AURKA Protein
Introduction <table class="infobox infobox-protein">
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 <table class="infobox infobox-protein">
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 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 motifKinase domain (residues 128-391): Catalytic serine/threonine kinase domainC-terminal domain (residues 392-403): Destruction box (D-box) for degradationKey Structural Features
Activation loop : Contains threonine-288 (T288) that requires phosphorylation for full activityAurora-box : N-terminal motif important for localization and substrate recognitionD-box : Destruction box mediating ubiquitin-dependent degradationA-box : Negative regulatory motifThe 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 activationCellular polarity : Regulates apical-basal polarity in epithelial cellsCiliogenesis : Important for primary cilia formationPluripotency maintenance : Regulates stem cell functionRole 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 trialsVX-680 (Tozasertib) : Pan-aurora kinase inhibitorAMG 900 : Potent pan-aurora inhibitorMechanism
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 tissuePhospho-antibodies : Detect phosphorylated substratesInhibitor studies : Use Alisertib, VX-680 in modelsGenetic models : Transgenic mice, knockdown/knockout systemsInteractions and Pathways AURKA interacts with multiple proteins:
See Also
[AURKA Gene](/genes/aurka)
[Cell Cycle](/mechanisms/cell-cycle-arrest)
[Mitosis](/mechanisms/mitosis)
[Alzheimer's Disease](/diseases/alzheimers-disease)
[Parkinson's Disease](/diseases/parkinsons-disease)
[Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis)
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) Show full description