Aurora kinase C, also Serine/threonine-protein kinase 13 is an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...
that in humans is encoded by the ''AURKC''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
Function
This gene encodes a member of the highly conserved
Aurora
An aurora (plural: auroras or aurorae), also commonly known as the polar lights, is a natural light display in Earth's sky, predominantly seen in high-latitude regions (around the Arctic and Antarctic). Auroras display dynamic patterns of bri ...
subfamily of
serine/threonine protein kinase
A serine/threonine protein kinase () is a kinase enzyme, in particular a protein kinase, that phosphorylates the OH group of the amino-acid residues serine or threonine, which have similar side chains. At least 350 of the 500+ human prote ...
s with two other members,
Aurora A
Aurora kinase A also known as serine/threonine-protein kinase 6 is an enzyme that in humans is encoded by the ''AURKA'' gene.
Aurora A is a member of a family of mitotic serine/threonine kinases. It is implicated with important processes during ...
and
Aurora B
An aurora (plural: auroras or aurorae), also commonly known as the polar lights, is a natural light display in Earth's sky, predominantly seen in high-latitude regions (around the Arctic and Antarctic). Auroras display dynamic patterns of bri ...
. 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
In cell biology, the centrosome (Latin centrum 'center' + Greek sōma 'body') (archaically cytocentre) is an organelle that serves as the main microtubule organizing center (MTOC) of the animal cell, as well as a regulator of cell-cycle pro ...
/
spindle
Spindle may refer to:
Textiles and manufacturing
* Spindle (textiles), a straight spike to spin fibers into yarn
* Spindle (tool), a rotating axis of a machine tool
Biology
* Common spindle and other species of shrubs and trees in genus '' Euony ...
function during
mitosis
In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is maint ...
. This gene is overexpressed in several cancer cell lines, suggesting an involvement in oncogenic signal transduction.
Alternative splicing results in multiple transcript variants.
Function
Temporal expression patterns and
subcellular localization of Aurora kinases in mitotic cells from
G2 to
cytokinesis
Cytokinesis () is the part of the cell division process during which the cytoplasm of a single eukaryotic cell divides into two daughter cells. Cytoplasmic division begins during or after the late stages of nuclear division in mitosis and me ...
indicate association with mitotic and meiotic structure.
Although
yeast
Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to consti ...
contain only one Aurora kinase and
C. elegans
''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' ( ...
and
Drosophila
''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many s ...
contain only two, mammals have three Aurora kinases with 67-76% homology that are structurally similar and localize similarly.
Aurora C localizes to the centrosome and then to the midzone of mitotic cells from
anaphase
Anaphase () is the stage of mitosis after the process of metaphase, when replicated chromosomes are split and the newly-copied chromosomes (daughter chromatids) are moved to opposite poles of the cell. Chromosomes also reach their overall max ...
to cytokinesis. It is expressed about an order of magnitude less than Aurora B in diploid human
fibroblast
A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells of ...
s, with
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.
mRNA is created during the ...
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 cell
A somatic cell (from Ancient Greek σῶμα ''sôma'', meaning "body"), or vegetal cell, is any biological cell forming the body of a multicellular organism other than a gamete, germ cell, gametocyte or undifferentiated stem cell. Such cells co ...
s, Aurora C is more often expressed during meiosis (
spermatogenesis
Spermatogenesis is the process by which haploid spermatozoa develop from germ cells in the seminiferous tubules of the testis. This process starts with the mitotic division of the stem cells located close to the basement membrane of the t ...
and
oogenesis
Oogenesis, ovogenesis, or oögenesis is the differentiation of the ovum (egg cell) into a cell competent to further develop when fertilized. It is developed from the primary oocyte by maturation. Oogenesis is initiated in the embryonic stage.
O ...
).
Aurora B kinase regulates
kinetochore
A kinetochore (, ) is a disc-shaped protein structure associated with duplicated chromatids in eukaryotic cells where the spindle fibers attach during cell division to pull sister chromatids apart. The kinetochore assembles on the centromere ...
maturation, destabilization of improper kinetochore-
microtubule attachments, and
spindle assembly checkpoint
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 mitosis or meiosis that prevents the separa ...
(SAC),
central spindle The central spindle is a microtubule based structure, which forms in between segregating chromosomes during anaphase where the two sets of microtubules, emanating from opposite halves of the cell, overlap, and become arranged into antiparallel bund ...
organization, and cytokinesis.
Aneuploidy
Aneuploidy is the presence of an abnormal number of chromosomes in a cell, for example a human cell having 45 or 47 chromosomes instead of the usual 46. It does not include a difference of one or more complete sets of chromosomes. A cell with a ...
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.
Clinical significance
Expression is typically limited to meiotic cells, but overexpression occurs in some cancer cell lines.
PLZF, a transcription
repressor
In molecular genetics, a repressor is a DNA- or RNA-binding protein that inhibits the expression of one or more genes by binding to the operator or associated silencers. A DNA-binding repressor blocks the attachment of RNA polymerase to the ...
, and its
CpG island methylation are the most studied modes of regulating AURKC regulation. Although all of the Aurora kinases are overexpressed in many cancer cell lines, only Aurora A and C possess oncogenic activity, producing
multinucleated cells
Multinucleate cells (also known as multinucleated or polynuclear cells) are eukaryotic cells that have more than one nucleus per cell, i.e., multiple nuclei share one common cytoplasm. Mitosis in multinucleate cells can occur either in a coordina ...
and tumors
in vivo
Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...
when overexpressed.
When cells overexpressing Aurora C were treated with
nocodazole
Nocodazole is an antineoplastic agent which exerts its effect in cells by interfering with the polymerization of microtubules. Microtubules are one type of fibre which constitutes the cytoskeleton, and the dynamic microtubule network has severa ...
to turn on the SAC, Aurora B protein stability and activity decreased. This then prevented activation of SAC protein
BubR1 and
phosphorylation
In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, ...
of
histone H3
Histone H3 is one of the five main histones involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domain and a long N-terminal tail, H3 is involved with the structure of the nucleosomes of the 'beads on a stri ...
and
MCAK.
Inactivating mutations of Aurora C have been shown to cause
infertility in men characterized by macrocephalic and multiflagellular
spermatozoa
A spermatozoon (; also spelled spermatozoön; ; ) is a motile sperm cell (biology), cell, or moving form of the ploidy, haploid cell (biology), cell that is the male gamete. A spermatozoon Fertilization, joins an ovum to form a zygote. (A zygote ...
. 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. Although c.144delC represents 85.5% of mutant alleles, the
nonsense mutation
In genetics, a nonsense mutation is a point mutation in a sequence of DNA that results in a premature stop codon, or a ''nonsense codon'' in the transcribed mRNA, and in leading to a truncated, incomplete, and usually nonfunctional protein produc ...
p.Y248* (13% of all mutant alleles) is present in both European and African men and can lead to infertility.
Klinefelter syndrome
Klinefelter syndrome (KS), also known as 47,XXY, is an aneuploid genetic condition where a male has an additional copy of the X chromosome. The primary features are infertility and small, poorly functioning testicles. Usually, symptoms are s ...
and
Y chromosome microdeletion Y chromosome microdeletion ''(YCM)'' is a family of genetic disorders caused by missing genes in the Y chromosome. Many men with YCM exhibit no symptoms and lead normal lives. It is present in a significant number of men with reduced fertility. R ...
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.
Interactions
Both Aurora B and C interact with the
inner centromere protein (INCENP) from the
C-terminal
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
to the conserved IN box domain, but Aurora B preferentially binds INCENP. The chromosomal passenger complex (CPC), essential for
chromosome segregation
Chromosome segregation is the process in eukaryotes by which two sister chromatids formed as a consequence of DNA replication, or paired homologous chromosomes, separate from each other and migrate to opposite poles of the nucleus. This segrega ...
, contains the four subunits: the Aurora kinase, INCENP,
survivin
Survivin, also called baculoviral inhibitor of apoptosis repeat-containing 5 or BIRC5, is a protein that, in humans, is encoded by the ''BIRC5'' gene.
Survivin is a member of the inhibitor of apoptosis (IAP) family. The survivin protein functions ...
, and
borealin (also known as dasra).
Co-expression of Aurora B and C in vivo interferes with INCENP binding, localization, and stability.
References
Further reading
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External links
* {{UCSC gene info, AURKC