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The aryl hydrocarbon receptor forms a complex with cyclin-dependent kinase-2 as a function of cell cycle.

The aryl hydrocarbon receptor (AhR) is a soluble receptor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent and persistent environmental pollutant. Numerous studies demonstrate that expo-sure to TCDD elicits a G1 cell cycle arrest. The G1/S phase transition is regulated by cyclin-dependent kinases (CDK) that phosphorylate retinoblastoma protein (Rb) to allow S-phase progression. We have previously shown that TCDD treatment suppresses CDK2 activity and decreases formation of CDK2/cyclin E complexes. Both CDK2 and AhR contain LXCXE binding motifs used for protein-protein interactions, which prompted us to investigate a possible association between these proteins. Rat hepatoma cells (5L) were serum starved for 24 hours and released in the presence of TCDD (10 nM) or vehicle (DMSO). Using coimmunoprecpitation and western blotting, we found an association between CDK2 and AhR in vehicle-treated cells 24 hours after serum release, whereas this interaction was completely abolished by TCDD treatment. We propose that the AhR-CDK2 complex functions as a scaffold for additional cell cycle proteins such as cyclin E. Disruption of the AhR-CDK2 interaction by TCDD would presumably prevent cyclin E binding and suppress CDK2 activity. Future studies will identify other proteins in the AhR-CDK2 complex, which may reveal novel mechanisms of TCDD toxicity.

Lauren Troy *, Cheri L. Lamb, Kristen A. Mitchell, Dept of Biological Science, Boise State University, Boise, ID 83725

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Author:Troy, Lauren; Lamb, Cheri L.; Mitchell, Kristen A.
Publication:Journal of the Idaho Academy of Science
Article Type:Report
Geographic Code:1USA
Date:Jun 1, 2010
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