GADD45A Protein
Introduction
Gadd45A Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
<div class="infobox infox-protein">
<div class="infobox-header">GADD45A Protein</div>
<div class="infobox-row"><span>Protein Name</span><span>Growth Arrest and DNA Damage-Inducible Alpha</span></div>
<div class="infobox-row"><span>Gene</span><span>GADD45A</span></div>
<div class="infobox-row"><span>UniProt ID</span><span>P24522</span></div>
<div class="infobox-row"><span>PDB ID</span><span>1CX4, 2LQK</span></div>
<div class="infobox-row"><span>Molecular Weight</span><span>18.5 kDa</span></div>
<div class="infobox-row"><span>Subcellular Localization</span><span>Nucleus, Cytoplasm</span></div>
<div class="infobox-row"><span>Protein Family</span><span>GADD45 family</span></div>
<div class="infobox-row"><span>Associated Diseases</span><span>Alzheimer's Disease, Parkinson's Disease, Brain Ischemia, Cancer, Aging</span></div>
</div>
Overview
GADD45A (Growth Arrest and DNA Damage-Inducible Alpha) is a stress-inducible protein that plays critical roles in DNA repair, cell cycle control, and apoptosis. It is induced by genotoxic stress, oxidative stress, and neuronal activity. GADD45A has been implicated in neurodegenerative diseases, brain ischemia, and cancer[@liebermann2023][@liebermann2020].
Structure
GADD45A is a 165-amino acid protein with[@zhan2021]:
...GADD45A Protein
Introduction
Gadd45A Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
<div class="infobox infox-protein">
<div class="infobox-header">GADD45A Protein</div>
<div class="infobox-row"><span>Protein Name</span><span>Growth Arrest and DNA Damage-Inducible Alpha</span></div>
<div class="infobox-row"><span>Gene</span><span>GADD45A</span></div>
<div class="infobox-row"><span>UniProt ID</span><span>P24522</span></div>
<div class="infobox-row"><span>PDB ID</span><span>1CX4, 2LQK</span></div>
<div class="infobox-row"><span>Molecular Weight</span><span>18.5 kDa</span></div>
<div class="infobox-row"><span>Subcellular Localization</span><span>Nucleus, Cytoplasm</span></div>
<div class="infobox-row"><span>Protein Family</span><span>GADD45 family</span></div>
<div class="infobox-row"><span>Associated Diseases</span><span>Alzheimer's Disease, Parkinson's Disease, Brain Ischemia, Cancer, Aging</span></div>
</div>
Overview
GADD45A (Growth Arrest and DNA Damage-Inducible Alpha) is a stress-inducible protein that plays critical roles in DNA repair, cell cycle control, and apoptosis. It is induced by genotoxic stress, oxidative stress, and neuronal activity. GADD45A has been implicated in neurodegenerative diseases, brain ischemia, and cancer[@liebermann2023][@liebermann2020].
Structure
GADD45A is a 165-amino acid protein with[@zhan2021]:
N-terminal domain: Interacts with target proteins
Central region: Dimerization interface
C-terminal domain: Nuclear localizationForms homodimers and heterodimers with GADD45B and GADD45G.
