Overview of AHR Functional Domains and the Classical AHR Signaling Pathway: Induction of Drug Metabolizing Enzymes

The AH Receptor in Biology and Toxicology

Volumn , Issue , 2011, Pages 33-45

  Ma, Qiang ^a  

^a NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH   (United States)

Author keywords

AHR domains, signaling pathway; AHR, ligand activated factor; CYP1A1 induction, drug metabolizing

Indexed keywords

EID: 80053029627     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9781118140574.ch2     Document Type: Chapter

References (90)

1. Whitlock, J. P., Jr. (1999). Induction of cytochrome P4501A1. Annual Reviews in Pharmacology and Toxicology, 39, 103-125.
2. Conney, A. H. (1982). Induction of microsomal enzymes by foreign chemicals and carcinogenesis by polycyclic aromatic hydrocarbons: G. H. A. Clowes Memorial Lecture. Cancer Research, 42, 4875-4917.
3. Ma, Q. and Lu, A. Y. (2007). CYP1A induction and human risk assessment: an evolving tale of in vitro and in vivo studies. Drug Metabolism and Disposition, 35, 1009-1016.
4. Poland, A. and Knutson, J. C. (1982). 2,3,7,8-Tetrachlorodibenzo-p-dioxin and related halogenated aromatic hydrocarbons: examination of the mechanism of toxicity. Annual Reviews in Pharmacology and Toxicology, 22, 517-554.
5. 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. Toxicology and Applied Pharmacology, 140, 173-179.
6. White, S. S. and Birnbaum, L. S. (2009). An overview of the effects of dioxins and dioxin-like compounds on vertebrates, as documented in human and ecological epidemiology. Journal of Environmental Science and Health, Part C, 27, 197-211.
7. 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. Molecular Pharmacology, 67, 714-720.
8. Zaher, H., Fernandez-Salguero, P. M., Letterio, J., Sheikh, M. S., Fornace, A. J., Jr., Roberts, A. B., and Gonzalez, F. J. (1998). The involvement of aryl hydrocarbon receptor in the activation of transforming growth factor-beta and apoptosis. Molecular Pharmacology, 54, 313-321.
9. Bock, K. W. and Kohle, C. (2009). The mammalian aryl hydrocarbon (Ah) receptor: from mediator of dioxin toxicity toward physiological functions in skin and liver. Biological Chemistry, 390, 1225-1235.
10. Esser, C., Rannug, A., and Stockinger, B. (2009). The aryl hydrocarbon receptor in immunity. Trends in Immunology, 30, 447-454.
11. Singh, K. P., Casado, F. L., Opanashuk, L. A., and Gasiewicz, T. A. (2009). The aryl hydrocarbon receptor has a normal function in the regulation of hematopoietic and other stem/progenitor cell populations. Biochemical Pharmacology, 77, 577-587.
12. Ma, Q. and Whitlock, J. P., Jr. (1996). The aromatic hydrocarbon receptor modulates the Hepa 1c1c7 cell cycle and differentiated state independently of dioxin. Molecular and Cellular Biology, 16, 2144-2150.
13. Ma, Q. (2008). Ah receptor: xenobiotic response meets inflammation. Blood, 112, 928-929.
14. 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.
15. Ma, Q. and Lu, A. Y. H. (2008). The challenges of dealing with promiscuous drug-metabolizing enzymes, receptors and transporters. Current Durg Metabolism, 9, 374-383.
16. Ma, Q. (2008). Xenobiotic-activated receptors: from transcription to drug metabolism to disease. Chemical Research in Toxicology, 21, 1651-1671.
17. Denison, M. S., Fisher, J. M., and Whitlock, J. P., Jr. (1988). Inducible, receptor-dependent protein-DNA interactions at a dioxin-responsive transcriptional enhancer. Proceedings of the National Academy of Sciences of the United States of America, 85, 2528-2532.
