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Target gene-independent functions of MYC oncoproteins

Apoorva Baluapuri1, Elmar Wolf1, Martin Eilers2

  • 1Theodor Boveri Institute, Department of Biochemistry and Molecular Biology, Biocenter, University of Würzburg, Am Hubland, Würzburg, Germany.

Nature Reviews. Molecular Cell Biology
|February 20, 2020
PubMed

Insights

MYC oncoproteins drive cancer by regulating gene transcription. New findings suggest MYC proteins promote transcription termination, enhancing cellular resilience and potentially driving tumorigenesis independently of target gene expression levels.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Genetics

Background:

  • MYC oncoproteins are key drivers of human tumorigenesis.
  • MYC proteins function as transcription factors, influencing gene expression.
  • Previous models proposed MYC's oncogenic activity through gene expression enhancement or repression.

Purpose of the Study:

  • To review the biochemistry of MYC proteins and their target genes.
  • To discuss recent advances in defining MYC and MYCN interactomes.
  • To explore mechanisms of MYC-mediated transcription modulation in tumorigenesis.

Main Methods:

  • Literature review of MYC protein biochemistry and target gene interactions.
  • Analysis of recent interactome studies for MYC and MYCN.
  • Synthesis of current understanding of MYC's role in transcription regulation.

Main Results:

  • MYC proteins promote transcription termination of RNA polymerase II, enhancing basal transcription stress resilience.
  • MYC proteins coordinate transcription elongation with DNA replication and cell cycle progression.
  • The mechanism of MYC-mediated transcription regulation may promote tumorigenesis independently of global or relative target gene expression changes.

Conclusions:

  • MYC proteins' role in transcription termination and coordination with cellular processes is crucial.
  • Tumorigenesis driven by MYC may involve mechanisms beyond simple target gene expression modulation.
  • Further research into MYC interactomes and transcription modulation is warranted.

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