Regulation of constitutive and inducible AHR signaling: Complex interactions involving the AHR repressor

Biochemical Pharmacology

Volumn 77, Issue 4, 2009, Pages 485-497

  Hahn, Mark E ^a   Allan, Lenka L ^b   Sherr, David H ^b  

^a WOODS HOLE OCEANOGRAPHIC INSTITUTION   (United States)

^b BOSTON UNIVERSITY SCHOOL OF PUBLIC HEALTH   (United States)

Author keywords

Aryl hydrocarbon receptor; Aryl hydrocarbon receptor repressor; Cancer; PAS proteins; Toxicology

Indexed keywords

AROMATIC HYDROCARBON RECEPTOR; AROMATIC HYDROCARBON RECEPTOR REPRESSOR; REPRESSOR PROTEIN; UNCLASSIFIED DRUG;

CARCINOGENESIS; COMPLEX FORMATION; HUMAN; MOLECULAR EVOLUTION; MOLECULAR RECOGNITION; NONHUMAN; PRIORITY JOURNAL; PROTEIN INDUCTION; PROTEIN POLYMORPHISM; PROTEIN PROTEIN INTERACTION; REPRODUCTION; REVIEW; SIGNAL TRANSDUCTION; TISSUE DISTRIBUTION; XENOBIOTIC METABOLISM;

ANIMALS; EMBRYONIC DEVELOPMENT; HUMANS; RECEPTORS, ARYL HYDROCARBON; REPRESSOR PROTEINS; SIGNAL TRANSDUCTION; SPECIES SPECIFICITY; TRANSCRIPTION, GENETIC; XENOBIOTICS;

EID: 59149097949     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bcp.2008.09.016     Document Type: Review

References (114)

1. Trombino A.F., Matulka R.A., Yang S., Hafer L.J., Rogers A.E., Tosselli P., et al. Expression of the aryl hydrocarbon receptor/transcription factor (AhR) and AhR-regulated CYP1 gene transcription in a rat model of mammary tumorigenesis. Breast Cancer Res Treat 62 (2000) 117-131
2. Currier N., Solomon S., Demicco E., Chang D., Farago M., Ying H., et al. Oncogenic signaling pathways activated in DMBA-induced mouse mammary tumors. Toxicol Pathol 33 (2005) 726
3. Yang X., Solomon S., Fraser L.R., Trombino A.F., Liu D., Sonenshein G.E., et al. Constitutive regulation of CYP1B1 by the aryl hydrocarbon receptor (AhR) in pre-malignant and malignant mammary tissue. J Cell Biochem 104 (2008) 402-417
4. Schlezinger J., Liu D., Farago M., Seldin D., Belguise K., Sonenshein G., et al. A role for the aryl hydrocarbon receptor in mammary gland tumorigenesis. Biol Chem 387 (2006) 1175-1187
5. Shin S.R., Sanchez-Velar N., Sherr D.H., and Sonenshein G.E. 7,12-Dimethylbenz(a)anthracene treatment of a c-rel mouse mammary tumor cell line induces epithelial to mesenchymal transition via activation of nuclear factor-kappaB. Cancer Res 66 (2006) 2570-2575
6. Belguise K., Guo S., Yang S., Rogers A.E., Seldin D.C., Sherr D.H., et al. Green tea polyphenols reverse cooperation between c-Rel and CK2 that induces the aryl hydrocarbon receptor, slug, and an invasive phenotype. Cancer Res 67 (2007) 11742-11750
7. Marshall N.B., Vorachek W.R., Steppan L.B., Mourich D.V., and Kerkvliet N.I. Functional characterization and gene expression analysis of CD4+ CD25+ regulatory T cells generated in mice treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin. J Immunol 181 (2008) 2382-2391
8. Funatake C.J., Marshall N.B., Steppan L.B., Mourich D.V., and Kerkvliet N.I. Cutting edge: activation of the aryl hydrocarbon receptor by 2,3,7,8-tetrachlorodibenzo-p-dioxin generates a population of CD4+ CD25+ cells with characteristics of regulatory T cells. J Immunol 175 (2005) 4184-4188
9. Quintana F.J., Basso A.S., Iglesias A.H., Korn T., Farez M.F., Bettelli E., et al. Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor. Nature (2008)
