AURKA Gene

AURKA (Aurora Kinase A) Gene

Overview

AURKA (Aurora Kinase A) Gene

Overview

AURKA (Aurora Kinase A) encodes a serine/threonine kinase essential for mitotic entry, centrosome maturation, and spindle assembly["@giet2010"]. While primarily studied in cancer biology due to its frequent overexpression in tumors, AURKA also has important functions in post-mitotic [neurons](/entities/neurons), including roles in cilia function, neuronal polarity, and dendrite morphogenesis["@barr2007"]. Dysregulated AURKA may contribute to neurodegeneration through effects on cell cycle re-entry in neurons, a hallmark of several neurodegenerative diseases["@zhu2014"].

Gene Information

<div class="infobox infobox-gene">

| Property | Value |
|----------|-------|
| Gene Symbol | AURKA |
| Full Name | Aurora Kinase A |
| Chromosomal Location | 20q13.2 |
| NCBI Gene ID | [6790](https://www.ncbi.nlm.nih.gov/gene/6790) |
| OMIM | [603072](https://www.omim.org/entry/603072) |
| Ensembl ID | ENSG00000087586 |
| UniProt ID | [O14965](https://www.uniprot.org/uniprot/O14965) |
| Alias | AURA, BTAK, STK15, STK6 |

</div>

Protein Structure and Function

AURKA is a member of the Aurora family of serine/threonine kinases, which also includes AURKB (Aurora Kinase B) and AURKC (Aurora Kinase C)[@carmena2003]. The protein has a conserved kinase domain flanked by N-terminal regulatory regions and C-terminal degradation motifs.

Domain Architecture

• N-terminal domain: Regulatory region containing degradation motifs (A-box, D-box)
• Kinase domain: Catalytic domain with activation loop phosphorylation site
• C-terminal domain: D-box for APC/C-mediated degradation

Catalytic Activity

AURKA kinase activity is tightly regulated:

Expression Pattern

AURKA shows high expression in proliferating cells, but is also expressed in certain post-mitotic tissues:

Brain Expression

In the nervous system, AURKA is expressed in:

• Neural progenitor cells: High expression during development
• Ependymal cells: Moderate expression in adult brain
• Certain neuronal populations: Lower but detectable in specific brain regions

Normal Cellular Functions

Mitosis Regulation

AURKA's canonical functions in dividing cells include[@marumoto2003]:

Neuronal Functions

In neurons, AURKA has additional specialized roles[@leroux2017]:

Role in Neurodegeneration

Cell Cycle Re-entry Hypothesis

One of the leading theories in neurodegeneration is that neurons inappropriately re-enter the cell cycle, leading to apoptotic cell death[@herrup2007]. AURKA plays a central role in this process:

• Cell cycle markers: Elevated AURKA is observed in AD, PD, and Huntington's disease brains
• DNA synthesis: Some neurons show evidence of incomplete DNA replication
• Cyclin expression: Aberrant cyclin expression triggers cell cycle re-entry

Alzheimer's Disease

AURKA has been specifically implicated in Alzheimer's disease[@zhu2014a]:

• [Tau](/proteins/tau) phosphorylation: AURKA can phosphorylate tau at multiple sites
• Amyloid effects: [Aβ](/proteins/amyloid-beta) exposure can upregulate AURKA expression
• Neuronal cell cycle: AURKA activation precedes neuronal death in AD models

Parkinson's Disease

In Parkinson's disease models[@liu2015]:

• [Alpha-synuclein](/proteins/alpha-synuclein): AURKA interacts with alpha-synuclein aggregation
• Mitochondrial dysfunction: AURKA may affect mitochondrial dynamics
• Dopaminergic neurons: Specific vulnerability may involve AURKA dysregulation

Amyotrophic Lateral Sclerosis

ALS research suggests[@ranganathan2009]:

• Glial proliferation: AURKA in reactive [astrocytes](/entities/astrocytes)
• Motor neuron stress: Cell cycle activation in dying motor neurons
• Therapeutic targeting: AURKA inhibitors being explored

Therapeutic Targeting

Cancer Therapy

AURKA is a validated cancer target, with several inhibitors in clinical development[@cheung2011]:

| Drug | Company | Stage | Notes |
|------|---------|-------|-------|
| Alisertib (MLN8237) | Millennium/Takeda | Phase III | Oral selective inhibitor |
| VX-680 (Tozasertib) | Vertex | Discontinued | First-generation inhibitor |
| Danusertib | Novartis | Phase II | Pan-Aurora inhibitor |

Neurodegenerative Disease

AURKA modulation for neurodegeneration is speculative but intriguing:

• Inhibitor use: Could prevent inappropriate cell cycle re-entry
• Timing: Critical window may exist early in disease process
• Side effects: Systemic inhibition may cause mitotic toxicity

Genetic Variants

Cancer-Associated Variants

| Variant | Effect | Associated Cancer |
|---------|--------|------------------|
| F31I | Gain of function | Breast cancer |
| V57I | Moderate activity | Various |
| L210F | Amplification | Ovarian cancer |

Neurodegeneration Variants

While no direct disease-causing mutations are known, expression quantitative trait loci (eQTLs) may modify disease risk.

Research Tools

Chemical Inhibitors

• Alisertib: Highly selective AURKA inhibitor
• VX-689: Potent small molecule inhibitor
• ZM447439: Broader Aurora kinase inhibitor

Genetic Tools

• siRNA/shRNA: Knockdown constructs
• CRISPR-Cas9: Gene editing approaches
• Overexpression vectors: Wild-type and mutant constructs

Summary

AURKA is a serine/threonine kinase with essential functions in cell division and emerging roles in neuronal biology. While best known as a cancer target, AURKA dysregulation may contribute to neurodegenerative diseases through aberrant cell cycle re-entry in neurons. Further research is needed to determine whether AURKA modulation could have therapeutic benefits in neurodegeneration.

See Also

• [Cell Cycle Re-entry](/mechanisms/cell-cycle-arrest)
• [Mitosis](/mechanisms/mitosis)
• [Aurora Kinase B](/entities/aurora-kinase-b)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Tau Phosphorylation](/mechanisms/tau-phosphorylation)

External Links

• [NCBI Gene: aurka](https://www.ncbi.nlm.nih.gov/gene/)
• [PubMed: aurka](https://pubmed.ncbi.nlm.nih.gov/?term=aurka+neurodegeneration)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving AURKA Gene discovered through SciDEX knowledge graph analysis: