WWTR1 Protein is a protein encoded by the WWTR1 gene. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
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Gene Name
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[WWTR1](/genes/wwtr1)
UniProt ID
[Q9GZV5](https://www.uniprot.org/uniprot/Q9GZV5)
PDB Structures
3MTS, 4BS2, 5C45
Molecular Weight
42.8 kDa
Subcellular Localization
Nucleus, cytoplasm
Protein Family
WW domain-containing protein family
WWTR1 (WW Domain Containing Transcription Regulator 1), also known as TAZ (Transcriptional Coactivator with PDZ-binding motif), is a 400-amino acid protein containing:
- WW domain: Mediates protein-protein interactions by binding to proline-rich motifs
- PDZ-binding motif: Interacts with PDZ domain-containing proteins
- Transactivation domain: C-terminal domain for transcriptional coactivation
- TEA domain (TEAD-binding domain): Binds to TEAD transcription factors
The protein functions primarily as a transcriptional coactivator, lacking DNA-binding capability but modulating gene expression through interactions with various transcription factors 1.
In the nervous system, WWTR1/TAZ is involved in:
- Hippo signaling pathway: Key effector that regulates neuronal survival and growth
- Neural stem cell maintenance: Controls stem cell proliferation and differentiation
- Axon regeneration: Modulates the response to neuronal injury
- Synaptic plasticity: Influences dendritic spine formation and synaptic function
- Transcriptional regulation: Coactivates genes involved in neuroprotection
TAZ is expressed in neural progenitor cells and mature neurons, with roles in brain development and homeostasis 2.
- TAZ/Hippo signaling is dysregulated in AD brain tissue
- The protein interacts with tau pathology and may modulate tau toxicity
- Neuroprotective signaling through YAP/TAZ is impaired in AD
- May contribute to synaptic dysfunction through altered transcription 3
- Hippo pathway activation is observed in PD models
- TAZ may protect against dopaminergic neuron death
- Interactions with alpha-synuclein pathology are being investigated
- Modulates ER stress response in dopaminergic neurons
¶ Stroke and Ischemia
- YAP/TAZ signaling is protective in cerebral ischemia
- Activation promotes neuronal survival after stroke
- Potential therapeutic target for stroke intervention
- Dysregulated Hippo/TAZ signaling contributes to impaired brain development
- Associated with intellectual disability in some cases
- Hippo pathway modulators: Small molecules activating YAP/TAZ are under development
- Gene therapy: Viral vectors delivering TAZ for neuroprotection
- No direct TAZ-targeted drugs are currently approved for neurodegeneration
- TAZ as a transcriptional coactivator in Hippo signaling (2011)
- Role of TAZ in neural development and disease (2015)
- Hippo pathway in Alzheimer's disease (2017)
- YAP/TAZ in cerebral ischemia and neuroprotection (2018)