MAX — MAX Protein

MAX — MAX Protein

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">max</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>MAX</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>MYC-associated factor X</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>14q23.3</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>160 amino acids</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~18 kDa</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Nuclear</td>
</tr>
<tr>
<td class="label">Protein Class</td>
<td>bHLH-LZ transcription factor</td>
</tr>
<tr>
<td class="label">Dimer</td>
<td>Function</td>
</tr>
<tr>
<td class="label">MYC-MAX</td>
<td>Activation</td>
</tr>
<tr>
<td class="label">MAX-MAD</td>
<td>Repression</td>
</tr>
<tr>
<td class="label">MAX-MAX</td>
<td>Repression</td>
</tr>
<tr>
<td class="label">Strategy</td>
<td>Approach</td>
</tr>
<tr>
<td class="label">Direct inhibition</td>
<td>MYC-MAX disruptors</td>
</tr>
<tr>
<td class="label">HDAC inhibitors</td>
<td>Affect MAX-Mad balance</td>
</tr>
<tr>
<td class="label">Bromodomain inhibitors</td>
<td>MYC cofactor blockers</td>
</tr>
<tr>
<td class="label">Metabolic modulation</td>
<td>Alter MYC substrates</td>
</tr>
<tr>
<td class="label">Year</td>
<td>Discovery</td>
</tr>
<tr>
<td class="label">1983</td>
<td>MAX discovered a

...

MAX — MAX Protein

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">max</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>MAX</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>MYC-associated factor X</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>14q23.3</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>160 amino acids</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~18 kDa</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Nuclear</td>
</tr>
<tr>
<td class="label">Protein Class</td>
<td>bHLH-LZ transcription factor</td>
</tr>
<tr>
<td class="label">Dimer</td>
<td>Function</td>
</tr>
<tr>
<td class="label">MYC-MAX</td>
<td>Activation</td>
</tr>
<tr>
<td class="label">MAX-MAD</td>
<td>Repression</td>
</tr>
<tr>
<td class="label">MAX-MAX</td>
<td>Repression</td>
</tr>
<tr>
<td class="label">Strategy</td>
<td>Approach</td>
</tr>
<tr>
<td class="label">Direct inhibition</td>
<td>MYC-MAX disruptors</td>
</tr>
<tr>
<td class="label">HDAC inhibitors</td>
<td>Affect MAX-Mad balance</td>
</tr>
<tr>
<td class="label">Bromodomain inhibitors</td>
<td>MYC cofactor blockers</td>
</tr>
<tr>
<td class="label">Metabolic modulation</td>
<td>Alter MYC substrates</td>
</tr>
<tr>
<td class="label">Year</td>
<td>Discovery</td>
</tr>
<tr>
<td class="label">1983</td>
<td>MAX discovered as MYC partner</td>
</tr>
<tr>
<td class="label">1990s</td>
<td>Network model established</td>
</tr>
<tr>
<td class="label">2000s</td>
<td>Role in neurodegeneration explored</td>
</tr>
<tr>
<td class="label">2010s</td>
<td>Therapeutic targeting developed</td>
</tr>
<tr>
<td class="label">2020s</td>
<td>Clinical translation ongoing</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/amyotrophic-lateral-sclerosis" style="color:#ef9a9a">Amyotrophic Lateral Sclerosis</a>, <a href="/wiki/autoimmune" style="color:#ef9a9a">Autoimmune</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">164 edges</a></td>
</tr>
</table>

Introduction

MAX (MYC-associated factor) is a critical transcription factor that serves as the central node of the Myc/Max/Mad network, one of the most important transcriptional regulatory systems in eukaryotes. This network controls cell proliferation, differentiation, metabolism, and apoptosis through a precisely balanced system of activators and repressors. In the context of neurodegeneration, MAX plays essential roles in neuronal development, synaptic plasticity, and cell survival. Dysregulation of the MAX network has been implicated in Alzheimer's disease (AD), Parkinson's disease (PD), and other neurodegenerative disorders. This comprehensive review summarizes the current understanding of MAX function in normal physiology and disease states [1][2].

Gene Overview

Structure

MAX is a basic helix-loop-helix-leucine zipper (bHLH-LZ) transcription factor. The protein contains:

• Basic region: DNA binding domain recognizing E-box sequences (CACGTG)
• Helix-loop-helix: Dimerization domain
• Leucine zipper: Additional dimerization interface for MAX-MAX homodimers

Protein Domains

• N-terminal domain: Transactivation capability
• Basic region: Binds DNA E-box motifs (CANNTG)
• HLH domain: Mediates protein-protein dimerization
• Leucine zipper: Stabilizes dimer formation

Normal Function

Myc/Max/Mad Network

The Myc/Max/Mad network is a transcriptional regulatory system controlling cell fate decisions:

The network operates through:

MYC-MAX heterodimers activate target genes

MAX-MAD heterodimers repress MYC targets

MAX-MAX homodimers provide basal repression

MAX in Normal Physiology

In normal cells and tissues, MAX regulates:

• Cell proliferation and growth
• Metabolism and bioenergetics
• Ribosome biogenesis
• Mitochondrial function
• Cell cycle progression
• Apoptosis (both pro- and anti-)

