An introduction to the molecular basics of aryl hydrocarbon receptor biology

Biological Chemistry

Volumn 391, Issue 11, 2010, Pages 1235-1248

  Abel, Josef ^a   Haarmann Stemmann, Thomas ^a  

^a HEINRICH HEINE UNIVERSITY   (Germany)

Author keywords

aryl hydrocarbon receptor; cytochrome P450; dioxin; transcription factor; xenobiotic metabolism

Indexed keywords

2,3,7,8 TETRACHLORODIBENZO PARA DIOXIN; 2,3,7,8 TETRACHLORODIBENZOFURAN; 3 METHYLCHOLANTHRENE; 3,3',4,4',5 PENTACHLOROBIPHENYL; AROMATIC HYDROCARBON RECEPTOR; BENZO[A]PYRENE; BERBERINE; CURCUMIN; DICLOFENAC; DIMETHYLBENZ[A]ANTHRACENE; ENVIRONMENTAL CHEMICAL; INDOLE DERIVATIVE; LIGAND; NATURAL ORGANIC MATTER; OMEPRAZOLE; QUERCETIN; RESVERATROL; RUTAECARPINE; STEROID HORMONE RECEPTOR BLOCKING AGENT; SULINDAC; TATA BINDING PROTEIN; TRANSCRIPTION FACTOR II;

CELL DIFFERENTIATION; GENE CONTROL; GENE STRUCTURE; GENETIC TRANSCRIPTION; HUMAN; LIGAND BINDING; MOLECULAR BIOLOGY; NONHUMAN; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; T LYMPHOCYTE; TRANSCRIPTION TERMINATION; UBIQUITINATION; ULTRAVIOLET B RADIATION;

ALKALOIDS; ANIMALS; ARYL HYDROCARBON HYDROXYLASES; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; CAENORHABDITIS ELEGANS; CELL DIFFERENTIATION; CYTOCHROME P-450 ENZYME SYSTEM; DIOXINS; DROSOPHILA MELANOGASTER; ENVIRONMENTAL POLLUTANTS; FLAVONOIDS; GENE EXPRESSION REGULATION; HUMANS; HYDROCARBONS, AROMATIC; HYDROCARBONS, HALOGENATED; INDOLES; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; MICE; RATS; RECEPTORS, ARYL HYDROCARBON; SIGNAL TRANSDUCTION; STRUCTURE-ACTIVITY RELATIONSHIP; TRANSCRIPTION FACTORS; UBIQUITINATION; ULTRAVIOLET RAYS; XENOBIOTICS;

EID: 78649339242     PISSN: 14316730     EISSN: 14374315     Source Type: Journal    
DOI: 10.1515/BC.2010.128     Document Type: Review

References (150)

1. Abbott, B.D., Birnbaum, L.S., and Perdew, G.H. (1995). Developmental expression of two members of a new class of transcription factors: I. Expression of aryl hydrocarbon receptor in the C57BL/6N mouse embryo. Dev. Dyn. 204, 133-143.
2. Abbott, B.D., Schmid, J.E., Pitt, J.A., Buckalew, A.R., Wood, C.R., Held, G.A., and Diliberto, J.J. (1999). Adverse reproductive outcomes in the transgenic Ah receptor-deficient mouse. Toxicol. Appl. Pharmacol. 155, 62-70.
3. Adachi, J., Mori, Y., Matsui, S., Takigami, H., Fujino, J., Kitagawa, H., Miller, C.A. III, Kato, T., Saeki, K., and Matsuda, T. (2001). Indirubin and indigo are potent aryl hydrocarbon receptor ligands present in human urine. J. Biol. Chem. 276, 31475-31478.
4. Arpiainen, S., Raffalli-Mathieu, F., Lang, M.A., Pelkonen, O., and Hakkola, J. (2005). Regulation of the Cyp2a5 gene involves an aryl hydrocarbon receptor-dependent pathway. Mol. Pharmacol. 67, 1325-1333.
5. Baba, T., Mimura, J., Nakamura, N., Harada, N., Yamamoto, M., Morohashi, K.I., and Fujii-Kuriyama, Y. (2005). Intrinsic function of the aryl hydrocarbon (dioxin) receptor as a key factor in female reproduction. Mol. Cell. Biol. 25, 10040-10051.
6. Bass, S.E., Sienkiewicz, P., MacDonald, C.J., Cheng, R.Y., Spara-tore, A., Del Soldato, P., Roberts, D.D., Moody, T.W., Wink, D.A., and Yeh, G.C. (2009). Novel dithiolethione-modified nonsteroidal anti-inflammatory drugs in human hepatoma HepG2 and colon LS180 cells. Clin. Cancer Res. 15, 1964-1972.
7. Beischlag, T.V., Wang, S., Rose, D.W., Torchia, J., Reisz-Porszasz, S., Muhammad, K., Nelson, W.E., Probst, M.R., Rosenfeld, M.G., and Hankinson, O. (2002). Recruitment of the NCoA/SRC-1/p160 family of transcriptional coactivators by the aryl hydrocarbon receptor/aryl hydrocarbon receptor nuclear trans-locator complex. Mol. Cell. Biol. 22, 4319-4333.
8. Bell, D.R. and Poland, A. (2000). Binding of aryl hydrocarbon receptor (AhR) to AhR-interacting protein. The role of hsp90. J. Biol. Chem. 275, 36407-36414.
9. Bernshausen, T., Jux, B., Esser, C., Abel, J., and Fritsche, E. (2006). Tissue distribution and function of the aryl hydrocarbon receptor repressor (AhRR) in C57BL/6 and aryl hydrocarbon receptor deficient mice. Arch. Toxicol. 80, 206-211.
10. Bock, K.W. and Köhle, C. (2006). Ah receptor: dioxin-mediated toxic responses as hints to deregulated physiologic functions. Biochem. Pharmacol. 72, 393-404.
11. Bothe, H., Gotz, C., Stobbe-Maicherski, N., Fritsche, E., Abel, J., and Haarmann-Stemmann, T. (2010). Luteolin enhances the bio-availability of benzowaxpyrene in human colon carcinoma cells. Arch. Biochem. Biophys. 498, 111-118.
12. Burbach, K.M., Poland, A., and Bradfield, C.A. (1992). Cloning of the Ah-receptor cDNA reveals a distinctive ligand-activated transcription factor. Proc. Natl. Acad. Sci. USA 89, 8185-8189.
13. Chan, W.K., Yao, G., Gu, Y.Z., and Bradfield, C.A. (1999). Crosstalk between the aryl hydrocarbon receptor and hypoxia induc-ible factor signaling pathways. Demonstration of competition and compensation. J. Biol. Chem. 274, 12115-12123.
14. Chen, Y.H. and Tukey, R.H. (1996). Protein kinase C modulates regulation of the CYP1A1 gene by the aryl hydrocarbon receptor. J. Biol. Chem. 271, 26261-26266.
15. Chesire, D.R., Dunn, T.A., Ewing, C.M., Luo, J., and Isaacs, W.B. (2004). Identification of aryl hydrocarbon receptor as a putative Wnt/b-catenin pathway target gene in prostate cancer cells. Cancer Res. 64, 2523-2533.
16. Ciolino, H.P. and Yeh, G.C. (1999). Inhibition of aryl hydrocarbon-induced cytochrome P-450 1A1 enzyme activity and CYP1A1 expression by resveratrol. Mol. Pharmacol. 56, 760-767.
17. Ciolino, H.P., Daschner, P.J., Wang, T.T., and Yeh, G.C. (1998a). Effect of curcumin on the aryl hydrocarbon receptor and cyto-chrome P450 1A1 in MCF-7 human breast carcinoma cells. Bio-chem. Pharmacol. 56, 197-206.
18. Ciolino, H.P., Wang, T.T., and Yeh, G.C. (1998b). Diosmin and dios-metin are agonists of the aryl hydrocarbon receptor that differentially affect cytochrome P450 1A1 activity. Cancer Res. 58, 2754-2760.
19. Ciolino, H.P., Daschner, P.J., and Yeh, G.C. (1999). Dietary flavo-nols quercetin and kaempferol are ligands of the aryl hydrocarbon receptor that affect CYP1A1 transcription differentially. Biochem. J. 340, 715-722.
20. Ciolino, H.P., MacDonald, C.J., Memon, O.S., Bass, S.E., and Yeh, G.C. (2006). Sulindac regulates the aryl hydrocarbon receptor-mediated expression of phase 1 metabolic enzymes in vivo and in vitro. Carcinogenesis 27, 1586-1592.
21. Citri, Y., Colot, H.V., Jacquier, A.C., Yu, Q., Hall, J.C., Baltimore, D., and Rosbash, M. (1987). A family of unusually spliced biologically active transcripts encoded by a Drosophila clock gene. Nature 326, 42-47.
22. Coumailleau, P., Poellinger, L., Gustafsson, J.A., and Whitelaw, M.L. (1995). Definition of a minimal domain of the dioxin receptor that is associated with Hsp90 and maintains wild type ligand binding affinity and specificity. J. Biol. Chem. 270, 25291-25300.
23. Davarinos, N.A. and Pollenz, R.S. (1999). Aryl hydrocarbon receptor imported into the nucleus following ligand binding is rapidly degraded via the cytoplasmic proteasome following nuclear export. J. Biol. Chem. 274, 28708-28715.
24. Delescluse, C., Ledirac, N., Li, R., Piechocki, M.P., Hines, R.N., Gidrol, X., and Rahmani, R. (2001). Induction of cytochrome P450 1A1 gene expression, oxidative stress, and genotoxicity by carbaryl and thiabendazole in transfected human HepG2 and lymphoblastoid cells. Biochem. Pharmacol. 61, 399-407.
25. r 90,000 heat shock protein: a structural kinship with the gluco-corticoid receptor. Biochem. Biophys. Res. Commun. 155, 801-807.
26. Denison, M.S. and Nagy, S.R. (2003). Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals. Annu. Rev. Pharmacol. Toxicol. 43, 309-334.
27. Denison, M.S., Pandini, A., Nagy, S.R., Baldwin, E.P., and Bonati, L. (2002). Ligand binding and activation of the Ah receptor. Chem. Biol. Interact. 141, 3-24.
28. DeVito, M.J., Thomas, T., Martin, E., Umbreit, T.H., and Gallo, M.A. (1992). Antiestrogenic action of 2,3,7,8-tetrachlorodiben-zo-p-dioxin: tissue-specific regulation of estrogen receptor in CD1 mice. Toxicol. Appl. Pharmacol. 113, 284-292.
29. Döhr, O. and Abel, J. (1997). Transforming growth factor b1 core-gulates mRNA expression of aryl hydrocarbon receptor and cell-cycle-regulating genes in human cancer cell lines. Biochem. Biophys. Res. Commun. 241, 86-91.
