The MYC family: three genes, one master switch for growth

Tags: gene families, transcription factors, neuroblastoma, MYCN

They switch on growth. They are amplified in tumours. And for decades they were called undruggable.

Few gene families are as closely tied to cancer as the MYC family. Its three members, MYC, MYCN and MYCL, encode transcription factors that tell a cell when to grow, divide and build the biomass to do so. When that signal gets stuck on, the consequences are severe.

What the MYC proteins do

All three share a basic helix-loop-helix leucine zipper (bHLH-LZ) domain. To work, they pair up with a partner protein called MAX, and the MYC–MAX dimer binds E-box sequences (CACGTG) in DNA. From there it regulates a large programme of genes involved in ribosome biogenesis, metabolism, protein synthesis and cell cycle progression. MYC is less a single-target switch than an amplifier of the cell’s existing growth programme.

Three siblings, three territories

  • MYC is broadly expressed in proliferating cells and is deregulated in many cancer types. A classic example is the translocation that places MYC under an immunoglobulin enhancer in Burkitt lymphoma.
  • MYCN is mainly expressed during development, especially in the nervous system. In neuroblastoma, MYCN amplification occurs in roughly one in five tumours and marks high-risk disease.
  • MYCL has a more restricted pattern and is best known for amplification in small cell lung cancer.


Why “undruggable”?

MYC proteins have no obvious pocket for a small molecule to bind, and they act mainly through protein–DNA and protein–protein interactions. Research has therefore turned to indirect strategies: destabilising the protein, blocking MYC–MAX dimerisation, targeting its cofactors, and exploiting the vulnerabilities that MYC-driven cells depend on. Whether a target is actionable is exactly the question R2’s Target Actionability Reviews were built to help answer. TARs

Exploring the MYC family in R2

  • YY-plot: plot MYCN across a neuroblastoma cohort and see every sample ranked from lowest to highest expression, which makes the amplified tumours stand out immediately.
  • Compare cancer types: look at MYC and MYCL expression across the TCGA cancer types in R2.
  • Cell line models: check MYCN status and expression in the classical neuroblastoma cell lines from our multi-omics resource.
  • Your own data: upload your dataset and see how the MYC family behaves in your own cohort.

Try it yourself

Pick a family member, pick a dataset, and see what its expression landscape looks like. Which gene family should we cover next? Let us know in the comments.

Explore the data at r2platform.com.

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