β-Catenin as a multilayer modulator of zonal cytochrome P450 expression in mouse liver
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Albert Braeuning
Abstract
The liver is the major organ for metabolism of drugs and other xenobiotics. Expression of many drug-metabolizing enzymes is not equally distributed throughout the liver: under normal conditions, many of them, including the most relevant members of the cytochrome P450 superfamily, are exclusively expressed in a hepatocyte subpopulation located near branches of the efferent central vein. Activation of different ligand-dependent transcription factors by exogenous compounds stimulates high expression of certain cytochrome P450 isoforms. This process also occurs preferentially in perivenous hepatocytes. The mechanisms, however, which determine the zone-specificity of basal and xenobiotic-induced expression of cytochrome P450 enzymes, have remained largely unknown for decades. Very recently, signaling through the Wnt/β-catenin pathway has been implicated in the regulation of zonal gene expression in mouse liver. In this review, current knowledge of cytochrome P450 regulation by β-catenin-dependent transcription is summarized and underlying molecular mechanisms are discussed.
©2010 by Walter de Gruyter Berlin New York
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Articles in the same Issue
- EDITORIAL
- Highlight: Signal Transduction and Disease
- HIGHLIGHT: SIGNAL TRANSDUCTION AND DISEASE
- Phosphorylase and the origin of reversible protein phosphorylation
- β-Catenin as a multilayer modulator of zonal cytochrome P450 expression in mouse liver
- Glycome profiling using modern glycomics technology: technical aspects and applications
- Ubiquitin ligase complexes: from substrate selectivity to conjugational specificity
- MAP3K1 functionally interacts with Axin1 in the canonical Wnt signalling pathway
- Signal transduction by the atopy-associated human thymic stromal lymphopoietin (TSLP) receptor depends on Janus kinase function
- GENES AND NUCLEIC ACIDS
- 6S RNA-dependent inhibition of RNA polymerase is released by RNA-dependent synthesis of small de novo products
- PROTEIN STRUCTURE AND FUNCTION
- Analysis of the DNA-binding activity of p53 mutants using functional protein microarrays and its relationship to transcriptional activation
- Peptides from the Mycobacterium tuberculosis Rv1980c protein involved in human cell infection: insights into new synthetic subunit vaccine candidates
- The epimerase activity of anthocyanidin reductase from Vitis vinifera and its regiospecific hydride transfers
- Antibacterial activity of radical scavengers against class Ib ribonucleotide reductase from Bacillus anthracis
- CELL BIOLOGY AND SIGNALING
- Signal transduction in CHO cells stably transfected with domain-selective forms of murine ACE
- The impact of methylmercury on 1,25-dihydroxyvitamin D3-induced transcriptomic responses in dolphin skin cells
- PROTEOLYSIS
- An examination of the proteolytic activity for bovine pregnancy-associated glycoproteins 2 and 12
- Analysis of an autoproteolytic activity of rice yellow mottle virus silencing suppressor P1
- Identification of novel peptide inhibitors for human trypsins