30. Döhr, O., Li, W., Donat, S., Vogel, C., and Abel, J. (1996). Aryl hydrocarbon receptor mRNA levels in different tissues of 2,3,7,8- tetrachlorodibenzo-p-dioxin-responsive and nonrespon-sive mice. Adv. Exp. Med. Biol. 387, 447-459.
31. Döhr, O., Sinning, R., Vogel, C., Münzel, P., and Abel, J. (1997). Effect of transforming growth factor b1 on expression of aryl hydrocarbon receptor and genes of Ah gene battery: clues for independent down-regulation in A549 cells. Mol. Pharmacol. 51, 703-710.
32. Dolwick, K.M., Schmidt, J.V., Carver, L.A., Swanson, H.I., and Bradfield, C.A. (1993). Cloning and expression of a human Ah receptor cDNA. Mol. Pharmacol. 44, 911-917.
33. Duncan, D.M., Burgess, E.A., and Duncan, I. (1998). Control of distal antennal identity and tarsal development in Drosophila by spineless-aristapedia, a homolog of the mammalian dioxin receptor. Genes Dev. 12, 1290-1303.
34. Eguchi, H., Hayashi, S., Watanabe, J., Gotoh, O., and Kawajiri, K. (1994). Molecular cloning of the human AH receptor gene promoter. Biochem. Biophys. Res. Commun. 203, 615-622.
35. Ema, M., Matsushita, N., Sogawa, K., Ariyama, T., Inazawa, J., Nemoto, T., Ota, M., Oshimura, M., and Fujii-Kuriyama, Y. (1994). Human arylhydrocarbon receptor: functional expression and chromosomal assignment to 7p21. J. Biochem. 116, 845-851.
36. Enan, E. and Matsumura, F. (1996). Identification of c-Src as the integral component of the cytosolic Ah receptor complex, transducing the signal of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) through the protein phosphorylation pathway. Biochem. Pharmacol. 52, 1599-1612.
37. Esser, C. (2009). The immune phenotype of AhR null mouse mutants: not a simple mirror of xenobiotic receptor over-activation. Biochem. Pharmacol. 77, 597-607.
38. Fallone, F., Villard, P.H., Decome, L., Seree, E., Meo, M., Chacon, C., Durand, A., Barra, Y., and Lacarelle, B. (2005). PPARa activation potentiates AhR-induced CYP1A1 expression. Toxicology 216, 122-128.
39. Fernandez-Salguero, P., Pineau, T., Hilbert, D.M., McPhail, T., Lee, S.S., Kimura, S., Nebert, D.W., Rudikoff, S., Ward, J.M., and Gonzalez, F.J. (1995). Immune system impairment and hepatic fibrosis in mice lacking the dioxin-binding Ah receptor. Science 268, 722-726.
40. Fernandez-Salguero, P.M., Hilbert, D.M., Rudikoff, S., Ward, J.M., and Gonzalez, F.J. (1996). Aryl-hydrocarbon receptor-deficient mice are resistant to 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced toxicity. Toxicol. Appl. Pharmacol. 140, 173-179.
41. FitzGerald, C.T., Nebert, D.W., and Puga, A. (1998). Regulation of mouse Ah receptor (Ahr) gene basal expression by members of the Sp family of transcription factors. DNA Cell Biol. 17, 811-822.
42. Fritsche, E., Schafer, C., Calles, C., Bernsmann, T., Bernshausen, T., Wurm, M., Hubenthal, U., Cline, J.E., Hajimiragha, H., Schroeder, P., et al. (2007). Lightening up the UV response by identification of the arylhydrocarbon receptor as a cytoplasmatic target for ultraviolet B radiation. Proc. Natl. Acad. Sci. USA 104, 8851-8856.
43. Fukunaga, B.N., Probst, M.R., Reisz-Porszasz, S., and Hankinson, O. (1995). Identification of functional domains of the aryl hydrocarbon receptor. J. Biol. Chem. 270, 29270-29278.
44. Garrison, P.M. and Denison, M.S. (2000). Analysis of the murine AhR gene promoter. J. Biochem. Mol. Toxicol. 14, 1-10.
45. Garrison, P.M., Rogers, J.M., Brackney, W.R., and Denison, M.S. (2000). Effects of histone deacetylase inhibitors on the Ah receptor gene promoter. Arch. Biochem. Biophys. 374, 161-171.
46. Ge, N.L. and Elferink, C.J. (1998). A direct interaction between the aryl hydrocarbon receptor and retinoblastoma protein. Linking dioxin signaling to the cell cycle. J. Biol. Chem. 273, 22708-22713.
47. Gillner, M., Bergman, J., Cambillau, C., Alexandersson, M., Ferns-trom, B., and Gustafsson, J.A. (1993). Interactions of indolow3,2-bxcarbazoles and related polycyclic aromatic hydrocarbons with specific binding sites for 2,3,7,8-tetrachlorodibenzo-p-dioxin in rat liver. Mol. Pharmacol. 44, 336-345.
48. Gouedard, C., Barouki, R., and Morel, Y. (2004). Dietary polyphe-nols increase paraoxonase 1 gene expression by an aryl hydrocarbon receptor-dependent mechanism. Mol. Cell. Biol. 24, 5209-5222.
49. Gu, Y.Z., Hogenesch, J.B., and Bradfield, C.A. (2000). The PAS superfamily: sensors of environmental and developmental signals. Annu. Rev. Pharmacol. Toxicol. 40, 519-561.
50. Haarmann-Stemmann, T., Bothe, H., Kohli, A., Sydlik, U., Abel, J., and Fritsche, E. (2007). Analysis of the transcriptional regulation and molecular function of the aryl hydrocarbon receptor repres-sor in human cell lines. Drug Metab. Dispos. 35, 2262-2269.
