The aryl hydrocarbon receptor regulates nucleolar activity and protein synthesis in MYC-expressing cells

Genes Dev. 2018 Oct 1;32(19-20):1303-1308. doi: 10.1101/gad.313007.118. Epub 2018 Sep 25.

Abstract

MYC enhances protein synthesis by regulating genes involved in ribosome biogenesis and protein translation. Here, we show that MYC-induced protein translation is mediated by the transcription factor aryl hydrocarbon receptor (AHR), which is induced by MYC in colonic cells. AHR promotes protein synthesis by activating the transcription of genes required for ribosome biogenesis and protein translation, including OGFOD1 and NOLC1. Using surface sensing of translation (SUnSET) to measure global protein translation, we found that silencing AHR or its targets diminishes protein synthesis. Therefore, targeting AHR or its downstream pathways could provide a novel approach to limit biomass production in MYC-driven tumors.

Keywords: AHR; Myc; aryl hydrocarbon receptor; cancer; nucleolus; ribosome biogenesis; transcription; translation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Nucleolus / genetics
  • Cell Nucleolus / metabolism*
  • Cells, Cultured
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Humans
  • Protein Biosynthesis*
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Rats
  • Receptors, Aryl Hydrocarbon / biosynthesis
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / physiology*
  • Transcriptional Activation

Substances

  • Proto-Oncogene Proteins c-myc
  • Receptors, Aryl Hydrocarbon