18. Strom, D. K., Postlind, H., and Tukey, R. H. (1992). Characterization of the rabbit CYP1A1 and CYP1A2 genes: developmental and dioxin-inducible expression of rabbit liver P4501A1 and P4501A2. Archives of Biochemistry and Biophysics, 294, 707-716.
19. Nukaya, M., Moran, S., and Bradfield, C. A. (2009). The role of the dioxin-responsive element cluster between the Cyp1a1 and Cyp1a2 loci in aryl hydrocarbon receptor biology. Proceedingsof the National Academy of Sciences of the United States of America, 106, 4923-4928.
20. Sutter, T. R., Tang, Y. M., Hayes, C. L., Wo, Y. Y., Jabs, E. W., Li, X., Yin, H., Cody, C. W., and Greenlee, W. F. (1994). Complete cDNA sequence of a human dioxin-inducible mRNA identifies a new gene subfamily of cytochrome P450 that maps to chromosome 2. Journal of Biological Chemistry, 269, 13092-13099.
21. Zhang, L., Savas, U., Alexander, D. L., and Jefcoate, C. R. (1998). Characterization of the mouse Cyp1B1 gene. Identification of an enhancer region that directs aryl hydrocarbon receptor-mediated constitutive and induced expression. Journal of Biological Chemistry, 273, 5174-5183.
22. Rivera, S. P., Wang, F., Saarikoski, S. T., Taylor, R. T., Chapman, B., Zhang, R., and Hankinson, O. (2007). A novel promoter element containing multiple overlapping xenobiotic and hypoxia response elements mediates induction of cytochrome P4502S1 by both dioxin and hypoxia. Journal of Biological Chemistry, 282, 10881-10893.
23. 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. Molecular Pharmacology, 67, 1325-1333.
24. Lamsa, V., Levonen, A. L., Leinoene, H., Yla-Herttuala, S., Yamamoto, M., and Hakkola, J. (2010). Cytochrome P450 2A5 constitutive expression and induction by heavy metals is dependent on redox-sensitive transcription factor Nrf2 in liver. Chemical Research in Toxicology, 23, 977-985.
25. Rushmore, T. H., King, R. G., Paulson, K. E., and Pickett, C. B. (1990). Regulation of glutathione S-transferaseYa subunit gene expression: identification of a unique xenobiotic-responsive element controlling inducible expression by planar aromatic compounds. Proceedings of the National Academy of Sciences of the United States of America, 87, 3826-3830.
26. 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. Journal of Biological Chemistry, 265, 14648-14653.
27. 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. Journal of Biological Chemistry, 278, 15001-15006.
28. Yueh, M. F. and Tukey, R. H. (2007). Nrf2-Keap1 signaling pathway regulates human UGT1A1 expression in vitro and in transgenic UGT1 mice. Journal of Biological Chemistry, 282, 8749-8758.
29. Emi, Y., Ikushiro, S., and Iyanagi, T. (1996). Xenobiotic responsive element-mediated transcriptional activation in the UDP-glucuronosyltransferase family 1 gene complex. Journal of Biological Chemistry, 271, 3952-3958.
30. Munzel, P. A., Schmohl, S., Heel, H., Kalberer, K., Bock-Hennig, B. S., and Bock, K. W. (1999). Induction of human UDP glucuronosyltransferases (UGT1A6, UGT1A9, and UGT2B7) by t-butylhydroquinone and 2,3,7,8-tetrachlorodi-benzo-p-dioxin in Caco-2 cells. Drug Metabolism and Disposition, 27, 569-573.
31. Munzel, P. A., Schmohl, S., Buckler, F., Jaehrling, J., Raschko, F. T.,Kohle, C., and Bock, K.W. (2003). Contribution of the Ah receptor to the phenolic antioxidant-mediated expression of human and rat UDP-glucuronosyltransferase UGT1A6 in Caco-2 and rat hepatoma 5L cells. Biochemical Pharmacology, 66, 841-847.
32. Favreau, L. V. and Pickett, C. B. (1991). Transcriptional regulation of the rat NAD(P)H:quinone reductase gene. Identification of regulatory elements controlling basal level expression and inducible expression by planar aromatic compounds and phenolic antioxidants. Journal of Biological Chemistry, 266, 4556-4561.
33. Vasiliou,V., Reuter, S. F.,Williams, S., Puga, A., and Nebert, D. W. (1999). Mouse cytosolic class 3 aldehyde dehydrogenase (Aldh3a1): gene structure and regulation of constitutive and dioxin-inducible expression. Pharmacogenetics, 9, 569-580.
34. Maher, J. M., Cheng, X., Slitt, A. L., Dieter, M. Z., and Klaassen, C. D. (2005). Induction of the multidrug resistance-associated protein family of transporters by chemical activators of receptor-mediated pathways in mouse liver. Drug Metabolism and Disposition, 33, 956-962.
35. Uno, S., Dalton, T. P., Dragin, N., Curran, C. P., Derkenne, S., Miller, M. L., Shertzer, H. G., Gonzalez, F. J., and Nebert, D. W. (2006). Oral benzo[a]pyrene in Cyp1 knockout mouse lines: CYP1A1 important in detoxication, CYP1B1 metabolism required for immune damage independent of total-body burden and clearance rate. Molecular Pharmacology, 69, 1103-1114.
36. Richardson, H. L., Stier, A. R., and Borsos-Nachtnebel, E. (1952). Liver tumor inhibition and adrenal histologic responses in rats to which 30-methyl-4-dimethylaminoazobenzene and 20-methylcholanthrene were simultaneously administered. Cancer Research, 12, 356-361.
37. Conney, A. H., Miller, E. C., and Miller, J. A. (1956). The metabolism of methylated aminoazo dyes. V. Evidence for induction of enzyme synthesis in the rat by 3-methylcholanthrene. Cancer Research, 16, 450-459.
38. Conney,A.H. (2003). Induction of drug-metabolizing enzymes: a path to the discovery of multiple cytochromes P450. Annual Review of Pharmacology and Toxicology, 43, 1-30.
39. Gielen, J. E., Goujon, F. M., and Nebert, D.W. (1972). Genetic regulation of aryl hydrocarbon hydroxylase induction. II. Simple Mendelian expression in mouse tissues in vivo. Journal of Biological Chemistry, 247, 1125-1137.
40. Thomas, P. E., Kouri, R. E., and Hutton, J. J. (1972). The genetics of aryl hydrocarbon hydroxylase induction in mice: a single gene difference between C57BL-6J and DBA-2J. Biochemical Genetics, 6, 157-168.
41. Poland, A. and Glover, E. (1974). Comparison of 2,3,7,8-tetrachlorodibenzo-p-dioxin, a potent inducer of aryl hydrocarbon hydroxylase, with 3-methylcholanthrene. Molecular Pharmacology, 10, 349-359.
42. Poland, A. and Glover, E. (1975). Genetic expression of aryl hydrocarbon hydroxylase by 2,3,7,8-tetrachlorodibenzop-dioxin: evidence for a receptor mutation in genetically nonresponsive mice. Molecular Pharmacology, 11, 389-398.
43. Poland, A., Glover, E., and Kende, A. S. (1976). Stereospecific, high affinity binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin by hepatic cytosol. Evidence that the binding species is receptor for induction of aryl hydrocarbon hydroxylase. Journal of Biological Chemistry, 251, 4936-4946.
44. Whitlock, J. P., Jr. (1990). Genetic and molecular aspects of 2,3,7,8-tetrachlorodibenzo-p-dioxin action. Annual Review of Pharmacology and Toxicology, 30, 251-277.
45. Hankinson, O. (1995). The aryl hydrocarbon receptor complex. Annual Review of Pharmacology and Toxicology, 35, 307-340.
46. Okino, S. T. and Whitlock, J. P., Jr. (1995). Dioxin induces localized, graded changes in chromatin structure: implications for Cyp1A1 gene transcription. Molecular and Cellular Biology, 15, 3714-3721.
47. Bradfield, C. A., Glover, E., and Poland, A. (1991). Purification and N-terminal amino acid sequence of the Ah receptor from the C57BL/6J mouse. Molecular Pharmacology, 39, 13-19.
48. Burbach, K. M., Poland, A., and Bradfield, C. A. (1992). Cloning of the Ah-receptor cDNA reveals a distinctive ligandactivated transcription factor. Proceedings of the National Academy of Sciences of the United States of America, 89, 8185-8189.
49. Ma, Q. and Whitlock, J. P., Jr. (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-tetrachlorodibenzo-p-dioxin. Journal of Biological Chemistry, 272, 8878-8884.
50. Ma, Q., Dong, L., and Whitlock, J. P., Jr. (1995). Transcriptional activation by the mouse Ah receptor. Interplay between multiple stimulatory and inhibitory functions. Journal of Biological Chemistry, 270, 12697-12703.
51. Hoffman, E. C., Reyes, H., Chu, F. F., Sander, F., Conley, L. H., Brooks, B. A., and Hankinson, O. (1991). Cloning of a factor required for activity of the Ah (dioxin) receptor. Science, 252, 954-958.
52. Reyes, H., Reisz-Porszasz, S., and Hankinson, O. (1992). Identification of the Ah receptor nuclear translocator protein (Arnt) as a component of the DNA binding form of the Ah receptor. Science, 256, 1193-1195.
53. Ko, H. P., Okino, S. T., Ma, Q., and Whitlock, J. P., Jr. (1996). Dioxin-induced CYP1A1 transcription in vivo: the aromatic hydrocarbon receptor mediates transactivation, enhancerpromoter communication, and changes in chromatin structure. Molecular and Cellular Biology, 16, 430-436.
54. Ko, H. P., Okino, S. T., Ma, Q., and Whitlock, J. P., Jr. (1997). Transactivation domains facilitate promoter occupancy for the dioxin-inducible CYP1A1 gene in vivo. Molecular and Cellular Biology, 17, 3497-3507.
55. Carver, L. A., Jackiw, V., and Bradfield, C. A. (1994). The 90-kDa heat shock protein is essential for Ah receptor signaling in a yeast expression system. Journal of Biological Chemistry, 269, 30109-30112.
56. Whitelaw,M. L., McGuire, J., Picard, D., Gustafsson, J. A., and Poellinger, L. (1995). Heat shock protein hsp90 regulatesdioxin receptor function in vivo. Proceedings of the National Academy of Sciences of the United States of America, 92, 4437-4441.
57. Carver, L. A. and Bradfield, C. A. (1997). Ligand-dependent interaction of the aryl hydrocarbon receptor with a novel immunophilin homolog in vivo. Journal of Biological Chemistry, 272, 11452-11456.
58. Meyer, B. K., Pray-Grant, M. G., Vanden Heuvel, J. P., and Perdew, G. H. (1998). Hepatitis B virus X-associated protein 2 is a subunit of the unliganded aryl hydrocarbon receptor core complex and exhibits transcriptional enhancer activity. Molecular and Cellular Biology, 18, 978-988.
59. Lin, B. C., Nguyen, L. P., Walisser, J. A., and Bradfield, C. A. (2008). A hypomorphic allele of aryl hydrocarbon receptorassociated protein-9 produces a phenocopy of the AHR-null mouse. Molecular Pharmacology, 74, 1367-1371.
60. Ma, Q. and Baldwin, K. T. (2000). 2, 3,7,8-Tetrachlorodibenzop-dioxin-induced degradation of aryl hydrocarbon receptor (AhR) by the ubiquitin-proteasome pathway. Role of the transcription activation and DNA binding of AhR. Journal of Biological Chemistry, 275, 8432-8438.
61. Lusska, A., Wu, L., and Whitlock, J. P., Jr. (1992). Superinduction of CYP1A1 transcription by cycloheximide. Role of the DNA binding site for the liganded Ah receptor. Journal of Biological Chemistry, 267, 15146-15151.
62. Ma, Q., Renzelli, A. J., Baldwin, K. T., and Antonini, J. M. (2000). Superinduction of CYP1A1 gene expression. Regulation of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced degradation of Ah receptor by cycloheximide. Journal of Biological Chemistry, 275, 12676-12683.
63. Ma, Q. (2002). Induction and superinduction of 2,3,7,8-tetrachlorodibenzo-rho-dioxin-inducible poly(ADP-ribose) polymerase: role of the aryl hydrocarbon receptor/aryl hydrocarbon receptor nuclear translocator transcription activation domains and a labile transcription repressor. Archives of Biochemistry and Biophysics, 404, 309-316.
64. Ma, Q. and Baldwin, K. T. (2002). A cycloheximide-sensitive factor regulates TCDD-induced degradation of the aryl hydrocarbon receptor. Chemosphere, 46, 1491-1500.
65. Ma, Q. (2007). Aryl hydrocarbon receptor degradationpromoting factor (ADPF) and the control of the xenobiotic response. Molecular Interventions, 7, 133-137.
66. Talalay, P., Dinkova-Kostova, A. T., and Holtzclaw, W. D. (2003). Importance of phase 2 gene regulation in protection against electrophile and reactive oxygen toxicity and carcinogenesis. Advances in Enzyme Regulation, 43, 121-134.
67. Ma, Q. (2010). Transcriptional responses to oxidative stress: pathological and toxicological implications. Pharmacological Therapy, 125, 376-393.
68. Ma, Q., Kinneer, K., Bi, Y., Chan, J. Y., and Kan, Y.W. (2004). Induction of murine NAD(P)H:quinone oxidoreductase by 2,3,7,8-tetrachlorodibenzo-p-dioxin requires the CNC (cap 'n' collar) basic leucine zipper transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2): cross-interaction between AhR (aryl hydrocarbon receptor) and Nrf2 signal transduction. Biochemical Journal, 377, 205-213.
69. Wang, G. L., Jiang, B. H., Rue, E. A., and Semenza, G. L. (1995). Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellularO2 tension. Proceedings of the National Academy of Sciences of the United States of America, 92, 5510-5514.
70. Fleming, C. R., Billiard, S. M., and Di Giulio, R. T. (2009). Hypoxia inhibits induction of aryl hydrocarbon receptor activity in topminnow hepatocarcinoma cells in an ARNT-dependent manner. Comparative Biochemistry and Physiology, Part C, 150, 383-389.
71. Hofer, T., Pohjanvirta, R., Spielmann, P., Viluksela, M., Buchmann, D. P., Wenger, R. H., and Gassmann, M. (2004). Simultaneous exposure of rats to dioxin and carbon monoxide reduces the xenobiotic but not the hypoxic response. Biological Chemistry, 385, 291-294.
72. Ruegg, J., Swedenborg, E., Wahlstrom, D., Escande, A., Balaguer, P., Pettersson, K., and Pongratz, I. (2008). The transcription factor aryl hydrocarbon receptor nuclear translocator functions as an estrogen receptor beta-selective coactivator, and its recruitment to alternative pathways mediates antiestrogenic effects of dioxin. Molecular Endocrinology, 22, 304-316.
73. Ke, S., Rabson, A. B., Germino, J. F., Gallo, M. A, and Tian, Y. (2001). Mechanism of suppression of cytochrome P-450 1A1 expression by tumor necrosis factor-alpha and lipopolysaccharide. Journal of Biological Chemistry, 276, 39638-39644.
74. Kim, D.W., Gazourian, L., Quadri, S. A., Romieu-Mourez, R., Sherr, D. H., and Sonenshein, G. E. (2000). The RelA NFkappaB subunit and the aryl hydrocarbon receptor (AhR) cooperate to transactivate the c-myc promoter in mammary cells. Oncogene, 19, 5498-5506.
75. Denison, M. S., and Nagy, S. R. (2003). Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals. Annual Review of Pharmacology and Toxicology, 43, 309-334.