51. Haarmann-Stemmann, T., Bothe, H., and Abel, J. (2009). Growth factors, cytokines and their receptors as downstream targets of arylhydrocarbon receptor (AhR) signaling pathways. Biochem. Pharmacol. 77, 508-520.
52. Haarmann-Stemmann, T., Sendker, J., Gotz, C., Krug, N., Bothe, H., Fritsche, E., Proksch, P., and Abel, J. (2010). Regulation of dioxin receptor function by different b-carboline alkaloids. Arch. Toxicol. 84, 619-629.
53. Hahn, M.E. (2002). Aryl hydrocarbon receptors: diversity and evolution. Chem. Biol. Interact. 141, 131-160.
54. Hankinson, O. (2005). Role of coactivators in transcriptional activation by the aryl hydrocarbon receptor. Arch. Biochem. Bio-phys. 433, 379-386.
55. Hestermann, E.V. and Brown, M. (2003). Agonist and chemopre-ventative ligands induce differential transcriptional cofactor recruitment by aryl hydrocarbon receptor. Mol. Cell. Biol. 23, 7920-7925.
56. Hosoya, T., Harada, N., Mimura, J., Motohashi, H., Takahashi, S., Nakajima, O., Morita, M., Kawauchi, S., Yamamoto, M., and Fujii-Kuriyama, Y. (2008). Inducibility of cytochrome P450 1A1 and chemical carcinogenesis by benzowaxpyrene in AhR repres-sor-deficient mice. Biochem. Biophys. Res. Commun. 365, 562-567.
57. Ikuta, T. and Kawajiri, K. (2006). Zinc finger transcription factor Slug is a novel target gene of aryl hydrocarbon receptor. Exp. Cell Res. 312, 3585-3594.
58. Ikuta, T., Eguchi, H., Tachibana, T., Yoneda, Y., and Kawajiri, K. (1998). Nuclear localization and export signals of the human aryl hydrocarbon receptor. J. Biol. Chem. 273, 2895-2904.
59. Ikuta, T., Kobayashi, Y., and Kawajiri, K. (2004a). Cell density regulates intracellular localization of aryl hydrocarbon receptor. J. Biol. Chem. 279, 19209-19216.
60. Ikuta, T., Kobayashi, Y., and Kawajiri, K. (2004b). Phosphorylation of nuclear localization signal inhibits the ligand-dependent nuclear import of aryl hydrocarbon receptor. Biochem. Biophys. Res. Commun. 317, 545-550.
61. Jain, S., Maltepe, E., Lu, M.M., Simon, C., and Bradfield, C.A. (1998). Expression of ARNT, ARNT2, HIF1a, HIF2a and Ah receptor mRNAs in the developing mouse. Mech. Dev. 73, 117-123.
62. Jaiswal, A.K. (1991). Human NAD(P)H:quinone oxidoreductase (NQO1) gene structure and induction by dioxin. Biochemistry 30, 10647-10653.
63. Jana, N.R., Sarkar, S., Ishizuka, M., Yonemoto, J., Tohyama, C., and Sone, H. (1999). Cross-talk between 2,3,7,8-tetrachlorodibenzo-p-dioxin and testosterone signal transduction pathways in LNCaP prostate cancer cells. Biochem. Biophys. Res. Commun. 256, 462-468.
64. Karchner, S.I., Jenny, M.J., Tarrant, A.M., Evans, B.R., Kang, H.J., Bae, I., Sherr, D.H., and Hahn, M.E. (2009). The active form of human aryl hydrocarbon receptor (AHR) repressor lacks exon 8, and its Pro 185 and Ala 185 variants repress both AHR and hypoxia-inducible factor. Mol. Cell. Biol. 29, 3465-3477.
65. Katiyar, S.K., Matsui, M.S., and Mukhtar, H. (2000). Ultraviolet-B exposure of human skin induces cytochromes P450 1A1 and 1B1. J. Invest. Dermatol. 114, 328-333.
66. Min/qmice with natural ligands. Proc. Natl. Acad. Sci. USA 106, 13481-13486.
67. Kazlauskas, A., Poellinger, L., and Pongratz, I. (1999). Evidence that the co-chaperone p23 regulates ligand responsiveness of the dioxin (aryl hydrocarbon) receptor. J. Biol. Chem. 274, 13519-13524.
68. Kazlauskas, A., Poellinger, L., and Pongratz, I. (2000). The immu-nophilin-like protein XAP2 regulates ubiquitination and subcel-lular localization of the dioxin receptor. J. Biol. Chem. 275, 41317-41324.
69. Kerkvliet, N.I. (2002). Recent advances in understanding the mechanisms of TCDD immunotoxicity. Int. Immunopharmacol. 2, 277-291.
70. Kerkvliet, N.I. (2009). AHR-mediated immunomodulation: the role of altered gene transcription. Biochem. Pharmacol. 77, 746-760.
71. Ko, H.P., Okino, S.T., Ma, Q., and Whitlock, J.P. Jr. (1997). Trans-activation domains facilitate promoter occupancy for the dioxin-inducible CYP1A1 gene in vivo. Mol. Cell Biol. 17, 3497-3507.
72. Kobayashi, A., Numayama-Tsuruta, K., Sogawa, K., and Fujii-Kuriyama, Y. (1997). CBP/p300 functions as a possible tran-scriptional coactivator of Ah receptor nuclear translocator (Arnt). J. Biochem. 122, 703-710.
