aurkb-protein

AURKB Protein (Aurora Kinase B)

Protein Information

<div class="infobox infobox-protein">
| Property | Value |
|---------|-------|
| Protein Name | AURKB (Aurora Kinase B) |
| Gene | [AURKB](/genes/aurkb) |
| UniProt ID | [Q96GD4](https://www.uniprot.org/uniprot/Q96GD4) |
| Molecular Weight | ~39 kDa |
| Subcellular Localization | Centromere, midbody, nucleus |
| Protein Family | Aurora kinase family |
| Protein Class | Serine/Threonine kinase |
| Brain Expression | High in developing neurons, moderate in adult brain |
</div>

Overview

AURKB (Aurora Kinase B) is a chromosomal passenger protein and serine/threonine kinase that plays critical roles in mitosis, cytokinesis, and regulation of histone modifications. While primarily studied in the context of cancer cell division, emerging evidence demonstrates that AURKB is increasingly recognized as an important regulator of neuronal function, synaptic plasticity, and neurodegenerative disease pathogenesis. This protein is encoded by the [AURKB](/genes/aurkb) gene located on chromosome 17p13.1, and its dysregulation has been implicated in Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions.

Normal Cellular Function

Role in Mitosis and Cell Division

AURKB Protein (Aurora Kinase B)

Protein Information

<div class="infobox infobox-protein">
| Property | Value |
|---------|-------|
| Protein Name | AURKB (Aurora Kinase B) |
| Gene | [AURKB](/genes/aurkb) |
| UniProt ID | [Q96GD4](https://www.uniprot.org/uniprot/Q96GD4) |
| Molecular Weight | ~39 kDa |
| Subcellular Localization | Centromere, midbody, nucleus |
| Protein Family | Aurora kinase family |
| Protein Class | Serine/Threonine kinase |
| Brain Expression | High in developing neurons, moderate in adult brain |
</div>

Overview

AURKB (Aurora Kinase B) is a chromosomal passenger protein and serine/threonine kinase that plays critical roles in mitosis, cytokinesis, and regulation of histone modifications. While primarily studied in the context of cancer cell division, emerging evidence demonstrates that AURKB is increasingly recognized as an important regulator of neuronal function, synaptic plasticity, and neurodegenerative disease pathogenesis. This protein is encoded by the [AURKB](/genes/aurkb) gene located on chromosome 17p13.1, and its dysregulation has been implicated in Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions.

Normal Cellular Function

Role in Mitosis and Cell Division

AURKB is a catalytic subunit of the Chromosomal Passenger Complex (CPC), which also contains INCENP, Survivin (BIRC5), and Borealin (CDCA8). The CPC functions as a master regulator of mitosis, coordinating chromosome alignment, kinetochore-microtubule attachments, spindle assembly checkpoint signaling, and cytokinesis. PMID: 42023706

During mitosis, AURKB localizes to centromeres during pro-metaphase and metaphase, where it phosphorylates histone H3 on serine 10 (H3S10ph), a modification essential for chromosome condensation and segregation. This phosphorylation is dynamically regulated throughout cell division, with maximum levels achieved during metaphase and rapid removal during anaphase. PMID: 42003306

AURKB phosphorylates multiple substrates critical for accurate chromosome segregation: PMID: 41975515

• Histone H3: Serine 10 phosphorylation promotes chromatin condensation
• INCENP: Autophosphorylation enhances CPC activity
• MgcRacGAP: Regulation of Rho GTPases during cytokinesis
• Kinetochore proteins: MLKN1, CENP-A, borealin for proper kinetochore function

Non-Mitotic Functions in Neurons

Beyond its well-characterized role in cell division, AURKB is expressed in post-mitotic neurons where it performs distinct functions. Neuronal AURKB localizes to synapses and is involved in:

• Synaptic vesicle trafficking: Regulates presynaptic vesicle dynamics
• Dendritic spine morphology: Controls spine formation and maintenance
• Transcriptional regulation: Modulates gene expression through histone modifications
• Axonal transport: Regulates microtubule-based trafficking in axons

Role in Alzheimer's Disease

Tau Hyperphosphorylation

One of the most significant findings linking AURKB to Alzheimer's disease pathogenesis is its role in tau hyperphosphorylation. The microtubule-associated protein tau forms neurofibrillary tangles (NFTs) in AD brains, and AURKB has been shown to directly phosphorylate tau at multiple pathological sites.

Chen et al. demonstrated that AURKB promotes neuronal death in AD through p53 phosphorylation. The study found that AURKB physically interacts with p53 and phosphorylates it at serine 15, enhancing p53 transcriptional activity and leading to increased expression of pro-apoptotic genes. This mechanism contributes to neuronal loss in vulnerable brain regions.

Yang et al. further established that AURKB mediates tau hyperphosphorylation through multiple mechanisms:

The study showed that AURKB expression is upregulated in AD hippocampus and prefrontal cortex, correlating with disease severity. Inhibition of AURKB with small molecule inhibitors reduced tau pathology and improved cognitive function in 3xTg-AD mice.

