AURKA Protein

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AURKA Protein

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">AURKA Protein</th>
</tr>
<tr>
<td class="label">Partner</td>
<td>Interaction</td>
</tr>
<tr>
<td class="label">TPX2</td>
<td>Direct binding</td>
</tr>
<tr>
<td class="label">Ajap1</td>
<td>Interaction</td>
</tr>
<tr>
<td class="label">p53</td>
<td>Phosphorylation</td>
</tr>
<tr>
<td class="label">LKB1</td>
<td>Phosphorylation</td>
</tr>
<tr>
<td class="label">HDAC6</td>
<td>Deacetylation</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/carcinoma" style="color:#ef9a9a">Carcinoma</a>, <a href="/wiki/cardiovascular" style="color:#ef9a9a">Cardiovascular</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">97 edges</a></td>
</tr>
</table>

AURKA (Aurora Kinase A), also known as Aurora A, is a serine/threonine protein kinase encoded by the AURKA gene located on chromosome 20. AURKA is a master regulator of mitosis, controlling centrosome maturation, spindle assembly, and proper chromosome segregation. While primarily studied in the context of cancer biology, AURKA has emerging roles in neuronal development and neurodegenerative diseases.

Structure

...

AURKA Protein

Introduction

Structure

AURKA is a 403-amino acid protein with a molecular weight of approximately 46 kDa. The protein consists of several functional domains:

Catalytic Domain

N-terminal domain (residues 1-127): Regulatory region containing the Aurora-box motif
Kinase domain (residues 128-391): Catalytic serine/threonine kinase domain
C-terminal domain (residues 392-403): Destruction box (D-box) for degradation

Key Structural Features

Activation loop: Contains threonine-288 (T288) that requires phosphorylation for full activity

Aurora-box: N-terminal motif important for localization and substrate recognition

D-box: Destruction box mediating ubiquitin-dependent degradation

A-box: Negative regulatory motif

The crystal structure of AURKA has been solved (PDB: 1OL5, 2DWB), revealing the typical bilobal kinase fold with the catalytic site located in a deep cleft between the N-terminal and C-terminal lobes. [@aurkaa]

Normal Function

Mitosis Regulation

AURKA is essential for mitotic progression through multiple mechanisms:

Centrosome Maturation

AURKA accumulates at centrosomes during G2/M transition
Recruits and activates pericentriolar material (PCM) proteins
Promotes centrosome separation and maturation
Essential for proper spindle pole formation

Spindle Assembly

Phosphorylates microtubule-associated proteins (MAPs)
Stabilizes spindle microtubules
Promotes bipolar spindle formation
Regulates spindle assembly checkpoint

Chromosome Segregation

Phosphorylates histone H3 at serine-10 (H3S10ph)
Modifies centromere and kinetochore function
Ensures proper chromosome alignment
Prevents aneuploidy

Cytokinesis

Localizes to midbody during cytokinesis
Regulates abscission
Controls completion of cell division

Non-Mitotic Functions

Beyond mitosis, AURKA has additional cellular roles:

DNA damage response: Involved in ATM/ATR pathway activation
Cellular polarity: Regulates apical-basal polarity in epithelial cells
Ciliogenesis: Important for primary cilia formation
Pluripotency maintenance: Regulates stem cell function

Role in Neurodegeneration

Alzheimer's Disease

AURKA has complex and context-dependent roles in Alzheimer's disease:

Cell Cycle Re-entry

[Neurons](/entities/neurons) in AD brain show mitotic markers, including AURKA activation
Aberrant cell cycle re-entry is a hallmark of vulnerable neurons
AURKA may promote inappropriate mitotic attempts in post-mitotic neurons
Leads to neuronal dysfunction and death [@aurka2020]

[Amyloid-beta](/proteins/amyloid-beta) Effects

Aβ oligomers can activate AURKA in neurons
Creates toxic signaling cascade
Contributes to synaptic dysfunction

[Tau](/proteins/tau) Pathology

AURKA can phosphorylate tau at multiple sites
May contribute to tau hyperphosphorylation
Links cell cycle abnormalities to neurofibrillary pathology

Therapeutic Implications

AURKA inhibitors show protective effects in AD models
Alisertib and other AURKA inhibitors in preclinical testing
Must balance mitotic inhibition with potential side effects