10. Gu Y.Z., Hogenesch J.B., and Bradfield C.A. The PAS superfamily: sensors of environmental and developmental signals. Annu Rev Pharmacol Toxicol 40 (2000) 519-561
11. Liu C., Goshu E., Wells A., and Fan C.M. Identification of the downstream targets of SIM1 and ARNT2, a pair of transcription factors essential for neuroendocrine cell differentiation. J Biol Chem 278 (2003) 44857-44867
12. Makino Y., Cao R., Svensson K., Bertilsson G., Asman M., Tanaka H., et al. Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression. Nature 414 (2001) 550-554
13. Moffett P., and Pelletier J. Different transcriptional properties of mSim-1 and mSim-2. FEBS Lett 466 (2000) 80-86
14. Ooe N., Saito K., Mikami N., Nakatuka I., and Kaneko H. Identification of a novel basic helix-loop-helix-PAS factor, NXF, reveals a Sim2 competitive, positive regulatory role in dendritic-cytoskeleton modulator drebrin gene expression. Mol Cell Biol 24 (2004) 608-616
15. Hankinson O. Role of coactivators in transcriptional activation by the aryl hydrocarbon receptor. Arch Biochem Biophys 433 (2005) 379-386
16. Harper P.A., Riddick D.S., and Okey A.B. Regulating the regulator: factors that control levels and activity of the aryl hydrocarbon receptor. Biochem Pharmacol 72 (2006) 267-279
17. Beischlag T.V., Luis Morales J., Hollingshead B.D., and Perdew G.H. The aryl hydrocarbon receptor complex and the control of gene expression. Crit Rev Eukaryot Gene Expr 18 (2008) 207-250
18. Allan L.L., and Sherr D.H. Constitutive activation and environmental chemical induction of the aryl hydrocarbon receptor/transcription factor in activated human B lymphocytes. Mol Pharmacol 67 (2005) 1740-1750
19. Levine-Fridman A., Chen L., and Elferink C.J. Cytochrome P4501A1 promotes G1 phase cell cycle progression by controlling aryl hydrocarbon receptor activity. Mol Pharmacol 65 (2004) 461-469
20. Yang X., Liu D., Murray T., Mitchell G., Hestermann D., Karchner S., et al. The aryl hydrocarbon receptor constitutively represses c-myc transcription in human mammary tumor cells. Oncogene 24 (2005) 7869
21. Murray S.A., Yang S., Demicco E., Ying H., Sherr D.H., Hafer L.J., et al. Increased expression of MDM2, cyclin D1, and p27(Kip1) in carcinogen-induced rat mammary tumors. J Cell Biochem (2005)
22. Murray T.J., Yang X., and Sherr D.H. Growth of a human mammary tumor cell line is blocked by galangin, a naturally occurring bioflavonoid, and is accompanied by down-regulation of cyclins D3, E, and A. Breast Cancer Res 8 (2006) R17
23. Puga A., Nebert D., and Carrier F. Dioxin induces expression of c-fos and c-jun proto-oncogenes and a large increase in transcription factor AP-1. DNA Cell Biol 11 (1992) 269-281
24. Sadhu D., Merchant M., Safe S., and Ramos K. Modulation of protooncogene expression in rat aortic smooth muscle cell by benzo[a]pyrene. Arch Biochem Biophys 300 (1993) 124-131
25. Ma Q., and Whitlock J. The aromatic hydrocarbon receptor modulates the Hepa 1c1c7 cell cycle and differentiated state independently of dioxin. Mol Cell Biol 16 (1996) 2144-2150
26. Abdelrahim M., Smith III R., and Safe S. Aryl hydrocarbon receptor gene silencing with small inhibitory RNA differentially modulates Ah-responsiveness in MCF-7 and HepG2 cancer cells. Mol Pharmacol 63 (2003) 1373-1381
