatids together.
Aurora kinases are serine/threonine kinases that are essential for cell proliferation. They are phosphotransferase enzymes that help the dividing cell dispense its genetic materials to its daughter cells. More specifically, Aurora kinases play a crucial role in cellular division by controlling chromatid segregation. Defects in this segregation can cause genetic instability, a condition which is highly associated with tumorigenesis. The first aurora kinases were identified in Drosophila melanogaster, where mutations led to failure of centrosome separation with the monopolar spindles reminiscent of the North Pole, suggesting the name aurora.
Aurora kinase A also known as serine/threonine-protein kinase 6 is an enzyme that in humans is encoded by the AURKA gene.
Aurora kinase B is a protein that functions in the attachment of the mitotic spindle to the centromere.
Aurora kinase inhibitors are a putative drug class for treating cancer. The Aurora kinase enzymes could be potential targets for novel small-molecule enzyme inhibitors.
David Moore Glover is a British geneticist and Research Professor of Biology and Biological Engineering at the California Institute of Technology. He served as Balfour Professor of Genetics at the University of Cambridge, a Wellcome Trust investigator in the Department of Genetics at the University of Cambridge, and Fellow of Fitzwilliam College, Cambridge. He serves as the first editor-in-chief of the open-access journal Open Biology published by the Royal Society.
Polo-like kinases (Plks) are regulatory serine/threonine kinases of the cell cycle involved in mitotic entry, mitotic exit, spindle formation, cytokinesis, and meiosis. Only one Plk is found in the genomes of the fly Drosophila melanogaster (Polo), budding yeast (Cdc5) and fission yeast (Plo1). Vertebrates and other animals, however, have many Plk family members including Plk1, Plk2/Snk, Plk3/Prk/FnK, Plk4/Sak and Plk5. Of the vertebrate Plk family members, the mammalian Plk1 has been most extensively studied. During mitosis and cytokinesis, Plks associate with several structures including the centrosome, kinetochores, and the central spindle.
Serine/threonine-protein kinase PLK1, also known as polo-like kinase 1 (PLK-1) or serine/threonine-protein kinase 13 (STPK13), is an enzyme that in humans is encoded by the PLK1 gene.
Mitotic checkpoint serine/threonine-protein kinase BUB1 beta is an enzyme that in humans is encoded by the BUB1B gene. Also known as BubR1, this protein is recognized for its mitotic roles in the spindle assembly checkpoint (SAC) and kinetochore-microtubule interactions that facilitate chromosome migration and alignment. BubR1 promotes mitotic fidelity and protects against aneuploidy by ensuring proper chromosome segregation between daughter cells. BubR1 is proposed to prevent tumorigenesis.
Neural precursor cell expressed developmentally down-regulated protein 9 (NEDD-9) is a protein that in humans is encoded by the NEDD9 gene. NEDD-9 is also known as enhancer of filamentation 1 (EF1), CRK-associated substrate-related protein (CAS-L), and Cas scaffolding protein family member 2 (CASS2). An important paralog of this gene is BCAR1.
Kinesin-like protein KIF23 is a protein that in humans is encoded by the KIF23 gene.
Inner centromere protein is a protein that in humans is encoded by the INCENP gene. It is a regulatory protein in the chromosome passenger complex (CPC). It is involved in regulation of the catalytic proteins Aurora B and Aurora C. It acts in association with two other proteins - Survivin and Borealin. These proteins form a tight three-helical bundle. The N-terminal domain of INCENP is the domain involved in formation of this three-helical bundle while its C-terminal domain is responsible for the interaction with Aurora B.
Targeting protein for Xklp2 is a protein that in humans is encoded by the TPX2 gene. It is one of the many spindle assembly factors that play a key role in inducing microtubule assembly and growth during M phase.
Borealin is a protein that in humans is encoded by the CDCA8 gene.
Serine/threonine-protein kinase Nek6 is an enzyme that in humans is encoded by the NEK6 gene.
Pericentrin (kendrin), also known as PCNT and pericentrin-B (PCNTB), is a protein which in humans is encoded by the PCNT gene on chromosome 21. This protein localizes to the centrosome and recruits proteins to the pericentriolar matrix (PCM) to ensure proper centrosome and mitotic spindle formation, and thus, uninterrupted cell cycle progression. This gene is implicated in many diseases and disorders, including congenital disorders such as microcephalic osteodysplastic primordial dwarfism type II (MOPDII) and Seckel syndrome.
Dual specificity protein phosphatase CDC14A is an enzyme that in humans is encoded by the CDC14A gene.
JADE1 is a protein that in humans is encoded by the JADE1 gene.
G2/mitotic-specific cyclin-F is a protein that in humans is encoded by the CCNF gene.
Cdc14 and Cdc14 are a gene and its protein product respectively. Cdc14 is found in most of the eukaryotes. Cdc14 was defined by Hartwell in his famous screen for loci that control the cell cycle of Saccharomyces cerevisiae. Cdc14 was later shown to encode a protein phosphatase. Cdc14 is dual-specificity, which means it has serine/threonine and tyrosine-directed activity. A preference for serines next to proline is reported. Many early studies, especially in the budding yeast Saccharomyces cerevisiae, demonstrated that the protein plays a key role in regulating late mitotic processes. However, more recent work in a range of systems suggests that its cellular function is more complex.
