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

Biochemical Pharmacology

Volumn 96, Issue 4, 2015, Pages 357-368

  Wang, Yue Ming ^a   Chai, Sergio C ^a   Lin, Wenwei ^a   Chai, Xiaojuan ^b,c   Elias, Ayesha ^a   Wu, Jing ^a   Ong, Su Sien ^a   Pondugula, Satyanarayana R ^a,e   Beard, Jordan A ^a,d   Schuetz, Erin G ^a   Zeng, Su ^c   Xie, Wen ^b   Chen, Taosheng ^a,d  

^a ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

^b UNIVERSITY OF PITTSBURGH   (United States)

^c ZHEJIANG UNIVERSITY   (China)

^d UNIVERSITY OF TENNESSEE HEALTH SCIENCE CENTER   (United States)

^e AUBURN UNIVERSITY   (United States)

Author keywords

Gene regulation; Nuclear receptor; Receptor regulation; Transcription regulation; Xenobiotic

Indexed keywords

CYTOCHROME P450 3A4; PREGNANE X RECEPTOR; RETINOID X RECEPTOR ALPHA; SERINE; CYP3A11 PROTEIN, MOUSE; CYTOCHROME P450 3A; MEMBRANE PROTEIN; STEROID RECEPTOR;

ANIMAL EXPERIMENT; ARTICLE; CELLULAR DISTRIBUTION; COMPLEX FORMATION; CONTROLLED STUDY; DNA BINDING; GENE MUTATION; HUMAN; HUMAN CELL; IN VITRO STUDY; LIGAND BINDING; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN INTERACTION; PROTEIN PHOSPHORYLATION; TRANSACTIVATION; TRANSCRIPTION INITIATION; TRANSGENE; ANIMAL; CHEMICAL STRUCTURE; GENETICS; LIVER; METABOLISM; MUTATION; PHOSPHORYLATION; PROTEIN MULTIMERIZATION; TRANSGENIC MOUSE; TUMOR CELL LINE;

ANIMALS; CELL LINE, TUMOR; CYTOCHROME P-450 CYP3A; HUMANS; LIVER; MEMBRANE PROTEINS; MICE, TRANSGENIC; MODELS, MOLECULAR; MUTATION; PHOSPHORYLATION; PROTEIN MULTIMERIZATION; RECEPTORS, STEROID; RETINOID X RECEPTOR ALPHA; SERINE; TRANSCRIPTIONAL ACTIVATION;

EID: 84938293394     PISSN: 00062952     EISSN: 18732968     Source Type: Journal    
DOI: 10.1016/j.bcp.2015.06.018     Document Type: Article

References (48)