27. Ray S.S., and Swanson H.I. Dioxin-induced immortalization of normal human keratinocytes and silencing of p53 and p16INK4a. J Biol Chem 279 (2004) 27187-27193
28. Elizondo G., Fernandez-Salguero P., Sheikh M.S., Kim G.Y., Fornace A.J., Lee K.S., et al. Altered cell cycle control at the G(2)/M phases in aryl hydrocarbon receptor-null embryo fibroblast. Mol Pharmacol 57 (2000) 1056-1063
29. Ito T., Tsukumo S., Suzuki N., Motohashi H., Yamamoto M., Fujii-Kuriyama Y., et al. A constitutively active arylhydrocarbon receptor induces growth inhibition of jurkat T cells through changes in the expression of genes related to apoptosis and cell cycle arrest. J Biol Chem 279 (2004) 25204-25210
30. Oenga G.N., Spink D.C., and Carpenter D.O. TCDD and PCBs inhibit breast cancer cell proliferation in vitro. Toxicol In Vitro 18 (2004) 811-819
31. Reiners Jr. J.J., Clift R., and Mathieu P. Suppression of cell cycle progression by flavonoids: dependence on the aryl hydrocarbon receptor. Carcinogenesis 20 (1999) 1561-1566
32. Park S., Mazina O., Kitagawa A., Wong P., and Matsumura F. TCDD causes suppression of growth and differentiation of MCF10A, human mammary epithelial cells by interfering with their insulin receptor signaling through c-Src kinase and ERK activation. J Biochem Mol Toxicol 18 (2004) 322-331
33. Kolluri S.K., Weiss C., Koff A., and Gottlicher M. p27(Kip1) induction and inhibition of proliferation by the intracellular Ah receptor in developing thymus and hepatoma cells. Genes Dev 13 (1999) 1742-1753
34. Puga A., Xia Y., and Elferink C. Role of the aryl hydrocarbon receptor in cell cycle regulation. Chem Biol Interact 141 (2002) 117-130
35. Keen J.C., and Davidson N.E. The biology of breast carcinoma. Cancer 97 (2003) 825-833
36. Singh S.S., Hord N.G., and Perdew G.H. Characterization of the activated form of the aryl hydrocarbon receptor in the nucleus of HeLa cells in the absence of exogenous ligand. Arch Biochem Biophys 329 (1996) 47-55
37. Hockings J.K., Thorne P.A., Kemp M.Q., Morgan S.S., Selmin O., and Romagnolo D.F. The ligand status of the aromatic hydrocarbon receptor modulates transcriptional activation of BRCA-1 promoter by estrogen. Cancer Res 66 (2006) 2224-2232
38. Guo J., Sartor M., Karyala S., Medvedovic M., Kann S., Puga A., et al. Expression of genes in the TGF-beta signaling pathway is significantly deregulated in smooth muscle cells from aorta of aryl hydrocarbon receptor knockout mice. Toxicol Appl Pharmacol 194 (2004) 79-89
39. Marlowe J.L., Knudsen E.S., Schwemberger S., and Puga A. The aryl hydrocarbon receptor displaces p300 from E2F-dependent promoters and represses S-phase specific gene expression. J Biol Chem 279 (2004) 29013-29022
40. Huang G., and Elferink C.J. Multiple mechanisms are involved in Ah receptor-mediated cell cycle arrest. Mol Pharmacol 67 (2005) 88-96
41. Marlowe J.L., Fan Y., Chang X., Peng L., Knudsen E.S., Xia Y., et al. The Ah receptor binds to E2F1 and inhibits E2F1-induced apoptosis. Mol Biol Cell 19 (2008) 3263-3271
42. Beischlag T.V., and Perdew G.H. ER alpha-AHR-ARNT protein-protein interactions mediate estradiol-dependent transrepression of dioxin-inducible gene transcription. J Biol Chem 280 (2005) 21607-21611
