Ligand-dependent recruitment of the Arnt coregulator determines DNA recognition by the dioxin receptor

Journal Article · Thu Apr 01 00:00:00 EST 1993 · Molecular and Cellular Biology; (United States)

DOI:https://doi.org/10.1128/MCB.13.4.2504· OSTI ID:6384277

Whitelaw, M; Pongratz, I; Wilhelmsson, A; Gustafsson, J; Poellinger, L ^[1]

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1. Huddinge University Hospital F-60 (Sweden)

Signal transduction by dioxins is mediated by the intracellular dioxin or aryl hydrocarbon receptor. This receptor binds dioxin and its planar aromatic congeners in a saturable manner with high affinity. The extreme toxicity of dioxin has been demonstrated in animals but not in humans. In animals, dioxin causes thymic wasting, immune suppression, severe epithelial disorders and tumor promotion. On a molecular level, dioxins are inducers of transcription of a battery of target genes encoding xenobiotic metabolizing enzymes. Dioxin also appears to transcriptionally regulate the expression of the growth modulatory genes for interleukin-1 Beta and plasminogen activator inhibitor-2. The dioxin induction response is mediated by single or multiple copies of dioxin-inducible transcriptional control elements in target promoters. The research data detailed in this paper examines the ligand-dependent recruitment of the Arnt coregulator which determines DNA recognition by the dioxin receptor. This data suggests that dioxin receptor activity is governed by a complex pattern of combinatorial regulation involving repression by hsp90 and then by ligand-dependent recruitment of the positive coregulator Arnt and that the dioxin receptor system provides the first example of signal-controlled dimerization of bHLH factors.

• OSTI ID: 6384277
• Journal Information: Molecular and Cellular Biology; (United States), Vol. 13:4; ISSN 0270-7306
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
59 BASIC BIOLOGICAL SCIENCES
DIOXIN
BIOLOGICAL EFFECTS
TOXICITY
DNA
CHEMICAL BONDS
RECEPTORS
BIOCHEMICAL REACTION KINETICS
DNA SEQUENCING
GENES
GENETIC ENGINEERING
PHYSIOLOGY
BIOTECHNOLOGY
HETEROCYCLIC COMPOUNDS
KINETICS
MEMBRANE PROTEINS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PROTEINS
REACTION KINETICS
STRUCTURAL CHEMICAL ANALYSIS
560300* - Chemicals Metabolism & Toxicology
550400 - Genetics