73. Köhle, C. and Bock, K.W. (2007). Coordinate regulation of phase I and II xenobiotic metabolisms by the Ah receptor and Nrf2. Biochem. Pharmacol. 73, 1853-1862.
74. Köhle, C., Gschaidmeier, H., Lauth, D., Topell, S., Zitzer, H., and Bock, K.W. (1999). 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-mediated membrane translocation of c-Src protein kinase in liver WB-F344 cells. Arch. Toxicol. 73, 152-158.
75. Lahvis, G.P., Pyzalski, R.W., Glover, E., Pitot, H.C., McElwee, M.K., and Bradfield, C.A. (2005). The aryl hydrocarbon receptor is required for developmental closure of the ductus venosus in the neonatal mouse. Mol. Pharmacol. 67, 714-720.
76. Le Beau, M.M., Carver, L.A., Espinosa, R. III, Schmidt, J.V., and Bradfield, C.A. (1994). Chromosomal localization of the human AHR locus encoding the structural gene for the Ah receptor to 7p21™p15. Cytogenet. Cell Genet. 66, 172-176.
77. Li, W., Donat, S., Dohr, O., Unfried, K., and Abel, J. (1994). Ah receptor in different tissues of C57BL/6J and DBA/2J mice: use of competitive polymerase chain reaction to measure Ah-recep-tor mRNA expression. Arch. Biochem. Biophys. 315, 279-284.
78. Lin, T.M., Ko, K., Moore, R.W., Simanainen, U., Oberley, T.D., and Peterson, R.E. (2002). Effects of aryl hydrocarbon receptor null mutation and in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on prostate and seminal vesicle development in C57BL/6 mice. Toxicol. Sci. 68, 479-487.
79. Liu, P., Pazin, D.E., Merson, R.R., Albrecht, K.H., and Vaziri, C. (2009). The developmentally-regulated Smoc2 gene is repressed by aryl-hydrocarbon receptor (Ahr) signaling. Gene 433, 72-80.
80. Long, W.P., Chen, X., and Perdew, G.H. (1999). Protein kinase C modulates aryl hydrocarbon receptor nuclear translocator protein-mediated transactivation potential in a dimer context. J. Biol. Chem. 274, 12391-12400.
81. Lu, Y.F., Santostefano, M., Cunningham, B.D., Threadgill, M.D., and Safe, S. (1995). Identification of 39-methoxy-49-nitroflavone as a pure aryl hydrocarbon (Ah) receptor antagonist and evidence for more than one form of the nuclear Ah receptor in MCF-7 human breast cancer cells. Arch. Biochem. Biophys. 316, 470-477.
82. Luecke, S., Wincent, E., Backlund, M., Rannug, U., and Rannug, A. (2010). Cytochrome P450 1A1 gene regulation by UVB involves crosstalk between the aryl hydrocarbon receptor and nuclear factor kB. Chem. Biol. Interact. 184, 466-473.
83. Luo, G., Gu, Y.Z., Jain, S., Chan, W.K., Carr, K.M., Hogenesch, J.B., and Bradfield, C.A. (1997). Molecular characterization of the murine Hif-1a locus. Gene Expr. 6, 287-299.
84. Ma, Q. (2007). Aryl hydrocarbon receptor degradation-promoting factor (ADPF) and the control of the xenobiotic response. Mol. Intervent. 7, 133-137.
85. Ma, Q. and Baldwin, K.T. (2000). 2,3,7,8-Tetrachlorodibenzo-p-dioxin- induced degradation of aryl hydrocarbon receptor (AhR) by the ubiquitin-proteasome pathway. J. Biol. Chem. 275, 8432-8438.
86. Ma, Q. and Baldwin, K.T. (2002). A cycloheximide-sensitive factor regulates TCDD-induced degradation of the aryl hydrocarbon receptor. Chemosphere 46, 1491-1500.
87. Ma, Q. and Whitlock, J.P. (1997). A novel cytoplasmic protein that interacts with the Ah receptor contains tetratricopeptide repeat motifs and augments the transcriptional response to 2,3,7,8-tetra-chlorodibenzo-p-dioxin. J. Biol. Chem. 272, 8878-8884.
88. Machado, F.S., Johndrow, J.E., Esper, L., Dias, A., Bafica, A., Serhan, C.N., and Aliberti, J. (2006). Anti-inflammatory actions of lipoxin A4 and aspirin-triggered lipoxin are SOCS-2 dependent. Nat. Med. 12, 330-334.
89. Matikainen, T., Perez, G.I., Jurisicova, A., Pru, J.K., Schlezinger, J.J., Ryu, H.Y., Laine, J., Sakai, T., Korsmeyer, S.J., Casper, R.F., et al. (2001). Aromatic hydrocarbon receptor-driven Bax gene expression is required for premature ovarian failure caused by biohazardous environmental chemicals. Nat. Genet. 28, 355-360.
90. Matsumura, F. (2009). The significance of the nongenomic pathway in mediating inflammatory signaling of the dioxin-activated Ah receptor to cause toxic effects. Biochem. Pharmacol. 77, 608-626.
91. Medjakovic, S. and Jungbauer, A. (2008). Red clover isofla-vones biochanin A and formononetin are potent ligands of the human aryl hydrocarbon receptor. J. Steroid Biochem. Mol. Biol. 108, 171-177.
92. Merk, H.F., Abel, J., Baron, J.M., and Krutmann, J. (2004). Molecular pathways in dermatotoxicology. Toxicol. Appl. Pharmacol. 195, 267-277.
