AURKC — Aurora Kinase C

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AURKC — Aurora Kinase C

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">AURKC</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>AURKC</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Aurora Kinase C</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>19q13.43</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>6795</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000171495</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>604615</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q96GF4</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Aurora kinase family (serine/threonine kinases)</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td>Male Infertility, Oocyte Aneuploidy, Cancer</td>
</tr>
</table>

AURKC — Aurora Kinase C

Overview

AURKC (Aurora Kinase C) is a serine/threonine kinase that plays essential roles in cell division, particularly during meiosis. As a member of the Aurora kinase family (alongside AURKA and AURKB), AURKC is critical for chromosome segregation, cytokinesis, and the proper formation of the mitotic and meiotic spindle. While primarily expressed in testis and ovaries, alterations in Aurora kinase signaling have been noted in neurodegenerative conditions, where cell cycle dysregulation is a recognized feature[@yang2005][@carmena2014].

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AURKC — Aurora Kinase C

Overview

The gene encodes a 309-amino acid protein that localizes to centrosomes and spindle poles during cell division. Unlike AURKA (primarily mitotic) and AURKB (broadly expressed in mitosis and meiosis), AURKC demonstratestestis-specific expression with essential functions in spermatogenesis and oogenesis.

Function

Protein Structure and Regulation

AURKC shares structural features with other Aurora kinases:

N-terminal domain: Regulatory domain controlling kinase activity
Catalytic domain: Conserved serine/threonine kinase domain
C-terminal domain: Stabilizes protein-protein interactions
Destruction box (D-box): Targets the protein for degradation after mitosis

The kinase activity of AURKC is regulated by:

Phosphorylation at Thr153 (activation loop)
Autophosphorylation during cell division
Interaction with the Chromosome Passenger Complex (CPC)[@tang2006]

Chromosome Passenger Complex

AURKC participates in the Chromosome Passenger Complex, which includes:

INCENP: Inner centromere protein that scaffolds the complex
Survivin (BIRC5): Centromere binding subunit
Borealin (CDCA8): Complex stability and localization

The CPC orchestrates critical mitotic and meiotic events:

Chromosome alignment and segregation
Spindle checkpoint signaling
Cytokinesis initiation

Biological Functions

Meiosis Regulation

AURKC is essential for proper progression through meiosis I and II[@kimmins2007][@kurita2008]:

Spindle Assembly: Required for proper assembly of the meiotic spindle in oocytes and spermatocytes

Chromosome Segregation: Ensures accurate chromosome distribution during meiotic divisions

Cytokinesis: Controls completion of cell division in germ cells

Spindle Checkpoint: Participates in monitoring chromosome-spindle attachments

Spermatogenesis

In male germ cells, AURKC performs critical functions[@yang2005][@yan2008]:

Expressed primarily in spermatocytes undergoing meiosis I
Essential for the first meiotic division
Required for proper spermatid formation
Mutations cause male infertility (asthenozoospermia, teratozoospermia)

Oogenesis

In female germ cells, AURKC contributes to[@hassold2008][@khanna2011]:

Meiotic spindle assembly in oocytes
Proper chromosome alignment
Prevention of aneuploidy
Oocyte maturation

Cell Cycle Regulation

Aurora kinases regulate cell cycle progression through multiple mechanisms[@dutta2008]:

G2/M Transition: AURKC activity peaks during G2/M transition
Mitotic Entry: Phosphorylation of substrates triggers mitotic entry
Metaphase Checkpoint: CPC components monitor kinetochore-microtubule attachments
Anaphase Onset: CPC relocation triggers anaphase onset
Cytokinesis: Aurora B (and likely AURKC) coordinates contractile ring formation

Disease Associations

Male Infertility

AURKC is a major cause of male infertility due to meiotic defects[@chiang2010]:

Clinical Presentations:

Oligospermia (reduced sperm count)
Asthenozoospermia (reduced motility)
Teratozoospermia (abnormal morphology)
Complete male infertility in homozygous mutation carriers

Molecular Mechanisms:

Impaired meiotic spindle assembly
Chromosome segregation errors
Abnormal cytokinesis in spermatocytes
Apoptotic elimination of abnormal germ cells

Genetic Basis:

