Cytochrome P450 gene regulation and physiological functions mediated by the aryl hydrocarbon receptor
Abstract
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that functions as an intracellular mediator in the xenobiotic signaling pathway. Although a number of studies have examined AhR-mediated CYP1A1 induction in detail, recent studies of AhR-null mice have revealed that AhR plays important regulatory roles in the normal homeostasis and development of animals. In this short review, we summarize the present state of knowledge about the molecular mechanisms of AhR-mediated CYP1 induction, and we also focus on recent advances in the study of the physiological functions of AhR.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Two up-regulated P450s, CYP1A1 and CYP2S1, are known to be regulated by the aryl hydrocarbon receptor.
“Two of them (CYP1A1 and CYP2S1) are known to be regulated by the aryl hydrogen receptor (25, 26).”
From Comparative proteomic phenotyping of cell lines and primary cells to assess preservation of cell type-specific functions (2009) · cites this paper as [25]
The aryl hydrocarbon receptor was more highly expressed in Hepa1-6, providing an explanation for the up-regulation of CYP1A1 and CYP2S1.
“This receptor was also more highly expressed in Hepa1–6, providing a ready explanation for the up-regulation.”
From Comparative proteomic phenotyping of cell lines and primary cells to assess preservation of cell type-specific functions (2009) · cites this paper as [25]
Cites
The Aryl Hydrocarbon Receptor Complex
Hankinson, O. (1995) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pa.35.040195.001515 · Cited by 1,649 · see citing works
Immune System Impairment and Hepatic Fibrosis in Mice Lacking the Dioxin-Binding Ah Receptor
Fernandez-Salguero, P., Pineau, T., Hilbert, D. M., McPhail, T., Lee, S. S. T., Kimura, S., Nebert, D. W., Rudikoff, S., Ward, J. M., & Gonzalez, F. J. (1995) · Science · doi:10.1126/science.7732381 · Cited by 1,075 · see citing works
Nebert, D. W., & Dalton, T. P. (2006) · Nature reviews. Cancer · doi:10.1038/nrc2015 · Cited by 959 · see citing works
Schmidt, J. V., Su, G. H., Reddy, J., Simon, M., & Bradfield, C. (1996) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.93.13.6731 · Cited by 932 · see citing works
The Nuclear Pregnane X Receptor: A Key Regulator of Xenobiotic Metabolism
Kliewer, S. A., Goodwin, B. J., & Willson, T. M. (2002) · Endocrine Reviews · doi:10.1210/er.2001-0038 · Cited by 922 · see citing works
Waxman, D. J. (1999) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1999.1351 · Cited by 754 · see citing works
Aryl hydrocarbon receptors: diversity and evolution
Hahn, M. E. (2002) · Chemico-Biological Interactions · doi:10.1016/s0009-2797(02)00070-4 · Cited by 642 · see citing works
Benzo[ a ]pyrene carcinogenicity is lost in mice lacking the aryl hydrocarbon receptor
Shimizu, Y., Nakatsuru, Y., Ichinose, M., Takahashi, Y., Kume, H., Mimura, J., Fujii‐Kuriyama, Y., & Ishikawa, T. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.2.779 · Cited by 640 · see citing works
Self-citationMimura, J., Yamashita, K., Nakamura, K., Morita, M., Takagi, T. N., Nakao, K., Ema, M., Sogawa, K., Yasuda, M., Katsuki, M., et al. (1997) · Genes to Cells · doi:10.1046/j.1365-2443.1997.1490345.x · Cited by 626 · see citing works
Self-citationIdentification of a novel mechanism of regulation of Ah (dioxin) receptor functionPreprint
Mimura, J., Ema, M., Sogawa, K., & Fujii‐Kuriyama, Y. (1999) · Genes & Development · doi:10.1101/gad.13.1.20 · Cited by 584 · see citing works
Self-citationIndirubin and Indigo Are Potent Aryl Hydrocarbon Receptor Ligands Present in Human Urine
Adachi, J., Mori, Y., Matsui, S., Takigami, H., Fujino, J., Kitagawa, H., Miller, C. A., Kato, T., Saeki, K., & Matsuda, T. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.c100238200 · Cited by 407 · see citing works