1. T.M. Willson, and S.A. Kliewer PXR, CAR and drug metabolism Nat. Rev. Drug Discov. 1 2002 259 266
2. Y.M. Wang, W. Lin, S.C. Chai, J. Wu, S.S. Ong, E.G. Schuetz, and T. Chen Piperine activates human pregnane X receptor to induce the expression of cytochrome P450 3A4 and multidrug resistance protein 1 Toxicol. Appl. Pharmacol. 272 2013 96 107
3. M. Sinz, S. Kim, Z. Zhu, T. Chen, M. Anthony, K. Dickinson, and A.D. Rodrigues Evaluation of 170 xenobiotics as transactivators of human pregnane X receptor (hPXR) and correlation to known CYP3A4 drug interactions Curr. Drug Metab. 7 2006 375 388
4. M.W. Sinz Evaluation of pregnane X receptor (PXR)-mediated CYP3A4 drug-drug interactions in drug development Drug Metab. Rev. 45 2013 3 14
5. T. Chen Nuclear receptor drug discovery Curr. Opin. Chem. Biol. 12 2008 418 426
6. R.M. Evans, and D.J.AT Nuclear Receptors, RXR and the Big Bang Mangelsdorf Cell 157 2014 255 266
7. P. Germain, B. Staels, C. Dacquet, M. Spedding, and V. Laudet Overview of nomenclature of nuclear receptors Pharmacol. Rev. 58 2006 685 704
8. W. Lin, J. Wu, H. Dong, D. Bouck, F.Y. Zeng, and T. Chen Cyclin-dependent kinase 2 negatively regulates human pregnane X receptor-mediated CYP3A4 gene expression in HepG2 liver carcinoma cells J. Biol. Chem. 283 2008 30650 30657
9. K. Lichti-Kaiser, D. Brobst, C. Xu, and J.L. Staudinger A systematic analysis of predicted phosphorylation sites within the human pregnane X receptor protein J. Pharmacol. Exp. Ther. 331 2009 65 76
10. S.R. Pondugula, C. Brimer-Cline, J. Wu, E.G. Schuetz, R.K. Tyagi, and T. Chen A phosphomimetic mutation at threonine-57 abolishes transactivation activity and alters nuclear localization pattern of human pregnane x receptor Drug Metab. Dispos. 37 2009 719 730
11. A. Elias, A.A. High, A. Mishra, S.S. Ong, J. Wu, J. Peng, and T. Chen Identification and characterization of phosphorylation sites within the pregnane X receptor protein Biochem. Pharmacol. 87 2014 360 370
12. A. Doricakova, A. Novotna, R. Vrzal, P. Pavek, and Z. Dvorak The role of residues T248, Y249 and T422 in the function of human pregnane X receptor Arch. Toxicol. 87 2013 291 301
13. B.D. Wallace, L. Betts, G. Talmage, R.M. Pollet, N.S. Holman, and M.R. Redinbo Structural and functional analysis of the human nuclear xenobiotic receptor PXR in complex with RXRalpha J. Mol. Biol. 425 2013 2561 2577
14. J.A. Ubersax, and J.E. Ferrell Jr. Mechanisms of specificity in protein phosphorylation Nat. Rev. Mol. Cell Biol. 8 2007 530 541
15. L. Sivertsson, I. Edebert, M.P. Palmertz, M. Ingelman-Sundberg, and E.P. Neve Induced CYP3A4 expression in confluent Huh7 hepatoma cells as a result of decreased cell proliferation and subsequent pregnane X receptor activation Mol. Pharmacol. 83 2013 659 670
16. J. Sugatani, T. Uchida, M. Kurosawa, M. Yamaguchi, Y. Yamazaki, A. Ikari, and M. Miwa Regulation of pregnane X receptor (PXR) function and UGT1A1 gene expression by posttranslational modification of PXR protein Drug Metab. Dispos. 40 2012 2031 2040
17. X. Ma, Y. Shah, C. Cheung, G.L. Guo, L. Feigenbaum, K.W. Krausz, J.R. Idle, and F.J. Gonzalez The PREgnane X receptor gene-humanized mouse: a model for investigating drug-drug interactions mediated by cytochromes P450 3A Drug Metab. Dispos. 35 2007 194 200