Recessive AURKC mutations cause male infertility
Compound heterozygous variants identified in infertile males
Founder mutations in certain populations

Oocyte Aneuploidy

AURKC dysfunction contributes to aneuploidy in human oocytes[@hassold2008]:

Elevated AURKC expression associated with increased aneuploidy rates
Mutations in AURKC increase risk of aneuploid conceptions
Maternal age-related decline in oocyte quality linked to Aurora kinase changes
Potential target for improving IVF outcomes

Cancer

Although AURKC is typically not expressed in somatic tissues, overexpression is observed in cancers[@villa2008][@hernando2000]:

Testicular germ cell tumors
Cancers with mitotic checkpoint defects
Potential therapeutic target for Aurora kinase inhibitors
Biomarker for aggressive disease in some contexts

Role in Neurodegeneration

Cell Cycle Dysregulation

Cell cycle dysregulation is a recognized feature of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic Lateral Sclerosis (ALS)[@mueller2019]. While AURKC is not normally expressed in post-mitotic neurons, the broader Aurora kinase pathway intersects with neurodegeneration:

Neuronal Re-entry

Post-mitotic neurons can inappropriately re-enter the cell cycle:

DNA damage triggers cell cycle re-entry
Aberrant cell cycle activity leads to apoptosis
Contributes to neuronal loss in AD and PD

DNA Damage Response

Neurons are particularly vulnerable to DNA damage:

Accumulation of DNA lesions with aging
Limited DNA repair capacity in neurons
Cell cycle activation as damage response

Aurora Kinase Signaling in Neurons

While AURKC is testis-specific, related kinases contribute to neuronal function[@bertolin2016]:

AURKA and AURKB expressed in developing neurons
Required for proper neuronal progenitor proliferation
Potential therapeutic targets for neuroprotection

Therapeutic Implications

Understanding cell cycle dysregulation in neurodegeneration provides therapeutic opportunities:

| Approach | Target | Rationale |
|----------|--------|-----------|
| Cell cycle inhibitors | CDK4/6, Aurora kinases | Prevent neuronal re-entry |
| DNA damage repair | p53, ATM pathway | Protect neurons from apoptosis |
| Neuroprotective agents | Multiple pathways | Maintain neuronal survival |

Therapeutic Approaches

Male Infertility

Current Approaches:

ICSI (Intracytoplasmic Sperm Injection) for infertility treatment
Testicular sperm extraction in some cases

Emerging Therapies:

Gene therapy approaches for AURKC correction
Small molecule activators to improve sperm motility
Screening for genetic causes before IVF

Cancer Therapy

Aurora kinase inhibitors have been developed for cancer treatment[@dutta2008]:

| Drug | Target | Status |
|------|--------|--------|
| Alisertib (MLN8237) | AURKA/AURKC | Phase 1-2 trials |
| AZD1152 | Aurora B | Phase 1-2 trials |
| Danusertib | Pan-Aurora | Phase 1-2 trials |

Challenges:

Toxicity due to effects on normal proliferating cells
Limited therapeutic window
Resistance development

External Links

[NCBI Gene: AURKC](https://www.ncbi.nlm.nih.gov/gene/6795)
[UniProt: Q96GF4](https://www.uniprot.org/uniprot/Q96GF4)
[OMIM: 604615](https://omim.org/entry/604615)
[GeneCards: AURKC](https://www.genecards.org/cgi-bin/carddisp.pl?gene=AURKC)
[ClinVar: AURKC variants](https://www.ncbi.nlm.nih.gov/clinvar/?term=AURKC)

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AURKC — Aurora Kinase C

AURKC — Aurora Kinase C

AURKC — Aurora Kinase C

Overview

AURKC — Aurora Kinase C

AURKC — Aurora Kinase C

Overview

Function

Protein Structure and Regulation

Chromosome Passenger Complex

Biological Functions

Meiosis Regulation

Spermatogenesis

Oogenesis

Cell Cycle Regulation

Disease Associations

Male Infertility

Oocyte Aneuploidy

Cancer

Role in Neurodegeneration

Cell Cycle Dysregulation

Neuronal Re-entry

DNA Damage Response

Aurora Kinase Signaling in Neurons

Therapeutic Implications

Therapeutic Approaches

Male Infertility

Cancer Therapy

See Also

External Links