Lahvis, G. P., Lindell, S. L., Thomas, R. S., McCuskey, R. S., Murphy, C., Glover, E., Bentz, M., Southard, J., & Bradfield, C. A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.190256997 · Cited by 377 · see citing works
Fujisawa‐Sehara, A., Sogawa, K., Yamane, M., & Fujii‐Kuriyama, Y. (1987) · Nucleic Acids Research · doi:10.1093/nar/15.10.4179 · Cited by 313 · see citing works
Self-citationA constitutively active dioxin/aryl hydrocarbon receptor induces stomach tumors
Andersson, P., McGuire, J., Rubio, C., Gradin, K., Whitelaw, M. L., Pettersson, S., Hanberg, A., & Poellinger, L. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.152706299 · Cited by 310 · see citing works
Anti-inflammatory actions of lipoxin A4 and aspirin-triggered lipoxin are SOCS-2 dependent
Machado, F. S., Johndrow, J. E., Esper, L., Dias, A., Báfica, A. L. B., Serhan, C. N., & Aliberti, J. (2006) · Nature Medicine · doi:10.1038/nm1355 · Cited by 309 · see citing works
Davarinos, N. A., & Pollenz, R. S. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.40.28708 · Cited by 306 · see citing works
Molecular mechanisms of AhR functions in the regulation of cytochrome P450 genes
Fujii-Kuriyama, Y., & Mimura, J. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.08.162 · Cited by 290 · see citing works
Self-citationNuclear Localization and Export Signals of the Human Aryl Hydrocarbon Receptor
Ikuta, T., Eguchi, H., Tachibana, T., Yoneda, Y., & Kawajiri, K. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.5.2895 · Cited by 287 · see citing works
Self-citationLipoxin A4: A New Class of Ligand for the Ah Receptor
Schaldach, C., Riby, J. E., & Bjeldanes, L. F. (1999) · Biochemistry · doi:10.1021/bi982861e · Cited by 265 · see citing works
Intrinsic Function of the Aryl Hydrocarbon (Dioxin) Receptor as a Key Factor in Female Reproduction
Baba, T., Mimura, J., Nakamura, N., Harada, N., Yamamoto, M., Morohashi, K.-I., & Fujii-Kuriyama, Y. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.22.10040-10051.2005 · Cited by 256 · see citing works
Self-citationA Constitutively Active Dioxin/Aryl Hydrocarbon Receptor Promotes Hepatocarcinogenesis in Mice
Moennikes, O., Loeppen, S., Buchmann, A., Andersson, P., Ittrich, C., Poellinger, L., & Schwarz, M. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-0875 · Cited by 228 · see citing works
Beischlag, T. V., Wang, S., Rose, D. W., Torchia, J., Reisz‐Porszasz, S., Muhammad, K., Nelson, W. E., Probst, M. R., Rosenfeld, M. G., & Hankinson, O. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.12.4319-4333.2002 · Cited by 223 · see citing works
Adverse Reproductive Outcomes in the Transgenic Ah Receptor-Deficient Mouse
Abbott, B. D., Schmid, J. E., Pitt, J. A., Buckalew, A. R., Wood, C. R., Held, G. A., & Diliberto, J. J. (1999) · Toxicology and Applied Pharmacology · doi:10.1006/taap.1998.8601 · Cited by 219 · see citing works
Funatake, C. J., Marshall, N. B., Steppan, L. B., Mourich, D. V., & Kerkvliet, N. I. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.7.4184 · Cited by 219 · see citing works
Bunger, M. K., Moran, S. M., Glover, E., Thomae, T. L., Lahvis, G. P., Lin, B. C., & Bradfield, C. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209594200 · Cited by 215 · see citing works
Walisser, J. A., Glover, E., Pande, K., Liss, A. L., & Bradfield, C. A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504757102 · Cited by 212 · see citing works
The hsp90 Chaperone Complex Regulates Intracellular Localization of the Dioxin Receptor
Kazlauskas, A., Sundström, S., Poellinger, L., & Pongratz, I. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.7.2594-2607.2001 · Cited by 211 · see citing works
Abbott, B. D., Birnbaum, L. S., & Perdew, G. H. (1995) · Developmental Dynamics · doi:10.1002/aja.1002040204 · Cited by 195 · see citing works
Aryl hydrocarbon receptor activation by cAMP vs. dioxin: Divergent signaling pathways