93. Mimura, J., Yamashita, K., Nakamura, K., Morita, M., Takagi, T. N., Nakao, K., Ema, M., Sogawa, K., Yasuda, M., Katsuki, M., et al. (1997). Loss of teratogenic response to 2,3,7,8-tetrachlo-rodibenzo-p-dioxin (TCDD) in mice lacking the Ah (dioxin) receptor. Genes Cells 2, 645-654.
94. Mimura, J., Ema, M., Sogawa, K., and Fujii-Kuriyama, Y. (1999). Identification of a novel mechanism of regulation of Ah (dioxin) receptor function. Genes Dev. 13, 20-25.
95. Mitchell, K.A. and Elferink, C.J. (2009). Timing is everything: consequences of transient and sustained AhR activity. Biochem. Pharmacol. 77, 947-956.
96. Munzel, P.A., Lehmkoster, T., Bruck, M., Ritter, J.K., and Bock, K.W. (1998). Aryl hydrocarbon receptor-inducible or constitutive expression of human UDP glucuronosyltransferase UGT1A6. Arch. Biochem. Biophys. 350, 72-78.
97. Murray, G.I. (2000). The role of cytochrome P450 in tumour development and progression and its potential in therapy. J. Pathol. 192, 419-426.
98. Nambu, J.R., Lewis, J.O., Wharton, K.A. Jr., and Crews, S.T. (1991). The Drosophila single-minded gene encodes a helix-loop-helix protein that acts as a master regulator of CNS midline development. Cell 67, 1157-1167.
99. Nishiumi, S., Yamamoto, N., Kodoi, R., Fukuda, I., Yoshida, K., and Ashida, H. (2008). Antagonistic and agonistic effects of indigoids on the transformation of an aryl hydrocarbon receptor. Arch. Biochem. Biophys. 470, 187-199.
100. Ogi, T., Mimura, J., Hikida, M., Fujimoto, H., Fujii-Kuriyama, Y., and Ohmori, H. (2001). Expression of human and mouse genes encoding polkappa: testis-specific developmental regulation and AhR-dependent inducible transcription. Genes Cells 6, 943-953.
101. Ohtake, F., Baba, A., Takada, I., Okada, M., Iwasaki, K., Miki, H., Takahashi, S., Kouzmenko, A., Nohara, K., Chiba, T., et al. (2007). Dioxin receptor is a ligand-dependent E3 ubiquitin ligase. Nature 446, 562-566.
102. Oshima, M., Mimura, J., Yamamoto, M., and Fujii-Kuriyama, Y. (2007). Molecular mechanism of transcriptional repression of AhR repressor involving ANKRA2, HDAC4, and HDAC5. Bio-chem. Biophys. Res. Commun. 364, 276-282.
103. Palermo, C.M., Westlake, C.A., and Gasiewicz, T.A. (2005). Epi-gallocatechin gallate inhibits aryl hydrocarbon receptor gene transcription through an indirect mechanism involving binding to a 90 kDa heat shock protein. Biochemistry 44, 5041-5052.
104. Patel, R.D., Kim, D.J., Peters, J.M., and Perdew, G.H. (2006). The aryl hydrocarbon receptor directly regulates expression of the potent mitogen epiregulin. Toxicol. Sci. 89, 75-82.
105. Pentland, A.P., Schoggins, J.W., Scott, G.A., Khan, K.N., and Han, R. (1999). Reduction of UV-induced skin tumors in hairless mice by selective COX-2 inhibition. Carcinogenesis 20, 1939-1944.
106. Phelan, D., Winter, G.M., Rogers, W.J., Lam, J.C., and Denison, M.S. (1998). Activation of the Ah receptor signal transduction pathway by bilirubin and biliverdin. Arch. Biochem. Biophys. 357, 155-163.
107. Pollenz, R.S. (1996). The aryl-hydrocarbon receptor, but not the aryl-hydrocarbon receptor nuclear translocator protein, is rapidly depleted in hepatic and nonhepatic culture cells exposed to 2,3,7,8-tetrachlorodibenzo-p- dioxin. Mol. Pharmacol. 49, 391-398.
108. Pollenz, R.S., Santostefano, M.J., Klett, E., Richardson, V.M., Nece-la, B., and Bimbaum, L.S. (1998). Female Sprague-Dawley rats exposed to a single oral dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin exhibit sustained depletion of aryl hydrocarbon receptor protein in liver, spleen, thymus, and lung. Toxicol. Sci. 42, 117-128.
109. Pongratz, I., Mason, G.G., and Poellinger, L. (1992). Dual roles of the 90-kDa heat shock protein hsp90 in modulating functional activities of the dioxin receptor. Evidence that the dioxin receptor functionally belongs to a subclass of nuclear receptors which require hsp90 both for ligand binding activity and repression of intrinsic DNA binding activity. J. Biol. Chem. 267, 13728-13734.
110. Probst, M.R., Reisz-Porszasz, S., Agbunag, R.V., Ong, M.S., and Hankinson, O. (1993). Role of the aryl hydrocarbon receptor nuclear translocator protein in aryl hydrocarbon (dioxin) receptor action. Mol. Pharmacol. 44, 511-518. (Pubitemid 23280260)
111. Puga, A., Maier, A., and Medvedovic, M. (2000). The transcrip-tional signature of dioxin in human hepatoma HepG2 cells. Bio-chem. Pharmacol. 60, 1129-1142.
112. Qin, H. and Powell-Coffman, J.A. (2004). The Caenorhabditis ele-gans aryl hydrocarbon receptor, AHR-1, regulates neuronal development. Dev. Biol. 270, 64-75.