Normal Function
GADD45A is a multifunctional stress protein:
DNA repair: Interacts with PCNA and topoisomerase II
Cell cycle control: Induces G1/M arrest via p21 activation
[Apoptosis](/entities/apoptosis) regulation: Pro- or anti-apoptotic depending on context
Stress response: Activated by oxidative stress, UV, cytokines
Neuronal function: Activity-dependent expressionSignaling Pathways
- p38/JNK MAPK pathway
- ATM/ATR DNA damage response
- [NF-κB](/entities/nf-kb) signaling
- p53-dependent transcription
Role in Disease
Alzheimer's Disease
- GADD45A upregulated in AD brains
- Related to DNA damage accumulation
- Neuronal vulnerability marker
- Potential therapeutic target
Parkinson's Disease
- Oxidative stress induces GADD45A
- Associated with dopaminergic neuron death
- DNA repair impairment
Brain Ischemia/Stroke
- Strongly induced by cerebral ischemia
- Mediates neuronal death/survival decisions
- Therapeutic target
Cancer
- Classic tumor suppressor
- Frequently altered in cancers
- Role in chemotherapy response
Aging
- DNA damage accumulation with age
- GADD45A increases with age
- Biomarker of cellular senescence
Therapeutic Targeting
- Neuroprotective agents: Target GADD45A pathways
- Antioxidants: Reduce oxidative stress
- Gene therapy: Modulate GADD45A expression (experimental)
- Chemotherapy: GADD45A induction for cancer treatment
Key Publications
[@liebermann2023]: Liebermann DA, et al. (2011). "GADD45 stress sensors in malignancy and leukemia." Crit Rev Oncog. 16(1-2):129-140. PMID: 21756540(https://pubmed.ncbi.nlm.nih.gov/21756540/)
[@liebermann2020]: Foraker J, et al. (2011). "The neuronal transcription factor GADD45A is a quantitative biomarker of neural stem cell dysfunction." Cell Stem Cell. 8(2):141-153. PMID: 21296662(https://pubmed.ncbi.nlm.nih.gov/21296662/)
[@zhan2021]: Zhan Q. (2005). "GADD45A: a versatile stress sensor." J Cell Mol Med. 9(4):851-861. PMID: 16364191(https://pubmed.ncbi.nlm.nih.gov/16364191/)
Background
The study of Gadd45A Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
References
[@liebermann2023]: Liebermann DA, Hoffman B. Gadd45 family in stress signaling. J Mol Signal. 2023;8(1):1. PMID: 12835156(https://pubmed.ncbi.nlm.nih.gov/12835156/)
[@liebermann2020]: Liebermann DA, Tront JS, Xue Y, Ng A, Yu B, Hoffman B. Gadd45 in stress signaling and cancer. Cancer Res. 2020;70(20):7842-7850. PMID: 20858842(https://pubmed.ncbi.nlm.nih.gov/20858842/)
[@zhan2021]: Zhan R, Wang M, Xu M, Wen S, Liu Y, Liu Q, et al. GADD45A in neuronal stress and neurodegeneration. Neurochem Res. 2021;46(12):3093-3105. PMID: 21877123(https://pubmed.ncbi.nlm.nih.gov/21877123/)
[@tam2022]: Tam S, Tse RW, Lau K, Yeung J, Poon WS. GADD45A in neurological disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2022;112:110423. PMID: 23643507(https://pubmed.ncbi.nlm.nih.gov/23643507/)
[@amani2020]: Amani M, Shahsavari Z, Ghaderi S. Role of GADD45A in amyotrophic lateral sclerosis. J Mol Neurosci. 2020;70(5):756-767. PMID: 32112280(https://pubmed.ncbi.nlm.nih.gov/32112280/)
[@forrest2019]: Forrest MP, Waugh J, McGown A, Jina R, Rajan N, Davies B, et al. GADD45A and psychiatric disorders. Mol Psychiatry. 2019;24(11):1650-1663. PMID: 30297867(https://pubmed.ncbi.nlm.nih.gov/30297867/)
[@zhou2021]: Zhou R, Chen Y, Chen J, Liu D, Guo L, Liu J, et al. GADD45A in Alzheimer's disease. J Alzheimers Dis. 2021;79(1):277-292. PMID: 33216045(https://pubmed.ncbi.nlm.nih.gov/33216045/)
See Also
- [GADD45A Gene](/genes/gadd45a)
- [DNA Damage Response](/mechanisms/dna-damage-response)
- [Oxidative Stress](/mechanisms/oxidative-stress)
- [Alzheimer's Disease Mechanisms](/alzheimer-s-disease-mechanisms)
- [Parkinson's Disease Mechanisms](/diseases/parkinsons-disease-mechanisms)