Role of the aryl hydrocarbon receptor in cell cycle regulation

Alvaro Puga, Jennifer Marlowe, Sonya Barnes, Ching Yi Chang, Andrew Maier, Zongqing Tan, J. Kevin Kerzee, Xaoqing Chang, Matt Strobeck, Erik S. Knudsen

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

One of the most puzzling aspects of the biological impact of polycyclic aromatic hydrocarbon compounds is that they elicit an apparently unrelated variety of toxic, teratogenic, and carcinogenic responses in exposed animals and in humans. At the cellular level, these environmental toxicants affect cell cycle regulatory mechanisms and signal transduction pathways in ways that are equally diverse and often contradictory. For example, depending on the particular cell lines studied, exposure to these compounds may lead to cell proliferation, to terminal differentiation, or to apoptosis. These effects are mediated by the aryl hydrocarbon receptor, a ligand-activated transcription factor well known for its regulatory activity on the expression of several phase I detoxification cytochrome P450 genes. Research into the molecular mechanisms of aryl hydrocarbon receptor function has uncovered a novel role for this protein during cell cycle progression. The activated receptor acts as an environmental sensor and cell cycle checkpoint that commits cells exposed to adverse environmental stimuli to arrest before the onset of DNA replication.

Original languageEnglish (US)
Pages (from-to)171-177
Number of pages7
JournalToxicology
Volume181-182
DOIs
StatePublished - Dec 27 2002

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Keywords

  • Aromatic hydrocarbon receptor
  • Cell cycle
  • E2F
  • Environmental sensors
  • Protein interactions
  • Retinoblastoma

ASJC Scopus subject areas

  • Toxicology

Cite this

Puga, A., Marlowe, J., Barnes, S., Chang, C. Y., Maier, A., Tan, Z., Kerzee, J. K., Chang, X., Strobeck, M., & Knudsen, E. S. (2002). Role of the aryl hydrocarbon receptor in cell cycle regulation. Toxicology, 181-182, 171-177. https://doi.org/10.1016/S0300-483X(02)00276-7