Oesch‐Bartlomowicz, B., Huelster, A., Wiss, O., Antoniou‐Lipfert, P., Dietrich, C., Arand, M., Weiß, C., Bockamp, E., & Oesch, F. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503488102 · Cited by 185 · see citing works
Abdelrahim, M., Smith, R., & Safe, S. H. (2003) · Molecular Pharmacology · doi:10.1124/mol.63.6.1373 · Cited by 167 · see citing works
Tauchi, M., Hida, A., Negishi, T., Katsuoka, F., Noda, S., Mimura, J., Hosoya, T., Yanaka, A., Aburatani, H., Fujii-Kuriyama, Y., et al. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.21.9360-9368.2005 · Cited by 167 · see citing works
Self-citationCooperative Interaction between AhR·Arnt and Sp1 for the Drug-inducible Expression of CYP1A1 Gene
Kobayashi, A., Sogawa, K., & Fujii‐Kuriyama, Y. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.21.12310 · Cited by 162 · see citing works
Self-citationWei, Y., Helleberg, H., Rannug, U., & Rannug, A. (1998) · Chemico-Biological Interactions · doi:10.1016/s0009-2797(97)00111-7 · Cited by 157 · see citing works
Swales, K. E., & Negishi, M. (2004) · Molecular Endocrinology · doi:10.1210/me.2003-0397 · Cited by 137 · see citing works
Roberts, B. J., & Whitelaw, M. L. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.51.36351 · Cited by 130 · see citing works
Cell Density Regulates Intracellular Localization of Aryl Hydrocarbon Receptor
Ikuta, T., Kobayashi, Y., & Kawajiri, K. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m310492200 · Cited by 125 · see citing works
Self-citationARA9 Modifies Agonist Signaling through an Increase in Cytosolic Aryl Hydrocarbon Receptor
LaPres, J. J., Glover, E., Dunham, E. E., Bunger, M. K., & Bradfield, C. A. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.9.6153 · Cited by 125 · see citing works
Kerkvliet, N. I. (2002) · Toxicology and Applied Pharmacology · doi:10.1006/taap.2002.9537 · Cited by 117 · see citing works
Regulation of aryl hydrocarbon receptor signal transduction by protein tyrosine kinases
Backlund, M., & Ingelman‐Sundberg, M. (2004) · Cellular Signalling · doi:10.1016/j.cellsig.2004.05.010 · Cited by 107 · see citing works
Wang, S., & Hankinson, O. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m110122200 · Cited by 107 · see citing works
Savas, Ü., Griffin, K. J., & Johnson, E. F. (1999) · Molecular Pharmacology · doi:10.1124/mol.56.5.851 · Cited by 107 · see citing works
A novel induction mechanism of the rat CYP1A2 gene mediated by Ah receptor–Arnt heterodimer
Sogawa, K., Numayama‐Tsuruta, K., Takahashi, T., Matsushita, N., Miura, C., Nikawa, J., Gotoh, O., Kikuchi, Y., & Fujii‐Kuriyama, Y. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.04.090 · Cited by 105 · see citing works
Self-citationMulero‐Navarro, S., Carvajal-González, J. M., Herranz, M., et al. (2006) · Carcinogenesis · doi:10.1093/carcin/bgi344 · Cited by 104 · see citing works
Ikuta, T., Kobayashi, Y., & Kawajiri, K. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.03.076 · Cited by 99 · see citing works
Self-citationNucleocytoplasmic Shuttling of the Aryl Hydrocarbon Receptor
Ikuta, T., Tachibana, T., Watanabe, J. A., Yoshida, M., Yoneda, Y., & Kawajiri, K. (2000) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a022633 · Cited by 90 · see citing works
Self-citationSadek, C. M., & Allen‐Hoffmann, B. L. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)31723-x · Cited by 89 · see citing works
Zinc finger transcription factor Slug is a novel target gene of aryl hydrocarbon receptor
Ikuta, T., & Kawajiri, K. (2006) · Experimental Cell Research · doi:10.1016/j.yexcr.2006.08.002 · Cited by 88 · see citing works
Self-citationEffects of Aryl Hydrocarbon Receptor Signaling on the Modulation of Th1/Th2 Balance1
Negishi, T., Kato, Y., Ooneda, O., Mimura, J., Takada, T., Mochizuki, H., Yamamoto, M., Fujii-Kuriyama, Y., & Furusako, S. (2005) · Journal of Immunology · doi:10.4049/jimmunol.175.11.7348 · Cited by 85 · see citing works
