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Aryl hydrocarbon receptor degradation-promoting factor (ADPF) and the control of the xenobiotic response.

Authors
Ma-Q
Source
Mol Interv 2007 Jun; 7(3):133-137
NIOSHTIC No.
20032539
Abstract
The study of xenobiotic metabolism has long been a core activity in pharmacology. The diverse chemical transformations of xenobiotics in vivo are elegant in themselves, depending as they do on a battery of enzymes that include the cytochomes P450 (CYPs), and their reaction mechanisms have been elucidated by a great many pioneering pharmacologists who helped to launch the discipline. Today, researchers are finding surprising and subtle intricacies in the molecular control that underpins the xenobiotic response. For example, the inducible expression of CYP-encoding genes above normal basal output is controlled by specialized xenobiotic activated receptors (XARs), which include the aryl hydrocarbon receptor (AhR). But because CYP activities can be double-edged, supporting a multiplicity of chemical transformations, their expression levels must be tightly regulated over time and biological space. Indeed, the kinetics of xenobiotic-induced CYP expression suggest multiple checks and balances at both transcriptional and post-translational levels. Recent research points to the regulated degradation of AhR as one aspect of control. A key participant in directing AhR degradation has been identified - the AhR degradation promoting factor (ADPF) - which appears to serve as an E3 ubiquitin ligase. The biological machinery that controls the xenobiotic response thus encompasses an elegance deep beneath the traditional recognition of CYPs as catalysts of xenobiotic degradation.
Keywords
Pharmacodynamics; Pharmacology; Metabolic-activation; Metabolic-rate; Metabolism; Metabolites; Enzyme-activity; Enzymes; Chemical-composition; Chemical-processing; Chemical-synthesis; Genetic-factors; Genes; Genetics; Biological-effects; Biological-factors; Biological-transport; Biological-function; Biological-systems
Contact
Qiang Ma, Receptor Biology Laboratory, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV 26505
CODEN
MIONAR
Publication Date
20070601
Document Type
Journal Article; Academic/Scholarly
Fiscal Year
2007
NTIS Accession No.
NTIS Price
Issue of Publication
3
ISSN
1534-0384
NIOSH Division
HELD
Source Name
Molecular Interventions
State
WV
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