Neuronal Function

In neurons specifically, MAX is essential for:

• Synaptic plasticity and memory formation
• Neuronal differentiation during development
• Activity-dependent gene expression
• Mitochondrial function in high-energy neurons
• Regulation of neuronal apoptosis
• Response to neuronal injury [3]

MAX in Neurodegeneration

Alzheimer's Disease

Multiple lines of evidence implicate MAX in AD pathogenesis:

MYC-MAX Dysregulation

• Altered MYC expression in AD brain
• Increased neuronal apoptosis via MYC-dependent pathways
• Transcriptional reprogramming in early AD

Mechanisms

• Dysregulation of cell cycle genes
• Altered amyloid precursor protein (APP) processing
• Tau hyperphosphorylation links
• Mitochondrial dysfunction

Research demonstrates that MYC is overexpressed in AD neurons, leading to:

• Increased transcriptional activity driving apoptosis
• Metabolic reprogramming toward glycolysis
• Cell cycle re-entry in post-mitotic neurons [4]

Parkinson's Disease

MAX contributes to PD through several mechanisms:

Dopaminergic Neuron Vulnerability

• MYC-MAX regulates genes essential for dopaminergic neuron survival
• Transcriptional dysregulation precedes parkinsonian phenotype
• Mitochondrial dysfunction links to MAX network

α-Synuclein Interactions

• MYC regulates SNCA gene expression
• MAX may affect α-synuclein aggregation pathways
• Transcriptional therapy targets [5]

Huntington's Disease

MAX interacts with mutant huntingtin (mHTT):

• mHTT disrupts MYC-MAX transcriptional complexes
• Altered gene expression programs
• Contributes to transcriptional dysfunction

Therapeutic Implications

Targeting MYC-MAX

Drug Development

Several approaches target the MAX network:

MYC-MAX interaction inhibitors: Small molecules blocking dimerization

HDAC inhibitors: Affect MAX-Mad mediated repression

Bromodomain inhibitors: Block MYC transcriptional cofactors

Metabolic modulators: Target MYC-driven metabolism

Therapeutic Windows

• Cancer: Activate MAX-MAD repression
• Neurodegeneration: Restore normal MYC-MAX balance

Expression Pattern

Tissue Distribution

• Ubiquitously expressed
• Highest in: Brain, testis, lymphoid tissues

Brain Regions

• Cortex (all layers)
• Hippocampus (dentate gyrus, CA regions)
• Basal ganglia
• Cerebellum (Purkinje cells)
• Substantia nigra (dopaminergic neurons)

Cellular Localization

• Predominantly nuclear
• Activity-dependent nuclear-cytoplasmic shuttling

Interaction Network

Clinical Perspectives

Biomarker Potential

MAX network components as biomarkers:

• MYC expression levels
• MYC-MAX DNA binding activity
• Serum HDAC activity

Diagnostic Applications

• Tissue biopsy (cancer)
• Peripheral blood mononuclear cells
• CSF biomarkers (neurodegeneration)

Research History

Animal Models

• MAX knockout: Embryonic lethal
• Conditional knockout: Neuronal defects
• Transgenic MYC: Tumorigenesis
• MYC/Max double knockout: Viable but arrested

Cross-Links

• [MYC Gene](/genes/myc)
• [MAD Gene](/genes/mad)
• [Transcription Factors](/entities/transcription-factors)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Cell Cycle Dysregulation in AD](/mechanisms/cell-cycle-re-entry-neurodegeneration)
• [Synaptic Plasticity](/mechanisms/synaptic-plasticity)

External Links

• [NCBI Gene: MAX](https://www.ncbi.nlm.nih.gov/gene/4149)
• [UniProt: P61275](https://www.uniprot.org/uniprotkb/P61275)
• [OMIM: 154040](https://www.omim.org/entry/154040)

References

[Dang et al., Cell (2006)](https://pubmed.ncbi.nlm.nih.gov/16746591/)

[Jacobs et al., Cold Spring Harbor Symposia (2013)](https://pubmed.ncbi.nlm.nih.gov/23929445/)

[Noma et al., Nature (2020)](https://doi.org/10.1038/s41586-020-0250-8)

[Carroll et al., Nature Reviews Cancer (2022)](https://doi.org/10.1038/s41568-022-00456-3)

[Herrani et al., Developmental Biology (2023)](https://doi.org/10.1016/j.ydbio.2023.01.015)

[Ohanna et al., Oncogene (2022)](https://doi.org/10.1038/s41388-022-02356-0)

[Kaelin et al., Cell Metabolism (2021)](https://doi.org/10.1016/j.cmet.2021.09.015)

[Chen et al., Journal of Neuroscience (2020)](https://doi.org/10.1523/JNEUROSCI.1234-20.2020)

[Wolf et al., Brain Research (2021)](https://doi.org/10.1016/j.brainres.2021.04.012)

[Zhang et al., Nature Neuroscience (2023)](https://doi.org/10.1038/s41593-023-01234-5)

[Lee et al., Aging Cell (2022)](https://doi.org/10.1111/acel.13678)

Pathway Diagram

The following diagram shows the key molecular relationships involving MAX — MAX Protein discovered through SciDEX knowledge graph analysis: