AURKC — Aurora Kinase C

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].

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].

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

• 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

• 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]:

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

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

• 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

• 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

See Also

• [Cell Cycle](/mechanisms/cell-cycle) - Cell division mechanisms
• [Meiosis](/mechanisms/meiosis) - Germ cell division
• [Apoptosis](/mechanisms/apoptosis) - Cell death pathways
• [DNA Damage](/mechanisms/dna-damage) - Genomic stress responses
• [Alzheimer's Disease](/diseases/alzheimers-disease) - AD overview
• [Parkinson's Disease](/diseases/parkinsons-disease) - PD overview

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)