113. Quattrochi, L.C. and Tukey, R.H. (1993). Nuclear uptake of the Ah (dioxin) receptor in response to omeprazole: transcriptional activation of the human CYP1A1 gene. Mol. Pharmacol. 43, 504-508.
114. H17 cell differentiation by the aryl hydrocarbon receptor. Nature 453, 65-71.
115. Rannug, A., Rannug, U., Rosenkranz, H.S., Winqvist, L., Weste-rholm, R., Agurell, E., and Grafstrom, A.K. (1987). Certain pho-tooxidized derivatives of tryptophan bind with very high affinity to the Ah receptor and are likely to be endogenous signal substances. J. Biol. Chem. 262, 15422-15427.
116. Rivera, S.P., Saarikoski, S.T., and Hankinson, O. (2002). Identification of a novel dioxin-inducible cytochrome P450. Mol. Pharmacol. 61, 255-259.
117. Romkes, M., Piskorska-Pliszczynska, J., and Safe, S. (1987). Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on hepatic and uterine estrogen receptor levels in rats. Toxicol. Appl. Pharmacol. 87, 306-314. (Pubitemid 17019115)
118. Rowlands, J.C., McEwan, I.J., and Gustafsson, J.A. (1996). Trans-activation by the human aryl hydrocarbon receptor and aryl hydrocarbon receptor nuclear translocator proteins: direct interactions with basal transcription factors. Mol. Pharmacol. 50, 538-548.
119. Rushmore, T.H. and Pickett, C.B. (1990). Transcriptional regulation of the rat glutathione S-transferase Ya subunit gene. Characterization of a xenobiotic-responsive element controlling inducible expression by phenolic antioxidants. J. Biol. Chem. 265, 14648-14653.
120. Safe, S. and Wormke, M. (2003). Inhibitory aryl hydrocarbon receptor-estrogen receptor a cross-talk and mechanisms of action. Chem. Res. Toxicol. 16, 807-816.
121. Schaldach, C.M., Riby, J., and Bjeldanes, L.F. (1999). Lipoxin A4: a new class of ligand for the Ah receptor. Biochemistry 38, 7594-7600.
122. Schmidt, J.V., Carver, L.A., and Bradfield, C.A. (1993). Molecular characterization of the murine Ahr gene. Organization, promoter analysis, and chromosomal assignment. J. Biol. Chem. 268, 22203-22209.
123. Schmidt, J.V., Su, G.H., Reddy, J.K., Simon, M.C., and Bradfield, C.A. (1996). Characterization of a murine Ahr null allele: involvement of the Ah receptor in hepatic growth and development. Proc. Natl. Acad. Sci. USA 93, 6731-6736.
124. Seidel, S.D., Winters, G.M., Rogers, W.J., Ziccardi, M.H., Li, V., Keser, B., and Denison, M.S. (2001). Activation of the Ah receptor signaling pathway by prostaglandins. J. Biochem. Mol. Toxi-col. 15, 187-196.
125. Sekine, H., Mimura, J., Oshima, M., Okawa, H., Kanno, J., Igarashi, K., Gonzalez, F.J., Ikuta, T., Kawajiri, K., and Fujii-Kuriyama, Y. (2009). Hypersensitivity of aryl hydrocarbon receptor-deficient mice to lipopolysaccharide-induced septic shock. Mol. Cell Biol. 29, 6391-6400.
126. Shimizu, Y., Nakatsuru, Y., Ichinose, M., Takahashi, Y., Kume, H., Mimura, J., Fujii-Kuriyama, Y., and Ishikawa, T. (2000). Ben-zowaxpyrene carcinogenicity is lost in mice lacking the aryl hydrocarbon receptor. Proc. Natl. Acad. Sci. USA 97, 779-782.
127. Shin, S., Wakabayashi, N., Misra, V., Biswal, S., Lee, G.H., Agos-ton, E.S., Yamamoto, M., and Kensler, T.W. (2007). NRF2 modulates aryl hydrocarbon receptor signaling: influence on adi-pogenesis. Mol. Cell. Biol. 27, 7188-7197.
128. Song, J., Clagett-Dame, M., Peterson, R.E., Hahn, M.E., Westler, W.M., Sicinski, R.R., and DeLuca, H.F. (2002). A ligand for the aryl hydrocarbon receptor isolated from lung. Proc. Natl. Acad. Sci. USA 99, 14694-14699.
129. Spink, B.C., Fasco, M.J., Gierthy, J.F., and Spink, D.C. (1998). 12-O-Tetradecanoylphorbol-13-acetate upregulates the Ah receptor and differentially alters CYP1B1 and CYP1A1 expression in MCF-7 breast cancer cells. J. Cell Biochem. 70, 289-296.
130. Stevens, E.A., Mezrich, J.D., and Bradfield, C.A. (2009). The aryl hydrocarbon receptor: a perspective on potential roles in the immune system. Immunology 127, 299-311.
131. Tan, K.P., Wang, B., Yang, M., Boutros, P.C., Macaulay, J., Xu, H., Chuang, A.I., Kazuhiro, K., Yamamoto, M., Takahashi, S., et al. (2010). Aryl hydrocarbon receptor (AHR) is a transcriptional activator of human breast cancer resistance protein (BCRP/ABCG2). Mol. Pharmacol. in press, DOI: 10.1124/mol.110. 065078.