43. Reen R.K., Cadwallader A., and Perdew G.H. The subdomains of the transactivation domain of the aryl hydrocarbon receptor (AhR) inhibit AhR and estrogen receptor transcriptional activity. Arch Biochem Biophys 408 (2002) 93-102
44. Wormke M., Stoner M., Saville B., Walker K., Abdelrahim M., Burghardt R., et al. The aryl hydrocarbon receptor mediates degradation of estrogen receptor alpha through activation of proteasomes. Mol Cell Biol 23 (2003) 1843-1855
45. Ohtake F., Baba A., Takada I., Okada M., Iwasaki K., Miki H., et al. Dioxin receptor is a ligand-dependent E3 ubiquitin ligase. Nature 446 (2007) 562-566
46. Tian Y., Ke S., Thomas T., Meeker R., and Gallo M. Transcriptional suppression of estrogen receptor gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). J Steroid Biochem Mol Biol 67 (1998) 17-24
47. Duan R., Porter W., Samudio I., Vyhlidal C., Kladde M., and Safe S. Transcriptional activation of c-fos protooncogene by 17beta-estradiol: mechanism of aryl hydrocarbon receptor-mediated inhibition. Mol Endocrinol 13 (1999) 1511-1521
48. Porter W., Wang F., Duan R., Qin C., Castro-Rivera E., Kim K., et al. Transcriptional activation of heat shock protein 27 gene expression by 17beta-estradiol and modulation by antiestrogens and aryl hydrocarbon receptor agonists. J Mol Endocrinol 26 (2001) 31-42
49. Jeffy B.D., Chirnomas R.B., and Romagnolo D.F. Epigenetics of breast cancer: polycyclic aromatic hydrocarbons as risk factors. Environ Mol Mutagen 39 (2002) 235-244
50. Wu R., Zhang L., Hoagland M.S., and Swanson H.I. Lack of the aryl hydrocarbon receptor leads to impaired activation of AKT/protein kinase B and enhanced sensitivity to apoptosis induced via the intrinsic pathway. J Pharmacol Exp Ther 320 (2007) 448-457
51. Matikainen T., Perez G.I., Jurisicova A., Mann K.K., Schlezinger J.J., Ryu H.-T., et al. Aromatic hydrocarbon receptor-driven Bax gene expression is required for premature ovarian failure caused by biohazardous environmental chemicals. Nat Genet 28 (2001) 1-6
52. Matikainen T.M., Moriyama T., Morita Y., Perez G.I., Korsmeyer S.J., Sherr D.H., et al. Ligand activation of the aromatic hydrocarbon receptor transcription factor drives Bax-dependent apoptosis in developing fetal ovarian germ cells. Endocrinology 143 (2002) 615-620
53. Caruso J.A., Mathieu P.A., Joiakim A., Zhang H., and Reiners Jr. J.J. Aryl hydrocarbon receptor modulation of TNFalpha-induced apoptosis and lysosomal disruption in a hepatoma model that is caspase-8 independent. J Biol Chem 281 (2006) 10954-10967
54. Park K.T., Mitchell K.A., Huang G., and Elferink C.J. The aryl hydrocarbon receptor predisposes hepatocytes to Fas-mediated apoptosis. Mol Pharmacol 67 (2005) 612-622
55. Zudaire E., Cuesta N., Murty V., Woodson K., Adams L., Gonzalez N., et al. The aryl hydrocarbon receptor repressor is a putative tumor suppressor gene in multiple human cancers. J Clin Invest 118 (2008) 640-650
56. Miller M.E., Holloway A.C., and Foster W.G. Benzo-[a]-pyrene increases invasion in MDA-MB-231 breast cancer cells via increased COX-II expression and prostaglandin E2 (PGE2) output. Clin Exp Metastasis 22 (2005) 149-156
