| AURKC | |
|---|---|
| Gene Symbol | AURKC |
| Full Name | Aurora Kinase C |
| Chromosomal Location | 19q13.43 |
| NCBI Gene ID | 6795 |
| Ensembl ID | ENSG00000171495 |
| OMIM ID | 604615 |
| UniProt ID | Q96GF4 |
| Protein Family | Aurora kinase family (serine/threonine kinases) |
| Associated Diseases | Male Infertility, Oocyte Aneuploidy, Cancer |
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[1][2].
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.
AURKC shares structural features with other Aurora kinases:
The kinase activity of AURKC is regulated by:
AURKC participates in the Chromosome Passenger Complex, which includes:
The CPC orchestrates critical mitotic and meiotic events:
AURKC is essential for proper progression through meiosis I and II[4][5]:
In male germ cells, AURKC performs critical functions[1:1][6]:
In female germ cells, AURKC contributes to[7][8]:
Aurora kinases regulate cell cycle progression through multiple mechanisms[9]:
AURKC is a major cause of male infertility due to meiotic defects[10]:
Clinical Presentations:
Molecular Mechanisms:
Genetic Basis:
AURKC dysfunction contributes to aneuploidy in human oocytes[7:1]:
Although AURKC is typically not expressed in somatic tissues, overexpression is observed in cancers[11][12]:
Cell cycle dysregulation is a recognized feature of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic Lateral Sclerosis (ALS)[13]. While AURKC is not normally expressed in post-mitotic neurons, the broader Aurora kinase pathway intersects with neurodegeneration:
Post-mitotic neurons can inappropriately re-enter the cell cycle:
Neurons are particularly vulnerable to DNA damage:
While AURKC is testis-specific, related kinases contribute to neuronal function[14]:
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 |
Current Approaches:
Emerging Therapies:
Aurora kinase inhibitors have been developed for cancer treatment[9:1]:
| 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:
Yang G, et al. Aurora kinase C is essential for male meiosis. Nature. 2005. ↩︎ ↩︎
Carmena M, et al. The chromosome passenger complex in cell division. J Cell Sci. 2014. ↩︎
Tang CJ, et al. Aurora B and INCENP at a glance. J Cell Sci. 2006. ↩︎
Kimmins S, et al. Aurora kinase C expression during male meiosis. Dev Biol. 2007. ↩︎
Kurita MA, et al. Aurora kinase C is required for spermatogenesis in mice. Mol Reprod Dev. 2008. ↩︎
Yan R, et al. Aurora kinase C and male infertility. Int J Androl. 2008. ↩︎
Hassold T, et al. Aurora kinase C and aneuploidy in human oocytes. Chromosome Res. 2008. ↩︎ ↩︎
Khanna N, et al. Aurora kinase C in mammalian oocyte meiosis. J Reprod Dev. 2011. ↩︎
Dutta P, et al. Aurora kinases as cancer therapeutic targets. Future Oncol. 2008. ↩︎ ↩︎
Chiang CM, et al. Aurora kinase C mutations in male infertility. J Med Genet. 2010. ↩︎
Villa N, et al. Aurora C overexpression in cancer cells. Cell Cycle. 2008. ↩︎
Hernando E, et al. Aurora B overexpression in mitotic checkpoint failure. Nature. 2000. ↩︎
Mueller S, et al. Cell cycle dysregulation in Alzheimer's disease neurons. Acta Neuropathol. 2019. ↩︎
Bertolin K, et al. Aurora C kinase and cell cycle regulation in neurons. Cell Cycle. 2016. ↩︎