18. H. Zhou, W. Liu, Y. Su, Z. Wei, J. Liu, S.K. Kolluri, H. Wu, Y. Cao, J. Chen, Y. Wu, T. Yan, X. Cao, W. Gao, A. Molotkov, F. Jiang, W.G. Li, B. Lin, H.P. Zhang, J. Yu, S.P. Luo, J.Z. Zeng, G. Duester, P.Q. Huang, and X.K. Zhang NSAID sulindac and its analog bind RXRalpha and inhibit RXRalpha-dependent AKT signaling Cancer Cell 17 2010 560 573
19. W. Lin, and T. Chen A vinblastine fluorescent probe for pregnane X receptor in a time-resolved fluorescence resonance energy transfer assay Anal. Biochem. 443 2013 252 260
20. W. Xie, J.L. Barwick, M. Downes, B. Blumberg, C.M. Simon, M.C. Nelson, B.A. Neuschwander-Tetri, E.M. Brunt, P.S. Guzelian, and R.M. Evans Humanized xenobiotic response in mice expressing nuclear receptor SXR Nature 406 2000 435 439
21. H. Gong, S.V. Singh, S.P. Singh, Y. Mu, J.H. Lee, S.P. Saini, D. Toma, S. Ren, V.E. Kagan, B.W. Day, P. Zimniak, and W. Xie Orphan nuclear receptor pregnane X receptor sensitizes oxidative stress responses in transgenic mice and cancerous cells Mol. Endocrinol. 20 2006 279 290
22. J. Zhou, M. Liu, Y. Zhai, and W. Xie The antiapoptotic role of pregnane X receptor in human colon cancer cells Mol. Endocrinol. 22 2008 868 880
23. E.J. Poulton, L. Levy, J.W. Lampe, D.D. Shen, J. Tracy, M.C. Shuhart, K.E. Thummel, and D.L. Eaton Sulforaphane is not an effective antagonist of the human pregnane X-receptor in vivo Toxicol. Appl. Pharmacol. 266 2013 122 131
24. S. Mani, H. Huang, S. Sundarababu, W. Liu, G. Kalpana, A.B. Smith, and S.B. Horwitz Activation of the steroid and xenobiotic receptor (human pregnane X receptor) by nontaxane microtubule-stabilizing agents Clin. Cancer Res. 11 2005 6359 6369
25. S. Harmsen, A.S. Koster, J.H. Beijnen, J.H. Schellens, and I. Meijerman Comparison of two immortalized human cell lines to study nuclear receptor-mediated CYP3A4 induction Drug Metab. Dispos. 36 2008 1166 1171
26. A. Gupta, G.M. Mugundu, P.B. Desai, K.E. Thummel, and J.D. Unadkat Intestinal human colon adenocarcinoma cell line LS180 is an excellent model to study pregnane X receptor, but not constitutive androstane receptor, mediated CYP3A4 and multidrug resistance transporter 1 induction: studies with anti-human immunodeficiency virus protease inhibitors Drug Metab. Dispos. 36 2008 1172 1180
27. R.N. Helsley, Y. Sui, N. Ai, S.H. Park, W.J. Welsh, C. Zhou, and X. Pregnane receptor mediates dyslipidemia induced by the HIV protease inhibitor amprenavir in mice Mol. Pharmacol. 83 2013 1190 1199
28. J.L. Staudinger, and K. Lichti Cell signaling and nuclear receptors: new opportunities for molecular pharmaceuticals in liver disease Mol. Pharm. 5 2008 17 34
29. D.G. Teotico, M.L. Frazier, F. Ding, N.V. Dokholyan, B.R. Temple, and M.R. Redinbo Active nuclear receptors exhibit highly correlated AF-2 domain motions PLoS Comput. Biol. 4 2008 e1000111
30. Y.M. Wang, S.S. Ong, S.C. Chai, and T. Chen Role of CAR and PXR in xenobiotic sensing and metabolism Expert Opin. Drug Metab. Toxicol. 8 2012 803 817
31. C.L. Worth, R. Preissner, and T.L. Blundell SDM - a server for predicting effects of mutations on protein stability and malfunction Nucleic Acids Res. 39 2011 W215 W222
32. N.L. Sim, P. Kumar, J. Hu, S. Henikoff, G. Schneider, and P.C. Ng SIFT web server: predicting effects of amino acid substitutions on proteins Nucleic Acids Res. 40 2012 W452 W457