57. Mulero-Navarro S., Pozo-Guisado E., Perez-Mancera P.A., Alvarez-Barrientos A., Catalina-Fernandez I., Hernandez-Nieto E., et al. Immortalized mouse mammary fibroblasts lacking dioxin receptor have impaired tumorigenicity in a subcutaneous mouse xenograph model. J Biol Chem 280 (2005) 28731-28741
58. Min C., Eddy S.F., Sherr D.H., and Sonenshein G.E. NF-kappaB and epithelial to mesenchymal transition of cancer. J Cell Biochem 104 (2008) 733-744
59. Ikuta T., and Kawajiri K. Zinc finger transcription factor Slug is a novel target gene of aryl hydrocarbon receptor. Exp Cell Res 312 (2006) 3585-3594
60. Kanno Y., Takane Y., Izawa T., Nakahama T., and Inouye Y. The inhibitory effect of aryl hydrocarbon receptor repressor (AhRR) on the growth of human breast cancer MCF-7 Cells. Biol Pharm Bull 29 (2006) 1254-1257
61. Lahvis G.P., Pyzalski R.W., Glover E., Pitot H.C., McElwee M.K., and Bradfield C.A. The aryl hydrocarbon receptor is required for developmental closure of the ductus venosus in the neonatal mouse. Mol Pharmacol 67 (2005) 714-720
62. Walisser J.A., Glover E., Pande K., Liss A.L., and Bradfield C.A. Aryl hydrocarbon receptor-dependent liver development and hepatotoxicity are mediated by different cell types. Proc Natl Acad Sci USA 102 (2005) 17858-17863
63. Walisser J.A., Bunger M.K., Glover E., and Bradfield C.A. Gestational exposure of Ahr and Arnt hypomorphs to dioxin rescues vascular development. Proc Natl Acad Sci USA 101 (2004) 16677-16682
64. Veldhoen M., Hirota K., Westendorf A.M., Buer J., Dumoutier L., Renauld J.C., et al. The aryl hydrocarbon receptor links T(H)17-cell-mediated autoimmunity to environmental toxins. Nature (2008)
65. Hauben E., Gregori S., Draghici E., Migliavacca B., Olivieri S., Woisetschlager M., et al. Activation of the aryl hydrocarbon receptor promotes allograft specific tolerance through direct- and DC-mediated effects on regulatory T cells. Blood (2008)
66. Haarmann-Stemmann T., and Abel J. The arylhydrocarbon receptor repressor (AhRR): structure, expression, and function. Biol Chem 387 (2006) 1195-1199
67. Kawajiri K., and Fujii-Kuriyama Y. Cytochrome P450 gene regulation and physiological functions mediated by the aryl hydrocarbon receptor. Arch Biochem Biophys 464 (2007) 207-212
68. Mimura J., Ema M., Sogawa K., and Fujii-Kuriyama Y. Identification of a novel mechanism of regulation of Ah (dioxin) receptor function. Genes Dev 13 (1999) 20-25
69. Karchner S.I., Franks D.G., Powell W.H., and Hahn M.E. Regulatory interactions among three members of the vertebrate aryl hydrocarbon receptor family: AHR repressor, AHR1, and AHR2. J Biol Chem 277 (2002) 6949-6959
70. Evans B.R., Karchner S.I., Franks D.G., and Hahn M.E. Duplicate aryl hydrocarbon receptor repressor genes (ahrr1 and ahrr2) in the zebrafish Danio rerio: structure, function, evolution, and AHR-dependent regulation in vivo. Arch Biochem Biophys 441 (2005) 151-167
71. Nishihashi H., Kanno Y., Tomuro K., Nakahama T., and Inouye Y. Primary structure and organ-specific expression of the rat aryl hydrocarbon receptor repressor gene. Biol Pharm Bull 29 (2006) 640-647
72. Evans B.R., Karchner S.I., Allan L.L., Pollenz R.S., Tanguay R.L., Jenny M.J., et al. Repression of aryl hydrocarbon receptor (AHR) signaling by AHR repressor: role of DNA binding and competition for AHR nuclear translocator. Mol Pharmacol 73 (2008) 387-398
