A cell responds to pollutants - such as dioxin - via intricate and complex biochemical pathways beginning with the interaction of the pollutant molecule with a cell surface receptor. Christopher Bradfield and colleagues used yeast as a model system to elucidate the steps involved in the pathway that regulates vertebrate cell response to dioxin, the aryl hydrocarbon receptor (AHR) signal transduction pathway. To assess the molecules and pathways involved in the AHR pathway, the research group studied 4507 yeast "deletion" strains, each strain missing one gene from its genome. In this way Bradfield and colleagues identified 54 genes that had a significant influence on AHR response. Only two of these genes, termed modifiers, had been previously identified.

Though yeast does not naturally possess AHR, it is an ideal genetic model due to its small, well-characterized genome and similarity to vertebrate systems. Because yeast have been so well studied, the researchers were able to construct a "protein interaction network," (PIN) based on previously known interactions between the proteins encoded by the 54 modifier genes. The resulting map revealed groups of highly connected, related modifiers. The authors show that these modifiers group into five discrete biochemical steps in the pathway of dioxin signaling. Not only did they succeed in identifying potentially new genes involved in the signaling pathway but they were able to identify one of the modules as a previously undescribed nuclear step in the signaling pathway.

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Contact: Christopher Bradfield
Bradfield@oncology.wisc.edu
608-262-2024
Public Library of Science
16-Mar-2004

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