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Regulation of TCDD-induced degradation of Ah receptor by cycloheximide.

Authors
Ma-Q; Baldwin-KT; Renzelli-AJ; Antonini-JM
Source
Organohalogen Compounds. Dioxin 2000: 20th International Symposium on Halogenated Environmental Organic Pollutants and Persistent Organic Pollutants (POPs), Monterey, California, USA, August 13-17, 2000. Volume 49: Toxicology; Non-Ah Receptor Mechanisms Underlying Immunotoxicity and Neurotoxicity of non-Coplanar-PCBs, PBDEs and Orthoquinones; Molecular Biology of the Ah Receptor and Ah Receptor-Dependent Signaling; Immunotoxicity of Dioxins and POPs; Endocrine Disruption; Ecotoxicology and POPs. Denison MS, ed., Davis, CA: University of California, Davis, 2000 Aug; 49:318-321
Link
NIOSHTIC No.
20020998
Abstract
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) represents the prototype for a class of structurally related halogenated aromatic hydrocarbons (HAHs), including polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls 1,2 . Animals exposed to TCDD exhibit a wide range of toxic and adaptive responses, including a wasting syndrome, tumor promotion in skin and liver, cleft palate, chloracne, immune and endocrine dysfunctions, and induction of drug metabolizing enzymes 1-6. The health effect of TCDD on human beings remains a matter of debate. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor with a basic helix-loop-helix PAS (bHLH/PAS) modular structure 2,3,7,8. Mouse genetic studies implicate AhR in most of the biological responses to TCDD, presumably by affecting the expression of target genes 9-11. Studies on the induction of CYP1A1 gene expression by TCDD provided major mechanistic understanding of the mechanism of action and regulation of AhR 2,3. In uninduced cells, AhR is localized in the cytoplasm, complexed with hsp90 12 and AIP, an immunophiltin-type chaperon protein 13-15. Binding with an agonist triggers the dissociation of AhR from the associated proteins and translocation into nucleus, where AhR dimerizes with Arnt, another bHLHPAS transcription factor 16. The AhR/Arnt dimer binds to a specific nucleotide sequence termed DRE (dioxin responsive element) in the enhancer region of the CYP1A1 gene 17; the transcription activation domains of AhR are essential for the subsequent transcriptional events, including alterations in chromatin structure, binding of general transcription factors to the promoter, and induction of transcription of the gene 2,3.
Keywords
Halogenated-hydrocarbons; Halogenated-compounds; Aromatic-hydrocarbons; Laboratory-animals; Animals; Animal-studies; Toxic-effects; Tumors; Skin-tumors; Liver-tumors; Immune-system-disorders; Endocrine-system-disorders
CODEN
ORCOEP
CAS No.
66-81-9; 1746-01-6
Publication Date
20000813
Document Type
Conference/Symposia Proceedings
Editors
Denison-MS
Fiscal Year
2000
NTIS Accession No.
NTIS Price
ISBN No.
9780970331540
NIOSH Division
HELD
Source Name
Organohalogen Compounds. Dioxin 2000: 20th International Symposium on Halogenated Environmental Organic Pollutants and Persistent Organic Pollutants (POPs), Monterey, California, USA, August 13-17, 2000. Volume 49: Toxicology; Non-Ah Receptor Mechanisms Underlying Immunotoxicity and Neurotoxicity of non-Coplanar-PCBs, PBDEs and Orthoquinones; Molecular Biology of the Ah Receptor and Ah Receptor-Dependent Signaling; Immunotoxicity of Dioxins and POPs; Endocrine Disruption; Ecotoxicology and POPs
State
WV; CA
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