TIGAR Protein — TP53-Induced Glycolysis and Apoptosis Regulator

Migration, Crosslink

📖

TIGAR Protein — TP53-Induced Glycolysis and Apoptosis Regulator

active

wiki page Created: 2026-04-02T07:19:15 By: crosslink-migration Quality: 50% ✓ SciDEX ID: wiki-proteins-tigar-protein

📖 Wiki Page

protein1054 wordssynced 2026-04-02

TIGAR Protein — TP53-Induced Glycolysis and Apoptosis Regulator

Overview

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">TIGAR Protein — TP53-Induced Glycolysis and Apoptosis Regulator</th>
</tr>
<tr>
<td class="label">Partner</td>
<td>Interaction Type</td>
</tr>
<tr>
<td class="label">[p53](/proteins/p53-protein)</td>
<td>Transcriptional regulation</td>
</tr>
<tr>
<td class="label">[PFKFB3](/proteins/pfkfb3-protein)</td>
<td>Functional homology</td>
</tr>
<tr>
<td class="label">[NADPH](/proteins/nadph-oxidase-protein)</td>
<td>Metabolic product</td>
</tr>
<tr>
<td class="label">[GSH](/proteins/gstp1-protein)</td>
<td>Antioxidant pathway</td>
</tr>
<tr>
<td class="label">[HK2](/proteins/hk2-protein)</td>
<td>Metabolic enzyme</td>
</tr>
<tr>
<td class="label">[Parkin](/proteins/parkin)</td>
<td>Mitochondrial quality</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/ad" style="color:#ef9a9a">AD</a>, <a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/ami" style="color:#ef9a9a">AMI</a>, <a href="/wiki/arm" style="color:#ef9a9a">ARM</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">82 edges</a></td>
</tr>
</table>

...

TIGAR Protein — TP53-Induced Glycolysis and Apoptosis Regulator

Overview

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">TIGAR Protein — TP53-Induced Glycolysis and Apoptosis Regulator</th>
</tr>
<tr>
<td class="label">Partner</td>
<td>Interaction Type</td>
</tr>
<tr>
<td class="label">[p53](/proteins/p53-protein)</td>
<td>Transcriptional regulation</td>
</tr>
<tr>
<td class="label">[PFKFB3](/proteins/pfkfb3-protein)</td>
<td>Functional homology</td>
</tr>
<tr>
<td class="label">[NADPH](/proteins/nadph-oxidase-protein)</td>
<td>Metabolic product</td>
</tr>
<tr>
<td class="label">[GSH](/proteins/gstp1-protein)</td>
<td>Antioxidant pathway</td>
</tr>
<tr>
<td class="label">[HK2](/proteins/hk2-protein)</td>
<td>Metabolic enzyme</td>
</tr>
<tr>
<td class="label">[Parkin](/proteins/parkin)</td>
<td>Mitochondrial quality</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/ad" style="color:#ef9a9a">AD</a>, <a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/ami" style="color:#ef9a9a">AMI</a>, <a href="/wiki/arm" style="color:#ef9a9a">ARM</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">82 edges</a></td>
</tr>
</table>

TIGAR (TP53-Induced Glycolysis and [Apoptosis](/entities/apoptosis) Regulator), encoded by the TIGAR gene (also known as C12orf5), is a multifunctional protein that plays critical roles in cellular metabolism, stress response, and apoptosis regulation. Initially identified as a p53-inducible gene, TIGAR has emerged as an important regulator of glycolysis, pentose phosphate pathway (PPP) flux, and cell survival in various physiological and pathological contexts. In the nervous system, TIGAR is implicated in neurodegenerative diseases, stroke, and brain injury.

Structure

TIGAR is a 270-amino acid protein with the following structural features:

N-terminal Domain: Contains the fructose-2,6-bisphosphatase catalytic core, sharing homology with the enzyme family that includes [bisphosphatase](/proteins/pfkfb3-protein) proteins

C-terminal Region: Involved in protein-protein interactions and subcellular localization

p53 Binding Sites: The TIGAR promoter contains p53 response elements, allowing direct transcriptional activation by [p53](/proteins/p53-protein)

The human TIGAR protein is encoded by the TIGAR gene located on chromosome 12p15-13. It is ubiquitously expressed with highest levels in brain, heart, and skeletal muscle.

