Maximal aryl hydrocarbon receptor activity depends on an interaction with the retinoblastoma protein.
The aryl hydrocarbon receptor (AhR) belongs to the basic helix-loop-helix/periodicity/AhR nuclear translocator/simple-minded (Per-Arnt-Sim) family of transcription factors that regulate critical functions during development and tissue homeostasis. Within this family, the AhR is the only member conditionally activated in response to ligand binding, typified by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We recently demonstrated that the AhR interacts with the retinoblastoma protein (pRb). This report presents evidence that a LXCXE motif in the AhR protein confers pRb binding, which is necessary for maximal TCDD induced G(1) arrest in rat 5L hepatoma cells. The data support a mechanism whereby pRb seems to regulate G(1) cell cycle progression distinct from the direct repression of E2F-mediated transcription. Furthermore, the results indicate that the AhR-pRb interaction regulates TCDD induction of CYP1A1, suggesting that pRb may be a general AhR coactivator.
Institute of Chemical Toxicology, Wayne State University, Detroit, Michigan 48201, USA. cornelis_elferink@wayne.edu
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D020816:Amino Acid Motifs / Q000502:physiology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D016297:Mutagenesis, Site-Directed; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D011233:Precipitin Tests; D011485:Protein Binding / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000235:genetics; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured; D020798:Two-Hybrid System Techniques
D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D016160:Retinoblastoma Protein; D019363:Cytochrome P-450 CYP1A1