73. Korkalainen M., Tuomisto J., and Pohjanvirta R. Primary structure and inducibility by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) of aryl hydrocarbon receptor repressor in a TCDD-sensitive and a TCDD-resistant rat strain. Biochem Biophys Res Commun 315 (2004) 123-131
74. Nagase T., Kikuno R., Nakayama M., Hirosawa M., and Ohara O. Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res 7 (2000) 273-281
75. Zimmermann A.L., King E.A., Dengler E., Scogin S.R., and Powell W.H. An aryl hydrocarbon receptor repressor from Xenopus laevis: function, expression, and role in dioxin responsiveness during frog development. Toxicol Sci 104 (2008) 124-134
76. Roy N.K., Courtenay S.C., Chambers R.C., and Wirgin I.I. Characterization of the aryl hydrocarbon receptor repressor and a comparison of its expression in Atlantic tomcod from resistant and sensitive populations. Environ Toxicol Chem/SETAC 25 (2006) 560-571
77. Dehal P., Satou Y., Campbell R.K., Chapman J., Degnan B., De Tomaso A., et al. The draft genome of Ciona intestinalis: insights into chordate and vertebrate origins. Science 298 (2002) 2157-2167
78. Goldstone J.V., Hamdoun A., Cole B.J., Howard-Ashby M., Nebert D.W., Scally M., et al. The chemical defensome: environmental sensing and response genes in the Strongylocentrotus purpuratus genome. Dev Biol 300 (2006) 366-384
79. Hahn M.E., Karchner S.I., Evans B.R., Franks D.G., Merson R.R., and Lapseritis J.M. Unexpected diversity of aryl hydrocarbon receptors in non-mammalian vertebrates: insights from comparative genomics. J Exp Zool 305 (2006) 693-706
80. Baba T., Mimura J., Gradin K., Kuroiwa A., Watanabe T., Matsuda Y., et al. Structure and expression of the Ah receptor repressor gene. J Biol Chem 276 (2001) 33101-33110
81. Hahn M.E. The aryl hydrocarbon receptor: a comparative perspective. Comp Biochem Physiol 121 (1998) 23-53
82. Tsuchiya Y., Nakajima M., Itoh S., Iwanari M., and Yokoi T. Expression of aryl hydrocarbon receptor repressor in normal human tissues and inducibility by polycyclic aromatic hydrocarbons in human tumor-derived cell lines. Toxicol Sci 72 (2003) 253-259
83. Yamamoto J., Ihara K., Nakayama H., Hikino S., Satoh K., Kubo N., et al. Characteristic expression of aryl hydrocarbon receptor repressor gene in human tissues: organ-specific distribution and variable induction patterns in mononuclear cells. Life Sci 74 (2004) 1039-1049
84. Bernshausen T., Jux B., Esser C., Abel J., and Fritsche E. Tissue distribution and function of the aryl hydrocarbon receptor repressor (AhRR) in C57BL/6 and aryl hydrocarbon receptor deficient mice. Arch Toxicol 80 (2006) 206-211
85. Korkalainen M., Linden J., Tuomisto J., and Pohjanvirta R. Effect of TCDD on mRNA expression of genes encoding bHLH/PAS proteins in rat hypothalamus. Toxicology 208 (2005) 1-11
86. Aragon A.C., Kopf P.G., Campen M.J., Huwe J.K., and Walker M.K. In utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure: effects on fetal and adult cardiac gene expression and adult cardiac and renal morphology. Toxicol Sci 101 (2008) 321-330
87. Watanabe T., Imoto I., Kosugi Y., Fukuda Y., Mimura J., Fujii Y., et al. Human arylhydrocarbon receptor repressor (AHRR) gene: genomic structure and analysis of polymorphism in endometriosis. J Hum Genet 46 (2001) 342-346