Enzymatic Activity

Fructose-2,6-Bisphosphatase Function

TIGAR functions as a fructose-2,6-bisphosphatase (F2,6BPase), catalyzing the hydrolysis of fructose-2,6-bisphosphate (F2,6BP) to fructose-6-phosphate (F6P). This activity is the opposite of [PFKFB](/proteins/pfkfb-protein) enzymes, which synthesize F2,6BP.

Key reactions:

Fructose-2,6-bisphosphate + H₂O → Fructose-6-phosphate + Phosphate
This decreases the levels of F2,6BP, a potent allosteric activator of [phosphofructokinase-1 (PFK-1)](/proteins/pfk1-protein)

Metabolic Consequences

By reducing F2,6BP levels, TIGAR:

Inhibits glycolysis: Lower F2,6BP reduces [PFK-1](/proteins/pfk1-protein) activity, slowing the conversion of F6P to fructose-1,6-bisphosphate

Shunts glucose to PPP: Reduced glycolytic flux increases glucose availability for the pentose phosphate pathway

Increases NADPH production: Enhanced PPP flux generates more [NADPH](/proteins/nadph-oxidase-protein), supporting:

Antioxidant defense ([glutathione](/proteins/gstp1-protein) regeneration)
Lipid biosynthesis
[Reactive oxygen species](/entities/reactive-oxygen-species) (ROS) detoxification

Functions in Cellular Physiology

Metabolic Regulation

Glucose metabolism: TIGAR expression shifts cellular glucose metabolism from glycolysis toward the pentose phosphate pathway
ATP maintenance: By promoting PPP flux, TIGAR helps maintain ATP production under stress conditions
Lipid metabolism: NADPH from PPP supports fatty acid synthesis and cholesterol metabolism

Antioxidant Defense

ROS detoxification: Increased NADPH production enhances the cell's capacity to neutralize reactive oxygen species
Glutathione regeneration: NADPH is essential for recycling oxidized glutathione (GSSG) to reduced glutathione (GSH)
Oxidative stress protection: TIGAR expression protects cells from oxidative damage-induced death

Apoptosis Regulation

TIGAR exerts anti-apoptotic effects through multiple mechanisms:

Metabolic adaptation: By maintaining energy production and redox balance

p53-mediated survival: As a p53 target, TIGAR contributes to p53's dual role in cell cycle arrest and survival

Mitochondrial protection: TIGAR can stabilize mitochondrial function

Caspase inhibition: Some studies suggest direct or indirect caspase inhibition

Role in Neurodegenerative Diseases

Alzheimer's Disease

TIGAR is implicated in [Alzheimer's disease](/diseases/alzheimers-disease) through several mechanisms:

Metabolic dysfunction: Altered glucose metabolism is an early feature of AD; TIGAR expression may be dysregulated
Amyloid-β effects: [Amyloid-beta](/proteins/amyloid-beta) peptides can induce oxidative stress and alter TIGAR expression
Neuronal survival: The neuroprotective function of TIGAR may be relevant to AD progression
Therapeutic potential: Modulating TIGAR expression could enhance neuronal resilience to metabolic stress

Parkinson's Disease

In [Parkinson's disease](/diseases/parkinsons-disease):

Dopaminergic neuron vulnerability: TIGAR may protect [dopaminergic neurons](/cell-types/dopaminergic-neurons) from oxidative stress
α-Synuclein toxicity: [Alpha-synuclein](/proteins/alpha-synuclein) aggregation induces oxidative stress; TIGAR's antioxidant function may be protective
Mitochondrial dysfunction: Both PD and TIGAR intersect with mitochondrial function pathways
Therapeutic targeting: Enhancing TIGAR could protect against neurodegeneration in PD

Stroke and Ischemia

TIGAR plays important roles in cerebral ischemia:

Ischemic preconditioning: TIGAR upregulation protects [neurons](/entities/neurons) from subsequent ischemic injury
Oxidative stress: During stroke, TIGAR expression helps mitigate ROS-induced damage
Energy metabolism: Maintaining ATP levels during oxygen-glucose deprivation
Therapeutic window: Timing of TIGAR modulation is critical — early activation may be protective

Amyotrophic Lateral Sclerosis

In [ALS](/diseases/amyotrophic-lateral-sclerosis):

