The MAX gene in humans encodes the MAX transcription factor, which is crucial for various cellular processes. It belongs to the basic helix-loop-helix leucine zipper (bHLHZ) family of transcription factors. The MAX protein forms homodimers with itself and heterodimers with other transcription factors like Myc, Mad, Mxl1, and Mxd proteins .
The MAX transcription factor plays a significant role in regulating gene expression by forming dimers that bind to specific DNA sequences known as E-boxes. These dimers can either activate or repress gene transcription, depending on the composition of the dimer. For instance, the Myc/Max heterodimer is involved in promoting cell proliferation, while the Mad/Max heterodimer can induce apoptosis .
The MAX gene has been implicated in several diseases. Mutations in the MAX gene have been associated with hereditary pheochromocytoma and small cell lung cancer (SCLC). In SCLC, mutations in MAX are mutually exclusive with alterations in Myc and BRG1, suggesting a complex interplay between these genes in cancer development .
Recent studies have focused on modulating MAX dimerization as a therapeutic strategy. For example, the compound KI-MS2-008 has been identified as a small molecule that stabilizes the MAX homodimer, reducing Myc protein levels and Myc-regulated transcripts. This approach shows promise in suppressing cancer cell growth and tumor formation .
Understanding the role of MAX in transcriptional regulation and its interactions with other proteins can provide insights into developing targeted therapies for diseases involving MAX dysregulation. Further research is needed to explore the full potential of modulating MAX dimerization in a clinical context.
| Interacting Protein | Function |
|---|---|
| Myc | Promotes cell proliferation |
| Mad | Induces apoptosis |
| Mxl1 | Forms heterodimers with MAX |
| Mxd proteins | Competes with Myc for MAX binding |
| MNT | Transcriptional repressor |
| MSH2 | DNA mismatch repair protein |
| MXD1 | Transcriptional repressor |
| MXI1 | Transcriptional repressor |
| MYCL1 | Myc-like protein |
| N-Myc | Neuroblastoma-derived Myc protein |
| SPAG9 | Sperm-associated antigen 9 |
| TEAD1 | Transcriptional enhancer factor |
MAX (gene) - Wikipedia. Available at: https://en.wikipedia.org/wiki/MAX_(gene)
Stabilization of the Max Homodimer with a Small Molecule. Available at: https://pubmed.ncbi.nlm.nih.gov/30880155/
The MAX gene (myc-associated factor X) encodes the MAX transcription factor in humans. This protein contains basic helix-loop-helix and leucine zipper motifs, placing it in the bHLHZ family of transcription factors .
Methodological approach:
Researchers studying MAX typically employ a combination of techniques:
Chromatin immunoprecipitation (ChIP) to identify DNA binding patterns
Co-immunoprecipitation to detect protein-protein interactions
Gene expression analysis following MAX manipulation
Structural biology approaches to characterize binding domains
MAX functions by forming homodimers with other MAX proteins or heterodimers with transcription factors including Mad, Mxl1, and Myc. These dimers compete for binding to E-box sequences in gene promoters, creating a sophisticated regulatory system affecting diverse gene targets .
MAX engages in multiple protein interactions that collectively regulate gene transcription through competitive binding mechanisms.
Methodological approach:
To identify and characterize these interactions, researchers should:
Employ proteomics approaches including mass spectrometry
Conduct sequential ChIP experiments to determine co-occupancy
Use fluorescence-based interaction assays in live cells
Perform domain mapping to identify critical interaction surfaces
Research findings demonstrate that MAX interacts with numerous proteins including:
Myc family proteins (c-Myc, N-Myc, MYCL1)
MNT and MXD1 transcriptional regulators
MSH2 DNA repair protein
MXI1 transcriptional repressor
SPAG9 scaffold protein
TEAD1 transcription factor
These interactions regulate transcription through competition for MAX binding, differential cofactor recruitment, and altered DNA binding specificity. The rearrangement of dimers (switching between Mad:Max, Max:Myc, etc.) enables precise control over diverse gene expression programs .
