The role of residues T248, Y249 and T422 in the function of human pregnane X receptor

Archives of Toxicology

Volumn 87, Issue 2, 2013, Pages 291-301

  Doricakova, Aneta ^a   Novotna, Aneta ^a   Vrzal, Radim ^a   Pavek, Petr ^b   Dvorak, Zdenek ^a  

^a PALACKÝ UNIVERSITY   (Czech Republic)

^b Charles University in Prague Faculty of Pharmacy   (Czech Republic)

Author keywords

Cytochrome P450; Drug metabolism; Phosphorylation; Pregnane X receptor

Indexed keywords

ASPARTIC ACID; CYTOCHROME P450 3A4; DEATH RECEPTOR 3; HETERODIMER; MUTANT PROTEIN; PHOSPHOTRANSFERASE; PREGNANE X RECEPTOR; RETINOID X RECEPTOR ALPHA; THREONINE; TYROSINE; VALINE;

ACTIVATION FUNCTION 2 DOMAIN; ARTICLE; CELL STRAIN HEPG2; COMPUTER MODEL; CONSENSUS; CONTROLLED STUDY; CYP3A4 GENE; DNA RESPONSIVE ELEMENT; GENE ACTIVATION; GENE EXPRESSION; HUMAN; HUMAN CELL; LIGAND BINDING; NUCLEOTIDE SEQUENCE; PREDICTION; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; REPORTER GENE; RESIDUE ANALYSIS; SITE DIRECTED MUTAGENESIS; TRANSACTIVATION;

BINDING SITES; COMPUTER SIMULATION; CYTOCHROME P-450 CYP3A; GENE DOSAGE; HELA CELLS; HEP G2 CELLS; HUMANS; LIGANDS; MUTAGENESIS, SITE-DIRECTED; PHOSPHORYLATION; PROMOTER REGIONS, GENETIC; PROTEIN STRUCTURE, TERTIARY; RECEPTORS, STEROID; TRANSCRIPTIONAL ACTIVATION; TRANSFECTION;

EID: 84873734479     PISSN: 03405761     EISSN: 14320738     Source Type: Journal    
DOI: 10.1007/s00204-012-0937-9     Document Type: Article

References (47)