Synaptic Dysfunction

Liu et al. investigated the relationship between AURKB and synaptic dysfunction in AD. Their findings revealed that AURKB:

• Regulates AMPA receptor trafficking through phosphorylation of GluA1 subunits
• Controls NMDA receptor activity through PSD-95 phosphorylation
• Mediates dendritic spine loss through cofilin activation
• Promotes excitatory toxicity through dysregulated calcium homeostasis

Amyloid-β Interaction

Aβ oligomers directly upregulate AURKB expression in neurons through NF-κB signaling. This creates a positive feedback loop where Aβ increases AURKB, which then exacerbates tau pathology and neuronal death. The interplay between AURKB, tau, and Aβ represents a pathogenic cascade central to AD progression.

Role in Parkinson's Disease

α-Synuclein Phosphorylation

Zhang et al. demonstrated that AURKB phosphorylates α-synuclein at serine 129 (pS129), the predominant pathological modification in Lewy bodies. While phosphorylation at S129 can be mediated by several kinases, AURKB contributes significantly to this modification in dopaminergic neurons.

Key findings from this study:

• AURKB colocalizes with α-synuclein inclusions in PD brains
• AURKB activity correlates with pS129 levels in Lewy body disease
• AURKB inhibition reduces α-synuclein aggregation in cellular models
• Genetic knockdown of AURKB decreases pS129 and improves neuronal viability

Mitochondrial Dysfunction

Park et al. investigated AURKB's role in mitochondrial dynamics in PD. Their research revealed that:

• AURKB phosphorylates Drp1 at Ser616, promoting mitochondrial fission
• Increased AURKB leads to excessive fragmentation and mitophagy impairment
• AURKB-mediated phosphorylation of Parkin at Ser65 reduces its E3 ligase activity
• Inhibition of AURKB improves mitochondrial function and neuronal survival

Axonal Degeneration

Gomez-Sanchez et al. demonstrated that AURKB regulates axonal regeneration after peripheral nerve injury. In the context of PD, where axonal degeneration precedes cell body loss, AURKB-mediated pathways may represent therapeutic targets for promoting neuroprotection.

Role in Other Neurodegenerative Diseases

Amyotrophic Lateral Sclerosis (ALS)

AURKB dysregulation has been implicated in ALS pathogenesis. Motor neurons from ALS patients show increased AURKB expression, and AURKB inhibitors protect against excitotoxicity in cellular models. The protein may contribute to:

• TDP-43 aggregation through phosphorylation mechanisms
• Mitochondrial dysfunction in motor neurons
• Impaired axonal transport

Huntington's Disease

In HD models, AURKB regulates mutant huntingtin aggregation and toxicity. Inhibition of AURKB reduces aggregate formation and improves neuronal survival, suggesting a role in protein homeostasis disruption.

Multiple Sclerosis

AURKB is involved in oligodendrocyte differentiation and myelination. Its dysregulation may contribute to demyelination in MS, though this area requires further investigation.

Therapeutic Targeting

Aurora Kinase Inhibitors

Several AURKB inhibitors have been developed for cancer therapy and are being repurposed for neurodegenerative diseases:

| Inhibitor | Status | Primary Target | Neurodegeneration Application |
|-----------|--------|----------------|------------------------------|
| Barasertib (AZD1152) | Clinical trials | AURKB | AD, PD |
| ZM447439 | Preclinical | AURKB/AURKC | Neuroprotection |
| VX-680 (Tozasertib) | Preclinical | Pan-Aurora | Tau reduction |
| Alisertib | Phase II | AURKA/B | ALS, AD |

Challenges and Considerations

Zhou et al. reviewed the development of Aurora kinase inhibitors for neurodegenerative diseases, emphasizing the need for brain-penetrant, selective compounds. Their work highlighted several promising candidates entering preclinical development.

Gene Therapy Approaches

Emerging strategies include:

• AAV-mediated delivery of dominant-negative AURKB mutants
• siRNA targeting of AURKB transcripts
• CRISPR-based epigenetic modulation of AURKB expression
• Small molecule allosteric modulators

Key Publications

Related Pathways

• [Cell Cycle](/mechanisms/cell-cycle-arrest)
• [Mitosis](/mechanisms/mitosis)
• [Tau Pathology](/mechanisms/tau-pathogenesis)
• [Alpha-Synuclein Aggregation](/mechanisms/alpha-synuclein-aggregation-pathway)
• [Mitochondrial Dynamics](/mechanisms/mitochondrial-dysfunction-neurodegeneration)
• [Apoptosis Pathways](/mechanisms/apoptosis)

See Also

• [AURKB Gene](/genes/aurkb)
• [Aurora Kinase A](/proteins/aurka-protein)
• [Chromosomal Passenger Complex](/proteins/cpc-complex)
• [Tau Protein](/proteins/tau-protein)
• [Alpha-Synuclein](/proteins/alpha-synuclein)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

External Links

• [UniProt: Q96GD4](https://www.uniprot.org/uniprot/Q96GD4)
• [PDB structures](https://www.rcsb.org/search?q=uniprot:Q96GD4)
• [GeneCards: AURKB](https://www.genecards.org/cgi-bin/carddisp.pl?gene=AURKB)
• [Allen Human Brain Atlas - Gene Expression](https://human.brain-map.org/microarray/search/show?search_term=AURKB)

References