88. Cauchi S., Stucker I., Cenee S., Kremers P., Beaune P., and Massaad-Massade L. Structure and polymorphisms of human aryl hydrocarbon receptor repressor (AhRR) gene in a French population: relationship with CYP1A1 inducibility and lung cancer. Pharmacogenetics 13 (2003) 339-347
89. Haarmann-Stemmann T., Bothe H., Kohli A., Sydlik U., Abel J., and Fritsche E. Analysis of the transcriptional regulation and molecular function of the aryl hydrocarbon receptor repressor in human cell lines. Drug Metab Dispos 35 (2007) 2262-2269
90. Fujita H., Kosaki R., Yoshihashi H., Ogata T., Tomita M., Hasegawa T., et al. Characterization of the aryl hydrocarbon receptor repressor gene and association of its Pro185Ala polymorphism with micropenis. Teratology 65 (2002) 10-18
91. Thackaberry E.A., Jiang Z., Johnson C.D., Ramos K.S., and Walker M.K. Toxicogenomic profile of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the murine fetal heart: modulation of cell cycle and extracellular matrix genes. Toxicol Sci 88 (2005) 231-241
92. Hosoya T., Harada N., Mimura J., Motohashi H., Takahashi S., Nakajima O., et al. Inducibility of cytochrome P450 1A1 and chemical carcinogenesis by benzo[a]pyrene in AhR repressor-deficient mice. Biochem Biophys Res Commun 365 (2008) 562-567
93. Jenny M.J., Karchner S.I., Franks D.G., Woodin B.R., and Hahn M.E. Roles of aryl hydrocarbon receptors (AHR) and AHR repressors in development and developmental toxicity of TCDD. Toxicol Sci 102 Suppl. (2008) 452
94. Gradin K., Toftgard R., Poellinger L., and Berghard A. Repression of dioxin signal transduction in fibroblasts. Identification of a putative repressor associated with Arnt. J Biol Chem 274 (1999) 13511-13518
95. Robles R., Morita Y., Mann K.K., Perez G.I., Yang S., Matikainen T., et al. The aryl hydrocarbon receptor, a basic helix-loop-helix transcription factor of the PAS gene family, is required for normal ovarian germ cell dynamics in the mouse. Endocrinology 141 (2000) 450-453
96. Peterson R.E., Theobald H.M., and Kimmel G.L. Developmental and reproductive toxicity of dioxins and related compounds: cross-species comparisons. Crit Rev Toxicol 23 (1993) 283-335
97. Hurst C.H., Abbott B., Schmid J.E., and Birnbaum L.S. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) disrupts early morphogenetic events that form the lower reproductive tract in female rat fetuses. Toxicol Sci 65 (2002) 87-98
98. Baba T., Mimura J., Nakamura N., Harada N., Yamamoto M., Morohashi K., et al. Intrinsic function of the aryl hydrocarbon (dioxin) receptor as a key factor in female reproduction. Mol Cell Biol 25 (2005) 10040-10051
99. Tsuchiya M., Katoh T., Motoyama H., Sasaki H., Tsugane S., and Ikenoue T. Analysis of the AhR, ARNT, and AhRR gene polymorphisms: genetic contribution to endometriosis susceptibility and severity. Fertil Steril 84 (2005) 454-458
100. Kim S.H., Choi Y.M., Lee G.H., Hong M.A., Lee K.S., Lee B.S., et al. Association between susceptibility to advanced stage endometriosis and the genetic polymorphisms of aryl hydrocarbon receptor repressor and glutathione-S-transferase T1 genes. Hum Reprod (Oxford, England) 22 (2007) 1866-1870