1. Andrews NC, Faller DV (1991) A rapid micropreparation technique for extraction of DNA-binding proteins from limiting numbers of mammalian cells. Nucleic Acids Res 19(9):2499
2. Bertilsson G, Heidrich J, Svensson K et al (1998) Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction. Proc Natl Acad Sci USA 95(21):12208-12213
3. Coumoul X, Diry M, Barouki R (2002) PXR-dependent induction of human CYP3A4 gene expression by organochlorine pesticides. Biochem Pharmacol 64(10):1513-1519
4. Dai G, He L, Bu P, Wan YJ (2008) Pregnane X receptor is essential for normal progression of liver regeneration. Hepatology 47(4):1277-1287
5. Ding X, Staudinger JL (2005a) Induction of drug metabolism by forskolin: the role of the pregnane X receptor and the protein kinase a signal transduction pathway. J Pharmacol Exp Ther 312(2):849-856
6. Ding X, Staudinger JL (2005b) Repression of PXR-mediated induction of hepatic CYP3A gene expression by protein kinase C. Biochem Pharmacol 69(5):867-873
7. Dowless MS, Barbee JL, Borchert KM, Bocchinfuso WP, Houck KA (2005) Cyclic AMP-independent activation of CYP3A4 gene expression by forskolin. Eur J Pharmacol 512(1):9-13. doi: 10.1016/j.ejphar.2005.02.022
8. Drocourt L, Pascussi JM, Assenat E, Fabre JM, Maurel P, Vilarem MJ (2001) Calcium channel modulators of the dihydropyridine family are human pregnane X receptor activators and inducers of CYP3A, CYP2B, and CYP2C in human hepatocytes. Drug Metab Dispos Biol Fate Chem 29(10):1325-1331
9. Frank C, Makkonen H, Dunlop TW, Matilainen M, Vaisanen S, Carlberg C (2005) Identification of pregnane X receptor binding sites in the regulatory regions of genes involved in bile acid homeostasis. J Mol Biol 346(2):505-519
10. Goodwin B, Hodgson E, Liddle C (1999) The orphan human pregnane X receptor mediates the transcriptional activation of CYP3A4 by rifampicin through a distal enhancer module. Mol Pharmacol 56(6):1329-1339
11. Goodwin B, Gauthier KC, Umetani M et al (2003) Identification of bile acid precursors as endogenous ligands for the nuclear xenobiotic pregnane X receptor. Proc Natl Acad Sci USA 100(1):223-228
12. Graves JD, Krebs EG (1999) Protein phosphorylation and signal transduction. Pharmacol Ther 82(2-3):111-121
13. Harmsen S, Meijerman I, Beijnen JH, Schellens JH (2007) The role of nuclear receptors in pharmacokinetic drug-drug interactions in oncology. Cancer Treat Rev 33(4):369-380
14. Henklova P, Vrzal R, Papouskova B et al (2008) SB203580, a pharmacological inhibitor of p38 MAP kinase transduction pathway activates ERK and JNK MAP kinases in primary cultures of human hepatocytes. Eur J Pharmacol 593(1-3):16-23
15. Hunter T, Karin M (1992) The regulation of transcription by phosphorylation. Cell 70(3):375-387
16. Igarashi M, Yogiashi Y, Mihara M, Takada I, Kitagawa H, Kato S (2007) Vitamin K induces osteoblast differentiation through pregnane X receptor-mediated transcriptional control of the Msx2 gene. Mol Cell Biol 27(22):7947-7954
17. Jones SA, Moore LB, Shenk JL et al (2000) The pregnane X receptor: a promiscuous xenobiotic receptor that has diverged during evolution. Mol Endocrinol 14(1):27-39
18. Karin M (1994) Signal transduction from the cell surface to the nucleus through the phosphorylation of transcription factors. Curr Opin Cell Biol 6(3):415-424
19. Klaassen CD, Slitt AL (2005) Regulation of hepatic transporters by xenobiotic receptors. Curr Drug Metab 6(4):309-328
20. Kliewer SA, Moore JT, Wade L et al (1998) An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell 92(1):73-82
21. Lee JH, Zhou J, Xie W (2008) PXR and LXR in hepatic steatosis: a new dog and an old dog with new tricks. Mol Pharm 5(1):60-66
22. Lehmann JM, McKee DD, Watson MA, Willson TM, Moore JT, Kliewer SA (1998) The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. J Clin Invest 102(5):1016-1023
23. Lichti-Kaiser K, Brobst D, Xu C, Staudinger JL (2009a) A systematic analysis of predicted phosphorylation sites within the human pregnane X receptor protein. J Pharmacol Exp Ther 331(1):65-76
24. Lichti-Kaiser K, Xu C, Staudinger JL (2009b) Cyclic AMP-dependent protein kinase signaling modulates pregnane x receptor activity in a species-specific manner. J Biol Chem 284(11):6639-6649