132. Thackaberry, E.A., Gabaldon, D.M., Walker, M.K., and Smith, S.M. (2002). Aryl hydrocarbon receptor null mice develop cardiac hypertrophy and increased hypoxia-inducible factor-1alpha in the absence of cardiac hypoxia. Cardiovasc. Toxicol. 2, 263-274.
133. Thatcher, T.H., Maggirwar, S.B., Baglole, C.J., Lakatos, H.F., Gasie-wicz, T.A., Phipps, R.P., and Sime, P.J. (2007). Aryl hydrocarbon receptor-deficient mice develop heightened inflammatory responses to cigarette smoke and endotoxin associated with rapid loss of the nuclear factor-kB component RelB. Am. J. Pathol. 170, 855-864.
134. Tsuchiya, Y., Nakajima, M., Kyo, S., Kanaya, T., Inoue, M., and Yokoi, T. (2004). Human CYP1B1 is regulated by estradiol via estrogen receptor. Cancer Res. 64, 3119-3125.
135. Vanden Heuvel, J.P., Clark, G.C., Thompson, C.L., McCoy, Z., Miller, C.R., Lucier, G.W., and Bell, D.A. (1993). CYP1A1 mRNA levels as a human exposure biomarker: use of quantitative poly-merase chain reaction to measure CYP1A1 expression in human peripheral blood lymphocytes. Carcinogenesis 14, 2003-2006.
136. Veldhoen, M., Hirota, K., Westendorf, A.M., Buer, J., Dumoutier, L., Renauld, J.C., and Stockinger, B. (2008). The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature 453, 106-109.
137. Villard, P.H., Caverni, S., Baanannou, A., Khalil, A., Martin, P.G., Penel, C., Pineau, T., Seree, E., and Barra, Y. (2007). PPARa transcriptionally induces AhR expression in Caco-2, but represses AhR pro-inflammatory effects. Biochem. Biophys. Res. Commun. 364, 896-901.
138. Voeller, H.J., Truica, C.I., and Gelmann, E.P. (1998). b-Catenin mutations in human prostate cancer. Cancer Res. 58, 2520-2523.
139. Vrzal, R., Zdarilova, A., Ulrichova, J., Blaha, L., Giesy, J.P., and Dvorak, Z. (2005). Activation of the aryl hydrocarbon receptor by berberine in HepG2 and H4IIE cells: Biphasic effect on CYP1A1. Biochem. Pharmacol. 70, 925-936.
140. Wang, S. and Hankinson, O. (2002). Functional involvement of the Brahma/SWI2-related gene 1 protein in cytochrome P4501A1 transcription mediated by the aryl hydrocarbon receptor complex. J. Biol. Chem. 277, 11821-11827.
141. Wang, F., Gao, J.X., Mimura, J., Kobayashi, A., Sogawa, K., and Fujii-Kuriyama, Y. (1998). Structure and expression of the mouse AhR nuclear translocator (mArnt) gene. J. Biol. Chem. 273, 24867-24873.
142. Wang, F., Samudio, I., and Safe, S. (2001). Transcriptional activation of cathepsin D gene expression by 17b-estradiol: mechanism of aryl hydrocarbon receptor-mediated inhibition. Mol. Cell Endo-crinol. 172, 91-103. (Pubitemid 32101395)
143. Wei, Y.D., Helleberg, H., Rannug, U., and Rannug, A. (1998). Rapid and transient induction of CYP1A1 gene expression in human cells by the tryptophan photoproduct 6-formylindolow3,2-bx-carbazole. Chem. Biol. Interact. 110, 39-55.
144. 1. Mol. Pharmacol. 59, 716-724.
145. Wormke, M., Stoner, M., Saville, B., Walker, K., Abdelrahim, M., Burghardt, R., and Safe, S. (2003). The aryl hydrocarbon receptor mediates degradation of estrogen receptor a through activation of proteasomes. Mol. Cell Biol. 23, 1843-1855.
146. Yamamoto, J., Ihara, K., Nakayama, H., Hikino, S., Satoh, K., Kubo, N., Iida, T., Fujii, Y., and Hara, T. (2004). Characteristic expression of aryl hydrocarbon receptor repressor gene in human tissues: organ-specific distribution and variable induction patterns in mononuclear cells. Life Sci. 74, 1039-1049.
147. Yang, X., Liu, D., Murray, T.J., Mitchell, G.C., Hesterman, E.V., Karchner, S.I., Merson, R.R., Hahn, M.E., and Sherr, D.H. (2005). The aryl hydrocarbon receptor constitutively represses c-myc transcription in human mammary tumor cells. Oncogene 24, 7869-7881.
148. Yueh, M.F., Huang, Y.H., Hiller, A., Chen, S., Nguyen, N., and Tukey, R.H. (2003). Involvement of the xenobiotic response element (XRE) in Ah receptor-mediated induction of human UDP-glucuronosyltransferase 1A1. J. Biol. Chem. 278, 15001-15006.
149. Zhang, J., Watson, A.J., Probst, M.R., Minehart, E., and Hankinson, O. (1996). Basis for the loss of aryl hydrocarbon receptor gene expression in clones of a mouse hepatoma cell line. Mol. Pharmacol. 50, 1454-1462.
150. Zhang, L., Ma, J., Takeuchi, M., Usui, Y., Hattori, T., Okunuki, Y., Yamakawa, N., Kezuka, T., Kuroda, M., and Goto, H. (2010). Suppression of experimental autoimmune uveoretinitis by inducing differentiation of regulatory T cells via activation of aryl hydrocarbon receptor. Invest Ophthalmol. Vis. Sci. 51, 2109-2117.