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Journal of Toxicology
Volume 2013 (2013), Article ID 279829, 12 pages
Research Article

The Aryl-Hydrocarbon Receptor Protein Interaction Network (AHR-PIN) as Identified by Tandem Affinity Purification (TAP) and Mass Spectrometry

1Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824-1319, USA
2Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824-1319, USA
3Center for Mitochondrial Science and Medicine, Michigan State University, East Lansing, MI 48824-1319, USA
4The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, USA

Received 2 August 2013; Revised 9 October 2013; Accepted 14 October 2013

Academic Editor: Robert Tanguay

Copyright © 2013 Dorothy M. Tappenden et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The aryl-hydrocarbon receptor (AHR), a ligand activated PAS superfamily transcription factor, mediates most, if not all, of the toxicity induced upon exposure to various dioxins, dibenzofurans, and planar polyhalogenated biphenyls. While AHR-mediated gene regulation plays a central role in the toxic response to dioxin exposure, a comprehensive understanding of AHR biology remains elusive. AHR-mediated signaling starts in the cytoplasm, where the receptor can be found in a complex with the heat shock protein of 90 kDa (Hsp90) and the immunophilin-like protein, aryl-hydrocarbon receptor-interacting protein (AIP). The role these chaperones and other putative interactors of the AHR play in the toxic response is not known. To more comprehensively define the AHR-protein interaction network (AHR-PIN) and identify other potential pathways involved in the toxic response, a proteomic approach was undertaken. Using tandem affinity purification (TAP) and mass spectrometry we have identified several novel protein interactions with the AHR. These interactions physically link the AHR to proteins involved in the immune and cellular stress responses, gene regulation not mediated directly via the traditional AHR:ARNT heterodimer, and mitochondrial function. This new insight into the AHR signaling network identifies possible secondary signaling pathways involved in xenobiotic-induced toxicity.