| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print December 12, 2001
Department of Biology, Woods Hole Oceanographic Institution, Woods Hole, MA 02543
Corresponding Author: mhahn{at}whoi.edu
The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds occur via the aryl hydrocarbon receptor (AHR), a member of the bHLH-PAS protein superfamily. A single AHR gene has been identified in mammals, while many fish species, including the Atlantic killifish (Fundulus heteroclitus) possess two distinct AHR genes (AHR1 and a novel form, AHR2). A mouse bHLH-PAS protein closely related to AHR and designated AHR repressor (AHRR) is induced by 3-methylcholanthrene and represses the transcriptional activity of the AHR. To determine whether AHRR is the mammalian ortholog of fish AHR2 and to investigate the mechanisms by which AHRR regulates AHR function, we cloned an AHRR ortholog in F. heteroclitus with high sequence identity to the mouse and human AHRRs. Killifish AHRR encodes a 680 residue protein with a predicted molecular mass of 75.2 kDa. We show that in vitro-expressed AHRR proteins from human, mouse, and killifish all fail to bind [3H]TCDD or [3H]b-naphthoflavone. In transient transfection experiments using a luciferase reporter gene under control of AHR response elements, killifish AHRR inhibited the TCDD-dependent transactivation function of both AHR1 and AHR2. AHRR mRNA is widely expressed in killifish tissues and is inducible by TCDD or polychlorinated biphenyls, but its expression is not altered in a population of fish exhibiting genetic resistance to these compounds. The F. heteroclitus AHRR promoter contains three putative AHR response elements. Both AHR1 and AHR2 activated transcription of luciferase driven by the AHRR promoter, and AHRR could repress its own promoter. Thus, AHRR is an evolutionarily conserved, TCDD-inducible repressor of AHR1 and AHR2 function. Phylogenetic analysis shows that AHRR, AHR1, and AHR2 are distinct genes, members of an AHR gene family; these three vertebrate AHR-like genes descended from a single invertebrate AHR.
J. Biol. Chem, 10.1074/jbc.M110779200
Submitted on November 9, 2001
Revised on December 3, 2001
Accepted on December 12, 2001
Regulatory interactions among three members of the vertebrate aryl hydrocarbon receptor family: AHR repressor, AHR1, and AHR2
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  S. M. Billiard, J. N. Meyer, D. M. Wassenberg, P. V. Hodson, and R. T. Di Giulio Nonadditive effects of PAHs on Early Vertebrate Development: mechanisms and implications for risk assessment Toxicol. Sci., September 1, 2008; 105(1): 5 - 23. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Zimmermann, E. A. King, E. Dengler, S. R. Scogin, and W. H. Powell An Aryl Hydrocarbon Receptor Repressor from Xenopus laevis: Function, Expression, and Role in Dioxin Responsiveness during Frog Development Toxicol. Sci., July 1, 2008; 104(1): 124 - 134. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. R. Evans, S. I. Karchner, L. L. Allan, R. S. Pollenz, R. L. Tanguay, M. J. Jenny, D. H. Sherr, and M. E. Hahn Repression of Aryl Hydrocarbon Receptor (AHR) Signaling by AHR Repressor: Role of DNA Binding and Competition for AHR Nuclear Translocator Mol. Pharmacol., February 1, 2008; 73(2): 387 - 398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yasui, E.-Y. Kim, H. Iwata, D. G. Franks, S. I. Karchner, M. E. Hahn, and S. Tanabe Functional Characterization and Evolutionary History of Two Aryl Hydrocarbon Receptor Isoforms (AhR1 and AhR2) from Avian Species Toxicol. Sci., September 1, 2007; 99(1): 101 - 117. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Wang, B. E. Scheffler, and K. L. Willett CYP1C1 Messenger RNA Expression is Inducible by Benzo[a]pyrene in Fundulus heteroclitus Embryos and Adults Toxicol. Sci., October 1, 2006; 93(2): 331 - 340. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. I. Karchner, D. G. Franks, S. W. Kennedy, and M. E. Hahn The molecular basis for differential dioxin sensitivity in birds: Role of the aryl hydrocarbon receptor PNAS, April 18, 2006; 103(16): 6252 - 6257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Volz, D. E. Hinton, J. M. Law, and S. W. Kullman Dynamic Gene Expression Changes Precede Dioxin-Induced Liver Pathogenesis in Medaka Fish Toxicol. Sci., February 1, 2006; 89(2): 524 - 534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Lavine, A. J. Rowatt, T. Klimova, A. J. Whitington, E. Dengler, C. Beck, and W. H. Powell Aryl Hydrocarbon Receptors in the Frog Xenopus laevis: Two AhR1 Paralogs Exhibit Low Affinity for 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) Toxicol. Sci., November 1, 2005; 88(1): 60 - 72. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Tsuchiya, M. Nakajima, S. Itoh, M. Iwanari, and T. Yokoi Expression of Aryl Hydrocarbon Receptor Repressor in Normal Human Tissues and Inducibility by Polycyclic Aromatic Hydrocarbons in Human Tumor-Derived Cell Lines Toxicol. Sci., April 1, 2003; 72(2): 253 - 259. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. Meyer, D. E. Nacci, and R. T. Di Giulio Cytochrome P4501A (CYP1A) in Killifish (Fundulus heteroclitus): Heritability of Altered Expression and Relationship to Survival in Contaminated Sediments Toxicol. Sci., July 1, 2002; 68(1): 69 - 81. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