MAX gene mutations play significant roles in multiple cancer types, particularly hereditary pheochromocytoma and small cell lung cancer (SCLC), through distinct molecular mechanisms.
Methodological approach:
Investigating MAX's role in cancer requires integrated approaches:
Whole-genome or targeted sequencing of patient samples
CRISPR-engineered cell lines modeling specific mutations
Patient-derived xenografts for in vivo studies
Transcriptome and proteome profiling before/after MAX restoration
Research findings indicate that:
In hereditary pheochromocytoma, MAX mutations act as tumor suppressor mutations
In SCLC, MAX gene inactivation occurs mutually exclusively with alterations in MYC and BRG1 genes
BRG1 regulates MAX expression through direct recruitment to the MAX promoter region
Depletion of BRG1 significantly impairs growth specifically in MAX-deficient cells, creating a synthetic lethal interaction
| Genetic Alteration | Cancer Type | Mutual Exclusivity | Functional Consequence |
|---|---|---|---|
| MAX inactivation | SCLC | Mutually exclusive with MYC and BRG1 alterations | Disrupts transcriptional regulation |
| MAX mutation | Pheochromocytoma | N/A | Acts as tumor suppressor |
| BRG1 depletion in MAX-deficient cells | SCLC | Creates synthetic lethality | Severely impairs cell growth |
Studying MAX's opposing roles in cell proliferation and apoptosis requires sophisticated approaches that can distinguish between these cellular outcomes.
Methodological approach:
Researchers should consider:
Temporal gene expression systems:
Inducible MAX expression (Tet-On/Off)
Time-course transcriptomics
Pulse-chase experiments tracking protein dynamics
Functional genomics approaches:
CRISPR-engineered MAX variants
Pooled genetic screens identifying synthetic interactions
Systematic partner protein manipulation
Single-cell techniques:
scRNA-seq to capture transcriptional heterogeneity
Live-cell imaging with proliferation/apoptosis reporters
Mass cytometry for multi-parameter cellular analysis
Research findings demonstrate that MAX homodimers and different heterodimers can promote either cell proliferation or apoptosis depending on cellular context and available partners . MAX must dimerize to be biologically active, and its transcriptionally active forms can drive opposing cellular fates, highlighting the need for context-specific experimental designs.
Anthropomorphization involves attributing human characteristics and social roles to AI technologies, significantly influencing how they are integrated into organizational settings.
Methodological approach:
Researchers should employ:
Semi-structured interviews capturing language used to describe AI
Ethnographic observation of human-AI interactions
Discourse analysis examining pronoun usage and descriptions
Analysis of written and verbal communications about AI systems
Research findings from a workplace case study of an anthropomorphized AI called "Max" reveal:
Managers referred to Max using human terms like "junior colleague," "team member," and attributed learning capabilities: "He is learning"
Employees also anthropomorphized Max but with more negative human attributes: "Max is quite stupid," "a beginner," "needing supervision"
Anthropomorphization occurred despite Max being merely "an algorithm without physical or visual form"
This anthropomorphization creates expectations that influence technology adoption and can amplify existing organizational dynamics.
Organizational hierarchy significantly shapes how individuals perceive and interact with AI systems, creating distinct patterns of engagement and resistance.
Methodological approach:
To investigate this phenomenon, researchers should:
Conduct comparative analysis across organizational tiers
Employ power-sensitive research designs
Analyze decision-making processes about AI implementation
Examine resource allocation for AI training and integration
Research findings demonstrate clear hierarchical differences:
Managers viewed AI positively, focusing on future potential: "Max is our junior colleague. He does these [booking] tasks faster. And our employees can do something else in the meantime"
Employees emphasized present limitations: "Max is quite stupid, and he is just a beginner"
Managers expressed frustration with employee resistance: "I'm amazed that people just won't do this small thing"
Employees asserted their expertise: "We are knowledgeable and can recommend how to work with robots"
These hierarchical differences create fundamental tensions in AI implementation that require careful management and inclusive design processes.