33. Y. Bromberg, B. Rost, and SNAP: predict effect of non-synonymous polymorphisms on function Nucleic Acids Res. 35 2007 3823 3835
34. M. Matic, S. Nakhel, A.M. Lehnert, P. Polly, S.J. Clarke, and G.R. Robertson A novel approach to investigate the subcellular distribution of nuclear receptors in vivo Nucl. Recept. Signal 7 2009 e004
35. E.J. Squires, T. Sueyoshi, and M. Negishi Cytoplasmic localization of pregnane X receptor and ligand-dependent nuclear translocation in mouse liver J. Biol. Chem. 279 2004 49307 49314
36. K. Kawana, T. Ikuta, Y. Kobayashi, O. Gotoh, K. Takeda, and K. Kawajiri Molecular mechanism of nuclear translocation of an orphan nuclear receptor SXR Mol. Pharmacol. 63 2003 524 531
37. T. Smutny, S. Mani, and P. Pavek Post-translational and post-transcriptional modifications of pregnane X receptor (PXR) in regulation of the cytochrome P450 superfamily Curr. Drug Metab. 14 2013 1059 1069
38. J.J. Raybon, D. Pray, D.G. Morgan, M. Zoeckler, M. Zheng, M. Sinz, and S. Kim Pharmacokinetic-pharmacodynamic modeling of rifampicin-mediated Cyp3a11 induction in steroid and xenobiotic X receptor humanized mice J. Pharmacol. Exp. Ther. 337 2011 75 82
39. M.H. Delmotte, A. Tahayato, P. Formstecher, and P. Lefebvre Serine 157, a retinoic acid receptor alpha residue phosphorylated by protein kinase C in vitro, is involved in RXR.RARalpha heterodimerization and transcriptional activity J. Biol. Chem. 274 1999 38225 38231
40. J.P. Gray, K.A. Burns, T.L. Leas, G.H. Perdew, and J.P. Vanden Heuvel Regulation of peroxisome proliferator-activated receptor alpha by protein kinase C Biochemistry 44 2005 10313 10321
41. C. Blanquart, R. Mansouri, R. Paumelle, J.C. Fruchart, B. Staels, and C. Glineur The protein kinase C signaling pathway regulates a molecular switch between transactivation and transrepression activity of the peroxisome proliferator-activated receptor alpha Mol. Endocrinol. 18 2004 1906 1918
42. M. Guha, and Cyclin-dependent kinase inhibitors move into Phase III Nat. Rev. Drug Discov. 11 2012 892 894
43. T. Chen Overcoming drug resistance by regulating nuclear receptors Adv. Drug Deliv. Rev. 62 2010 1257 1264
44. S. Mani, W. Dou, and M.R. Redinbo PXR antagonists and implication in drug metabolism Drug Metab. Rev. 45 2013 60 72
45. M. Venkatesh, H. Wang, J. Cayer, M. Leroux, D. Salvail, B. Das, J.E. Wrobel, and S. Mani In vivo and in vitro characterization of a first-in-class novel azole analog that targets pregnane X receptor activation Mol. Pharmacol. 80 2011 124 135
46. H. Li, M.R. Redinbo, M. Venkatesh, S. Ekins, A. Chaudhry, N. Bloch, A. Negassa, P. Mukherjee, G. Kalpana, and S. Mani Novel yeast-based strategy unveils antagonist binding regions on the nuclear xenobiotic receptor PXR J. Biol. Chem. 288 2013 13655 13668
47. H. Wang, M. Venkatesh, H. Li, R. Goetz, S. Mukherjee, A. Biswas, L. Zhu, A. Kaubisch, L. Wang, J. Pullman, K. Whitney, M. Kuro-o, A.I. Roig, J.W. Shay, M. Mohammadi, and S. Mani Pregnane X receptor activation induces FGF19-dependent tumor aggressiveness in humans and mice J. Clin. Invest. 121 2011 3220 3232
48. N. Ouyang, S. Ke, N. Eagleton, Y. Xie, G. Chen, B. Laffins, H. Yao, B. Zhou, Y. Tian, and X. Pregnane receptor suppresses proliferation and tumourigenicity of colon cancer cells Br. J. Cancer 102 2010 1753 1761