25. Lin W, Wu J, Dong H, Bouck D, Zeng FY, Chen T (2008) Cyclin-dependent kinase 2 negatively regulates human pregnane X receptor-mediated CYP3A4 gene expression in HepG2 liver carcinoma cells. J Biol Chem 283(45):30650-30657
26. Moore LB, Maglich JM, McKee DD et al (2002) Pregnane X receptor (PXR), constitutive androstane receptor (CAR), and benzoate X receptor (BXR) define three pharmacologically distinct classes of nuclear receptors. Mol Endocrinol 16(5):977-986
27. Moreau A, Vilarem MJ, Maurel P, Pascussi JM (2008) Xenoreceptors CAR and PXR activation and consequences on lipid metabolism, glucose homeostasis, and inflammatory response. Mol Pharm 5(1):35-41
28. Ngan CH, Beglov D, Rudnitskaya AN, Kozakov D, Waxman DJ, Vajda S (2009) The structural basis of pregnane X receptor binding promiscuity. Biochemistry 48(48):11572-11581
29. Pacyniak EK, Cheng X, Cunningham ML, Crofton K, Klaassen CD, Guo GL (2007) The flame retardants, polybrominated diphenyl ethers, are pregnane X receptor activators. Toxicol Sci 97(1):94-102
30. Pascussi JM, Gerbal-Chaloin S, Duret C, Daujat-Chavanieu M, Vilarem MJ, Maurel P (2008) The tangle of nuclear receptors that controls xenobiotic metabolism and transport: crosstalk and consequences. Annu Rev Pharmacol Toxicol 48:1-32
31. Pavek P, Cerveny L, Svecova L et al (2007) Examination of Glucocorticoid receptor alpha-mediated transcriptional regulation of P-glycoprotein, CYP3A4, and CYP2C9 genes in placental trophoblast cell lines. Placenta 28(10):1004-1011
32. Pondugula SR, Brimer-Cline C, Wu J, Schuetz EG, Tyagi RK, Chen T (2009) A phosphomimetic mutation at threonine-57 abolishes transactivation activity and alters nuclear localization pattern of human pregnane x receptor. Drug Metab Dispos 37(4):719-730
33. Roth A, Looser R, Kaufmann M et al (2008) Regulatory cross-talk between drug metabolism and lipid homeostasis: constitutive androstane receptor and pregnane X receptor increase Insig-1 expression. Mol Pharmacol 73(4):1282-1289
34. Ruhl R (2005) Induction of PXR-mediated metabolism by beta-carotene. Biochim Biophys Acta 1740(2):162-169
35. Rushmore TH, Kong AN (2002) Pharmacogenomics, regulation and signaling pathways of phase I and II drug metabolizing enzymes. Curr Drug Metab 3(5):481-490
36. Staudinger J, Liu Y, Madan A, Habeebu S, Klaassen CD (2001) Coordinate regulation of xenobiotic and bile acid homeostasis by pregnane X receptor. Drug Metab Dispos 29(11):1467-1472
37. Staudinger JL, Ding X, Lichti K (2006) Pregnane X receptor and natural products: beyond drug-drug interactions. Expert Opin Drug Metab Toxicol 2(6):847-857
38. Traber MG (2004) Vitamin E, nuclear receptors and xenobiotic metabolism. Arch Biochem Biophys 423(1):6-11
39. Ueda A, Matsui K, Yamamoto Y, Pedersen LC, Sueyoshi T, Negishi M (2005) Thr176 regulates the activity of the mouse nuclear receptor CAR and is conserved in the NR1I subfamily members PXR and VDR. Biochem J 388(Pt 2):623-630
40. Wada T, Gao J, Xie W (2009) PXR and CAR in energy metabolism. Trends Endocrinol Metab 20(6):273-279
41. Wang H, Huang H, Li H et al (2007) Activated pregnenolone X-receptor is a target for ketoconazole and its analogs. Clin Cancer Res 13(8):2488-2495
42. Watkins RE, Wisely GB, Moore LB et al (2001) The human nuclear xenobiotic receptor PXR: structural determinants of directed promiscuity. Science 292(5525):2329-2333
43. Waxman DJ (1999) P450 gene induction by structurally diverse xenochemicals: central role of nuclear receptors CAR, PXR, and PPAR. Arch Biochem Biophys 369(1):11-23
44. Xie W, Radominska-Pandya A, Shi Y et al (2001) An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids. Proc Natl Acad Sci USA 98(6):3375-3380
45. Zhang B, Xie W, Krasowski MD (2008) PXR: a xenobiotic receptor of diverse function implicated in pharmacogenetics. Pharmacogenomics 9(11):1695-1709
46. Zhou J, Zhai Y, Mu Y et al (2006) A novel pregnane X receptor-mediated and sterol regulatory element-binding protein-independent lipogenic pathway. J Biol Chem 281(21):15013-15020
47. Zhou J, Febbraio M, Wada T et al (2008) Hepatic fatty acid transporter Cd36 is a common target of LXR, PXR, and PPARgamma in promoting steatosis. Gastroenterology 134(2):556-567