Parkinson's Disease

Dopaminergic Neuron Vulnerability

AURKA expression altered in PD brain
May affect protein clearance mechanisms
Links cell cycle dysregulation to dopaminergic neuron loss

[Alpha-synuclein](/proteins/alpha-synuclein) Pathology

AURKA can phosphorylate alpha-synuclein at serine-129
This phosphorylation promotes aggregation
AURKA activity may accelerate Lewy body formation [@aurkab]

Amyotrophic Lateral Sclerosis (ALS)

Motor Neuron Development

AURKA essential for proper motor neuron development
Mutations cause neurodevelopmental defects
May affect motor neuron connectivity

Protein Homeostasis

AURKA regulates [autophagy](/entities/autophagy) pathways
Dysfunction may contribute to protein aggregate accumulation
Links cell cycle to protein quality control

Brain Development

Neural Progenitor Cells

AURKA critical for neural progenitor cell proliferation
Regulates symmetric versus asymmetric division
Microcephaly seen in AURKA gain-of-function mutants

Axon Guidance

AURKA localizes to growth cones
Regulates cytoskeletal dynamics
Important for neuronal connectivity

Therapeutic Targeting

Cancer Therapy

AURKA is a validated cancer target:

Clinical Inhibitors

Alisertib (MLN8237): Oral selective AURKA inhibitor in clinical trials
VX-680 (Tozasertib): Pan-aurora kinase inhibitor
AMG 900: Potent pan-aurora inhibitor

Mechanism

Induces mitotic arrest and [apoptosis](/entities/apoptosis) in dividing cells
Effective in tumors with AURKA amplification
Being tested in solid tumors and hematological malignancies

Neurodegeneration Therapy

Potential applications in AD/PD:

AURKA Inhibitors

Lower doses than cancer therapy
Must cross [blood-brain barrier](/entities/blood-brain-barrier)
Protective in cellular and mouse models

Combination Approaches

AURKA + tau kinase inhibitors
AURKA + autophagy modulators
Disease-modifying potential

Research Methods

Studying AURKA in neurodegeneration:

Kinase activity assays: Measure AURKA activity in brain tissue
Phospho-antibodies: Detect phosphorylated substrates
Inhibitor studies: Use Alisertib, VX-680 in models
Genetic models: Transgenic mice, knockdown/knockout systems

Interactions and Pathways

AURKA interacts with multiple proteins:

External Links

[UniProt O14965](https://www.uniprot.org/uniprot/O14965)
[PDB: 1OL5](https://www.rcsb.org/structure/1OL5)
[GeneCards AURKA](https://www.genecards.org/cgi-bin/carddisp.pl?gene=AURKA)
[NCBI Gene AURKA](https://www.ncbi.nlm.nih.gov/gene/6790)

References

Unknown, AURKA gene description - NCBI Gene (n.d.)

[Barr et al., Aurora kinases in mitosis - Nature Reviews Molecular Cell Biology (n.d.)](https://doi.org/10.1038/nrm2330)

[Unknown, AURKA crystal structure - Structure (n.d.)](https://doi.org/10.1016/S0969-2126(00)

[Unknown, AURKA in Alzheimer's disease - Neurobiology of Aging (2020)](https://doi.org/10.1016/j.neurobiolaging.2020.03.012)

[Unknown, AURKA phosphorylates alpha-synuclein - Nature Cell Biology (n.d.)](https://doi.org/10.1038/ncb1800)

[Unknown, Aurora kinase inhibitors in clinical development - Clinical Cancer Research (n.d.)](https://doi.org/10.1158/1078-0432.CCR-13-2406)

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AURKA Protein

AURKA Protein

Introduction

Structure

AURKA Protein

Introduction

Structure

Catalytic Domain

Key Structural Features

Normal Function

Mitosis Regulation

Non-Mitotic Functions

Role in Neurodegeneration

Alzheimer's Disease

Parkinson's Disease

Amyotrophic Lateral Sclerosis (ALS)

Brain Development

Therapeutic Targeting

Cancer Therapy

Neurodegeneration Therapy

Research Methods

Interactions and Pathways

See Also

External Links

References