The Aryl-Hydrocarbon Receptor Protein Interaction Network (AHR-PIN) as Identified by Tandem Affinity Purification (TAP) and Mass Spectrometry.
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.
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824-1319, USA ; Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824-1319, USA.
Dorothy M
DM
Tappenden
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824-1319, USA ; Center for Mitochondrial Science and Medicine, Michigan State University, East Lansing, MI 48824-1319, USA.
Hye Jin
HJ
Hwang
The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, USA.
Longlong
L
Yang
The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, USA.
Russell S
RS
Thomas
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824-1319, USA ; Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824-1319, USA ; Center for Mitochondrial Science and Medicine, Michigan State University, East Lansing, MI 48824-1319, USA.
John J
JJ
Lapres