Self-citationRegulation of Dioxin Receptor Function by Omeprazole
Dzeletovic, N., McGuire, J., Daujat‐Chavanieu, M., Tholander, J., Ema, M., Fujii‐Kuriyama, Y., Bergman, J., Maurel, P., & Poellinger, L. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.19.12705 · Cited by 85 · see citing works
Self-citationRole of Mediator in Transcriptional Activation by the Aryl Hydrocarbon Receptor
Wang, S., Ge, K., Roeder, R. G., & Hankinson, O. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312274200 · Cited by 84 · see citing works
Nohara, K., Pan, X.-Q., Tsukumo, S., Hida, A., Ito, T., Nagai, H., Inouye, K., Motohashi, H., Yamamoto, M., Fujii-Kuriyama, Y., et al. (2005) · Journal of Immunology · doi:10.4049/jimmunol.174.5.2770 · Cited by 67 · see citing works
Self-citationCho, Y. C., Zheng, W., & Jefcoate, C. (2004) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2003.12.025 · Cited by 66 · see citing works
Loss of heterozygosity for the short arm of chromosome 7 in sporadic Wilms tumour
Grundy, R. G., Pritchard, J., Scambler, P. J., et al. (1998) · Oncogene · doi:10.1038/sj.onc.1201927 · Cited by 45 · see citing works
Berg, P., & Pongratz, I. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105261200 · Cited by 43 · see citing works
Falahatpisheh, M. H., & Ramos, K. S. (2003) · Oncogene · doi:10.1038/sj.onc.1206238 · Cited by 41 · see citing works
Ikuta, T., Watanabe, J. A., & Kawajiri, K. (2002) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a003080 · Cited by 24 · see citing works
Self-citationMolecular characterization of a 7p15–21 homozygous deletion in a Wilms tumor
Sossey‐Alaoui, K., Vieira, L., David, D., et al. (2002) · Genes Chromosomes and Cancer · doi:10.1002/gcc.10133 · Cited by 14 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Cytochrome P450 Enzymes and Drug Metabolism in Humans
Zhao, M., Ma, J., Li, M., Zhang, Y., Jiang, B., Zhao, X., Huai, C., Shen, L., Zhang, N., He, L., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222312808 · Cited by 1,070 · see citing works
Joubert, B. R., Håberg, S. E., Nilsen, R. M., Wang, X., Vollset, S. E., Murphy, S. K., Huang, Z., Hoyo, C., Midttun, Ø., Cupul-Uicab, L. A., et al. (2012) · Environmental Health Perspectives · doi:10.1289/ehp.1205412 · Cited by 716 · see citing works
Pan, C., Kumar, C., Bohl, S., Klingmueller, U., & Mann, M. (2009) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m800258-mcp200 · Cited by 561 · see citing works
“Two of them (CYP1A1 and CYP2S1) are known to be regulated by the aryl hydrogen receptor ( 25 , 26).”
BackgroundKajta, M., & Wójtowicz, A. K. (2013) · Pharmacological Reports · doi:10.1016/s1734-1140(13)71524-x · Cited by 168 · see citing works
Sun, Y. V. (2014) · Current Genetic Medicine Reports · doi:10.1007/s40142-014-0058-2 · Cited by 27 · see citing works
- Authors
- Kawajiri, K., & Fujii-Kuriyama, Y.
- Affiliations
- Research Institute for Clinical Oncology, Saitama Cancer Center (JP)
- Venue
- Archives of Biochemistry and Biophysics
- Publisher
- Elsevier BV
- Published
- 2007-08
- Volume
- 464
- Issue
- 2
- Pages
- 207-212
- ISSN
- 0003-9861 (ISSN-L)
- OpenAlex
- W2071960770
- Cited by
- 197
- References
- 57
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 5 · 2022: 4 · 2021: 10 · 2020: 7 · 2019: 3 · 2018: 13 · 2017: 6 · 2016: 14 · 2015: 11 · 2014: 12 · 2013: 16 · 2012: 13
- FWCI
- 2.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Biochemistry and Biophysics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Keywords
- aryl hydrocarbon receptor, cytochrome P450, CYP1A1 induction, gene expression regulation, transcription factors, physiological function, developmental homeostasis
- MeSH terms
- Cytochrome P-450 Enzyme System, Models, Biological, Signal Transduction, Gene Expression Regulation, Enzymologic, Receptors, Aryl Hydrocarbon
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
