Role of the aryl hydrocarbon receptor in cell cycle regulation.
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.
Puga
Alvaro
A
Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, 123 E. Shields Street, Cincinnati, OH 45267-0056, USA. alvaro.puga@uc.edu
Marlowe
Jennifer
J
Barnes
Sonya
S
Chang
Ching-yi
CY
Maier
Andrew
A
Tan
Zongqing
Z
Kerzee
J Kevin
JK
Chang
Xaoqing
X
Strobeck
Matt
M
Knudsen
Erik S
ES
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D017936:Cytochrome a Group / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D004785:Environmental Pollutants / Q000633:toxicity; D006801:Humans; D008024:Ligands; D010957:Plasmids / Q000235:genetics; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000502:physiology*; D016160:Retinoblastoma Protein / Q000502:physiology
D017936:Cytochrome a Group; D004785:Environmental Pollutants; D008024:Ligands; D011084:Polycyclic Aromatic Hydrocarbons; D018336:Receptors, Aryl Hydrocarbon; D016160:Retinoblastoma Protein