101. Soneda S., Fukami M., Fujimoto M., Hasegawa T., Koitabashi Y., and Ogata T. Association of micropenis with Pro185Ala polymorphism of the gene for aryl hydrocarbon receptor repressor involved in dioxin signaling. Endocr J 52 (2005) 83-88
102. Watanabe M., Sueoka K., Sasagawa I., Nakabayashi A., Yoshimura Y., and Ogata T. Association of male infertility with Pro185Ala polymorphism in the aryl hydrocarbon receptor repressor gene: implication for the susceptibility to dioxins. Fertil Steril 82 Suppl. 3 (2004) 1067-1071
103. Merisalu A., Punab M., Altmae S., Haller K., Tiido T., Peters M., et al. The contribution of genetic variations of aryl hydrocarbon receptor pathway genes to male factor infertility. Fertil Steril 88 (2007) 854-859
104. Tiido T., Rignell-Hydbom A., Jonsson B.A., Rylander L., Giwercman A., and Giwercman Y.L. Modifying effect of the AR gene trinucleotide repeats and SNPs in the AHR and AHRR genes on the association between persistent organohalogen pollutant exposure and human sperm Y:X ratio. Mol Hum Reprod 13 (2007) 223-229
105. Karchner S.I., Evans B.R., and Hahn M.E. Identification and functional analysis of a human AHR repressor. Toxicol Sci 96 Suppl. (2007) 190
106. Karchner S.I., Jenny M.J., Tarrant A.M., Evans B.R., Yang X., Sherr D.H., et al. Aryl hydrocarbon receptor repressor (AHRR): mechanistic insights from studies in mammalian and nonmammalian models. Toxicol Sci 102 Suppl. (2008) 451
107. Nebert D.W., Puga A., and Vasiliou V. Role of the Ah receptor and the dioxin-inducible [Ah] gene battery in toxicity, cancer, and signal transduction. Ann N Y Acad Sci 685 (1993) 624-640
108. Kanno Y., Takane Y., Takizawa Y., and Inouye Y. Suppressive effect of aryl hydrocarbon receptor repressor on transcriptional activity of estrogen receptor alpha by protein-protein interaction in stably and transiently expressing cell lines. Mol Cell Endocrinol 291 (2008) 87-94
109. Wang F., Samudio I., and Safe S. Transcriptional activation of cathepsin D gene expression by 17beta-estradiol: mechanism of aryl hydrocarbon receptor-mediated inhibition. Mol Cell Endocrinol 172 (2001) 91-103
110. Oshima M., Mimura J., Yamamoto M., and Fujii-Kuriyama Y. Molecular mechanism of transcriptional repression of AhR repressor involving ANKRA2, HDAC4, and HDAC5. Biochem Biophys Res Commun 364 (2007) 276-282
111. Kanno Y., Miyama Y., Takane Y., Nakahama T., and Inouye Y. Identification of intracellular localization signals and of mechanisms underlining the nucleocytoplasmic shuttling of human aryl hydrocarbon receptor repressor. Biochem Biophys Res Commun 364 (2007) 1026-1031
112. Evans B.R., Allan L.L., Sherr D.H., and Hahn M.E. DRE binding is not required for repression of AhR signaling by AhRR. Toxicol Sci 84 Supplement (2006) 278
113. Sogawa K., Numayama-Tsuruta K., Takahashi T., Matsushita N., Miura C., Nikawa J., et al. A novel induction mechanism of the rat CYP1A2 gene mediated by Ah receptor-Arnt heterodimer. Biochem Biophys Res Commun 318 (2004) 746-755
114. Kikuchi Y., Ohsawa S., Mimura J., Ema M., Takasaki C., Sogawa K., et al. Heterodimers of bHLH-PAS protein fragments derived from AhR, AhRR, and Arnt prepared by co-expression in Escherichia coli: characterization of their DNA binding activity and preparation of a DNA complex. J Biochem (Tokyo) 134 (2003) 83-90