Understanding collective affects around anthropomorphized AI requires sophisticated frameworks that capture the interplay between technology, human emotions, and organizational dynamics.
Methodological approach:
Researchers should consider:
Affect theory frameworks:
Concepts like "affective atmospheres" and "circulation"
Tracking affects across organizational boundaries
Analyzing non-verbal emotional expressions
Socio-material theoretical approaches:
Actor-network theory for human-AI assemblages
Boundary object analysis of AI mediation
Material agency alongside human agency
Longitudinal research designs:
Tracking affective shifts through implementation phases
Analyzing critical incidents and turning points
Documenting evolving anthropomorphization practices
Research findings from the Max case study led to the conceptualization of a "circle of mixed collective affects" where "human affects were extended to include an artificially intelligent 'colleague'" . This theoretical innovation explains how affectively charged organizational groups extend affects to include affectively inert technology, creating group-level patterns that transcend individual responses.
AI systems frequently function as amplifiers of pre-existing organizational tensions rather than simply creating new conflicts, requiring specialized methodologies to capture this amplification effect.
Methodological approach:
Effective research designs include:
Pre-post implementation comparative analyses
Multi-stakeholder tension mapping across organizational levels
Critical discourse analysis of communications about AI systems
Process tracing methodologies documenting tension amplification
Research findings demonstrate how the AI system "Max" amplified pre-existing tensions:
Researchers identified conflicts between managers and employees that predated AI implementation
The AI system made these tensions more visible: "conflicts... were hidden from view"
Max became a focal point for expressing broader dissatisfaction: "Now, with the introduction of all these Maxes, our voices need to be heard"
| Analytical Category | Inductively Generated Meanings | Hermeneutic Principles Application | Cross-checking | Researcher Reflexivity |
|---|---|---|---|---|
| AI as amplifier of human discontent | Managers and employees expressed different views of Max, reflecting deeper organizational conflicts | Initially hidden tensions became visible through discussions about Max | Expanded analysis to include views across management levels | Team discussions about interpretations of circulating affects |
By conceptualizing AI as an "amplifier of human discontent," researchers can better understand how these technologies surface and intensify existing organizational tensions .
MAX contains a basic helix-loop-helix (bHLH) domain, which is essential for its function as a transcription factor. This domain allows MAX to form homodimers and heterodimers with other family members, including Mad, Mxi1, and Myc . The protein is highly conserved across species, indicating its fundamental role in cellular processes.
MAX primarily functions as a transcriptional regulator. It forms dimers that bind to specific DNA sequences known as E-boxes, influencing the transcription of target genes . The interaction between MAX and Myc is particularly significant, as Myc is an oncoprotein involved in cell proliferation, differentiation, and apoptosis . By forming heterodimers with Myc, MAX modulates the transcriptional activity of Myc, thereby impacting various cellular processes.
The homodimers and heterodimers formed by MAX compete for binding to E-box sequences in the DNA . This competition creates a complex system of transcriptional regulation, where the balance between different dimer forms determines the transcriptional outcome. Additionally, MAX may repress transcription by recruiting chromatin remodeling complexes that contain histone methyltransferase activity .
The activity of MAX is regulated at multiple levels, including its expression, dimerization, and interaction with other proteins. Unlike Myc, which is tightly regulated throughout the cell cycle, MAX is relatively stable and abundant . This stability allows MAX to serve as a consistent regulatory partner for Myc and other bHLHZ family members.
Recombinant human MAX protein is typically produced in Escherichia coli (E. coli) or baculovirus-insect cells . The recombinant protein is often fused with tags such as polyhistidine or GST to facilitate purification. These recombinant forms are used in various research applications to study the function and regulation of MAX.