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Role of CAR and PXR in xenobiotic sensing and metabolism
This review summarizes recent advances in elucidating the roles of PXR and CAR in the xenobiotic detoxification system and highlights the progress in understanding the regulation of PXM and CAR activity at the post-translational levels, as well as the structural basis for theregulation of these two xenobiotics sensors. Expand
Heterologous Expression, Purification, and Characterization of Recombinant Rat Cysteine Dioxygenase*
The milder conditions used in the isolation of the recombinant CDO allowed a more controlled study of the properties and activity of CDO, clarifying conflicting findings in the literature. Expand
Piperine activates human pregnane X receptor to induce the expression of cytochrome P450 3A4 and multidrug resistance protein 1.
The dichotomous effects of PIP on induction of CYP3A4 and MDR1 expression observed here and inhibition of their activity reported elsewhere challenges the potential use of Pip as a bioavailability enhancer and suggests that caution should be taken in PIP consumption during drug treatment in patients, particularly those who favor daily pepper spice or rely on certain pepper remedies. Expand
FE(II) Is the Native Cofactor for Escherichia coli Methionine Aminopeptidase*
Fe(II) is the likely metal used by MetAP in E. coli and other bacterial cells and is confirmed by analysis of N-terminal processed and unprocessed recombinant glutathione S-transferase proteins. Expand
Probes of the Catalytic Site of Cysteine Dioxygenase*
Kinetic studies using cysteine structural analogs show that most are inhibitors and that a terminal functional group bearing a negative charge is required for binding, and cysteamine is shown to be a potent activator of the enzyme without being a substrate. Expand
SPA70 is a potent antagonist of human pregnane X receptor
Many drugs bind to and activate human pregnane X receptor (hPXR) to upregulate drug-metabolizing enzymes, resulting in decreased drug efficacy and increased resistance. This suggests that hPXRExpand
Small-molecule modulators of the constitutive androstane receptor
Continuous efforts are needed to discover novel CAR inhibitors, with extensive understanding of their inhibitory mechanism, species selectivity, and discriminating power against other xenobiotic sensors. Expand
Blocking an N-terminal acetylation–dependent protein interaction inhibits an E3 ligase
The development of chemical probes targeting the N-terminal acetylation-dependent interaction between an E2 conjugating enzyme and DCN1, a subunit of a multiprotein E3 ligase for the ubiquitin-like protein NEDD8, demonstrate that N- terminally acetyl-dependent protein interactions are druggable targets, and provide insights into targeting multip Protein E2–E3 ligases. Expand
Pregnane X receptor and drug-induced liver injury
This review focuses on the recent progress in understanding PXR-mediated DILI and highlights the efforts made to assess and manage PXr-mediatedDILI during drug development. Expand
Serine 350 of human pregnane X receptor is crucial for its heterodimerization with retinoid X receptor alpha and transactivation of target genes in vitro and in vivo.
The finding that phosphorylation regulates hPXR activity has implications for development of novel hPxR antagonists and for safety evaluation during drug development. Expand