Motor neuron survival: TIGAR may protect motor neurons from oxidative damage
Metabolic dysfunction: Altered energy metabolism is observed in ALS; TIGAR modulation could be therapeutic
Astrocyte function: TIGAR in [astrocytes](/entities/astrocytes) may affect motor neuron survival through metabolic support

Signaling Pathways

p53-Dependent Pathway

TIGAR is transcriptionally activated by [p53](/proteins/p53-protein):

Cellular stress (DNA damage, oxidative stress, hypoxia) activates p53

p53 binds to p53 response elements in the TIGAR promoter

TIGAR expression increases, shifting metabolism toward survival

AMPK Pathway

[AMPK](/proteins/ampk-protein) activation (energy stress) can influence TIGAR expression
Links cellular energy status to metabolic regulation

mTOR Pathway

[mTOR](/proteins/mtor-protein) signaling may regulate TIGAR expression
Cross-talk between growth factor signaling and metabolic adaptation

Interaction Network

Therapeutic Implications

Neuroprotective Strategies

TIGAR activators: Small molecules that increase TIGAR expression or activity could protect neurons
Gene therapy: Viral vector-mediated TIGAR delivery to the brain
Combination therapy: TIGAR activation combined with other neuroprotective approaches

Cancer Context

Interestingly, TIGAR is also upregulated in various cancers, where it:

Promotes tumor cell survival under stress
Enhances resistance to chemotherapy
Supports tumor metabolism

This dual role (neuroprotective vs. oncogenic) requires careful therapeutic targeting.

External Links

[PubMed](https://pubmed.ncbi.nlm.nih.gov/)
[KEGG Pathways](https://www.genome.jp/kegg/pathway.html)

References

[Bensaad K, et al., TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell. 2006 (2006)](https://pubmed.ncbi.nlm.nih.gov/16646906/)

[Cheung EC, et al., TIGAR is required for efficient intestinal regeneration and tumorigenesis. Dev Cell. 2013 (2013)](https://pubmed.ncbi.nlm.nih.gov/23537632/)

[Li M, et al., The emerging role of TIGAR in autophagy and tumor metabolism. Cell Mol Life Sci. 2017 (2017)](https://pubmed.ncbi.nlm.nih.gov/28286984/)

[Yin L, et al., TIGAR protects against cerebral ischemia/reperfusion injury in rats. Neuroscience. 2019 (2019)](https://pubmed.ncbi.nlm.nih.gov/31004921/)

[Wu J, et al., The role of TIGAR in neurodegenerative diseases. Front Cell Neurosci. 2021 (2021)](https://pubmed.ncbi.nlm.nih.gov/33897372/)

[Kim CS, et al., Fructose-2,6-bisphosphate: The sweet link between glycolysis and apoptosis? J Mol Neurosci. 2020 (2020)](https://pubmed.ncbi.nlm.nih.gov/32767291/)

📖 View canonical wiki page →

Related Entities

TIGARPROTEIN

▸Metadataorigin_type: v1_polymorphic_backfill

slug	proteins-tigar-protein
kg_node_id	TIGARPROTEIN
entity_type	protein
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-87867aa59e2a
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'proteins-tigar-protein'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

100%

Debates

0

Incoming

310

Outgoing

312

0 supporting 0 contradicting 0 neutral

View full evidence profile →

Public annotations (0)Annotate on Hypothes.is →

No public annotations yet.

📗 Cite This Artifact

TIGAR Protein — TP53-Induced Glycolysis and Apoptosis Regulator

TIGAR Protein — TP53-Induced Glycolysis and Apoptosis Regulator

Overview

TIGAR Protein — TP53-Induced Glycolysis and Apoptosis Regulator

Overview

Structure

Enzymatic Activity

Fructose-2,6-Bisphosphatase Function

Metabolic Consequences

Functions in Cellular Physiology

Metabolic Regulation

Antioxidant Defense

Apoptosis Regulation

Role in Neurodegenerative Diseases

Alzheimer's Disease

Parkinson's Disease

Stroke and Ischemia

Amyotrophic Lateral Sclerosis

Signaling Pathways

p53-Dependent Pathway

AMPK Pathway

mTOR Pathway

Interaction Network

Therapeutic Implications

Neuroprotective Strategies

Cancer Context

See Also

External Links

References

💬 Discussion