76. Nguyen, L. P. and Bradfield, C. A. (2008). The search for endogenous activators of the aryl hydrocarbon receptor. Chemical Research in Toxicology, 21, 102-116.
77. 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., Sherr, D. H., and Tilly, J. L. (2001). Aromatic hydrocarbon receptor-driven Bax gene expression is required for premature ovarian failure caused by biohazardous environmental chemicals. Nature Genetics, 28, 355-360.
78. Krishnan, V., Porter,W., Santostefano, M.,Wang, X., and Safe, S. (1995). Molecular mechanism of inhibition of estrogeninduced cathepsin D gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in MCF-7 cells. Molecular and Cellular Biology, 15, 6710-6719.
79. Baba, T., Mimura, J., Gradin, K., Kuroiwa, A., Watanabe, T., Matsuda, Y., Inazawa, J., Sogawa, K., and Fujii-Kuriyama, Y. (2001). Structure and expression of the Ah receptor repressor gene. Journal of Biological Chemistry, 276, 33101-33110.
80. 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 repressesc-myc transcription in human mammary tumor cells. Oncogene, 24, 7869-7881.
81. Gillesby, B. E., Stanostefano, M., Porter,W., Safe, S.,Wu, Z. F., and Zacharewski, T. R. (1997). Identification of a motif within the 50 regulatory region of pS2 which is responsible for AP-1 binding and TCDD-mediated suppression. Biochemistry, 36, 6080-6089.
82. Sulentic, C. E., Holsapple, M. P., and Kaminski, N. E. (2000). Putative link between transcriptional regulation of IgM expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin and the aryl hydrocarbon receptor/dioxin-responsive enhancer signaling pathway. Journal of Pharmacology and Experimental Therapeutics, 295, 705-716.
83. Jeon, M. S. and Esser, C. (2000). The murine IL-2 promoter contains distal regulatory elements responsive to the Ah receptor, a member of the evolutionarily conserved bHLH-PAS transcription factor family. Journal of Immunology, 165, 6975-6983.
84. Marchand, A., Tomkiewicz, C., Marchandeau, J. P., Boitier, E., Barouki, R., and Garlatti, M. (2005). 2, 3,7,8-Tetrachlorodibenzo-p-dioxin induces insulin-like growth factor binding protein-1 gene expression and counteracts the negative effect of insulin. Molecular Pharmacology, 67, 444-452.
85. Kolluri, S. K., Weiss, C., Koff, A., and Gottlicher, M. (1999). p27(Kip1) induction and inhibition of proliferation by theintracellular Ah receptor in developing thymus and hepatoma cells. Genes & Development, 13, 1742-1753.
86. Barnes-Ellerbe,S.,Knudsen, andK.E., Puga, A. (2004). 2, 3,7,8-Tetrachlorodibenzo-p-dioxin blocks androgen-dependent cell proliferation of LNCaP cells through modulation of pRB phosphorylation. Molecular Pharmacology, 66, 502-511.
87. McMillan, B. J., McMillan, S. N., Glover, E., and Bradfield, C. A. (2007). 2, 3,7,8-Tetrachlorodibenzo-p-dioxin induces premature activation of the KLF2 regulon during thymocyte development. Journal of Biological Chemistry, 282, 12590-12597.
88. Ma, Q., Baldwin, K. T., Renzelli, A. J., McDaniel, A., and Dong, L. (2001). TCDD-inducible poly(ADP-ribose) polymerase: a novel response to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Biochemical and Biophysical Research Communications, 289, 499-506.
89. Dong, L., Ma, Q., and Whitlock, J. P., Jr. (1997). Downregulation of major histocompatibility complex Q1b gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Journal of Biological Chemistry, 272, 29614-29619.
90. Lawrence, B. P., Denison, M. S., Novak, H., Vorderstrasse, B. A., Harrer, N., Neruda, W., Reichel, C., and Woisetschlager, M. (2008). Activation of the aryl hydrocarbon receptor is essential for mediating the anti-inflammatory effects of a novel low-molecular-weight compound. Blood, 112, 1158-1165.