scholarly journals Aryl hydrocarbon receptor (AHR): “pioneer member” of the basic-helix/loop/helix per - Arnt - sim (bHLH/PAS) family of “sensors” of foreign and endogenous signals

2017 ◽  
Vol 67 ◽  
pp. 38-57 ◽  
Author(s):  
Daniel W. Nebert
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Aryl Hydrocarbon

scholarly journals cDNA cloning and tissue-specific expression of a novel basic helix-loop-helix/PAS factor (Arnt2) with close sequence similarity to the aryl hydrocarbon receptor nuclear translocator (Arnt).

1996 ◽  
Vol 16 (4) ◽  
pp. 1706-1713 ◽  
Author(s):  
K Hirose ◽  
M Morita ◽  
M Ema ◽  
J Mimura ◽  
H Hamada ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Sequence Similarity ◽  
Cdna Clones ◽  
Mobility Shift ◽  
Phylogenetic Groups ◽  
Specific Expression ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Aryl Hydrocarbon ◽  
Adult Mice

We isolated mouse cDNA clones (Arnt2) that are highly similar to but distinct from the aryl hydrocarbon receptor (AhR) nuclear translocator (Arnt). The composite cDNA covered a 2,443-bp sequence consisting of a putative 2,136-bp open reading frame encoding a polypeptide of 712 amino acids. The predicted Arnt2 polypeptide carries a characteristic basic helix-loop-helix (bHLH)/PAS motif in its N-terminal region with close similarity (81% identity) to that of mouse Arnt and has an overall sequence identity of 57% with Arnt. Biochemical properties and interaction of Arnt2 with other bHLH/PAS proteins were investigated by coimmunoprecipitation assays, gel mobility shift assays, and the yeast two-hybrid system. Arnt2 interacted with AhR and mouse Sim as efficiently as Arnt, and the Arnt2-AhR complex recognized and bound specifically the xenobiotic responsive element (XRE) sequence. Expression of Arnt2 successfully rescued XRE-driven reporter gene activity in the Arnt-defective c4 mutant of Hepa-1 cells. RNA blot analysis revealed that expression of Arnt2 mRNA was restricted to the brains and kidneys of adult mice, while Arnt mRNA was expressed ubiquitously. In addition, whole-mount in situ hybridization of 9.5-day mouse embryos showed that Arnt2 mRNA was expressed in the dorsal neural tube and branchial arch 1, while Arnt transcripts were detected broadly in various tissues of mesodermal and endodermal origins. These results suggest that Arnt2 may play different roles from Arnt both in adult mice and in developing embryos. Finally, sequence comparison of the currently known bHLH/PAS proteins indicates a division into two phylogenetic groups: the Arnt group, containing Arnt, Arnt2, and Per, and the AhR group, consisting of AhR, Sim, and Hif-1alpha.

scholarly journals 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 ◽  
2000 ◽  
Vol 141 (1) ◽  
pp. 450-453 ◽  
Author(s):  
Rodolfo Robles ◽  
Yutaka Morita ◽  
Koren K. Mann ◽  
Gloria I. Perez ◽  
Shi Yang ◽  
...  
Keyword(s):  
Cell Death ◽  
Transcription Factors ◽  
Germ Cell ◽  
Aryl Hydrocarbon Receptor ◽  
Germ Line ◽  
Wild Type ◽  
Cell Dynamics ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Aryl Hydrocarbon

Abstract The aryl hydrocarbon receptor (AhR), so-designated based on the ability of the protein to bind with and be activated by polycyclic aromatic hydrocarbons (PAH) and related halogenated hydrocarbons, is part of an emerging family of ligand-activated transcriptional regulators that are distinct from the steroid-thyroid hormone receptor superfamily. Once bound by ligand, the AhR interacts with the AhR nuclear translocator (ARNT) protein to form the aryl hydrocarbon receptor complex (AHRC). Both subunits of the AHRC contain sequences corresponding to basic helix-loop-helix domains, a motif that is shared by a number of other dimeric transcription factors. Although the natural ligand(s) for the AhR remains to be elucidated, to date over fifteen genes, including enzymes, growth factors and other transcription factors, have been identified as potential targets for transcriptional regulation by the chemically-activated AHRC. In the ovary, PAH exposure is known to cause destruction of oocytes within immature follicles, implying that one function of the AhR is to mediate cell death signaling in the female germ line. To assess this possibility, we explored AhR expression patterns in the murine ovary, and then determined the impact of AhR-deficiency (gene knockout) on female germ cell dynamics. Immunohistochemical analysis of ovaries of wild-type female mice indicated that AhR protein was abundantly and exclusively expressed in oocytes and granulosa cells of follicles at all stages of development. Histomorphometric analysis of serial ovarian sections revealed a two-fold higher number of primordial follicles in Ahr-null versus wild-type females at day 4 postpartum. This phenotype likely results from a cell-intrinsic death defect in the developing germ line since AhR-deficiency attenuated the magnitude of oocyte apoptosis in fetal ovaries cultured without hormonal support for 72 h. We propose that the AhR, activated by an as yet unknown endogenous ligand(s), serves to regulate the size of the oocyte reserve endowed at birth by affecting germ cell death during female gametogenesis.

scholarly journals Antioxidant Functions of the Aryl Hydrocarbon Receptor

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Cornelia Dietrich
Keyword(s):  
Polycyclic Aromatic Hydrocarbons ◽  
Aryl Hydrocarbon Receptor ◽  
Aromatic Hydrocarbons ◽  
Transcriptional Activation ◽  
Antioxidant Response ◽  
Protective Role ◽  
Helix Loop Helix ◽  
Aryl Hydrocarbon ◽  
Polycyclic Aromatic

The aryl hydrocarbon receptor (AhR) is a transcription factor belonging to the basic helix-loop-helix/PER-ARNT-SIM family. It is activated by a variety of ligands, such as environmental contaminants like polycyclic aromatic hydrocarbons or dioxins, but also by naturally occurring compounds and endogenous ligands. Binding of the ligand leads to dimerization of the AhR with aryl hydrocarbon receptor nuclear translocator (ARNT) and transcriptional activation of several xenobiotic phase I and phase II metabolizing enzymes. It is generally accepted that the toxic responses of polycyclic aromatic hydrocarbons, dioxins, and structurally related compounds are mediated by activation of the AhR. A multitude of studies indicate that the AhR operates beyond xenobiotic metabolism and exerts pleiotropic functions. Increasing evidence points to a protective role of the AhR against carcinogenesis and oxidative stress. Herein, I will highlight data demonstrating a causal role of the AhR in the antioxidant response and present novel findings on potential AhR-mediated antioxidative mechanisms.

Molecular characteristics and induction profiles of hypoxia-inducible factor-1αand other basic helix–loop–helix and Per–Arnt–Sim domain-containing proteins identified in a carcinogenic liver flukeClonorchis sinensis

Parasitology ◽  
2018 ◽  
Vol 146 (2) ◽  
pp. 176-186
Author(s):  
Seon-Hee Kim ◽  
Gyu-Seok Oh ◽  
Woon-Mok Sohn ◽  
Kihyun Lee ◽  
Hyun-Jong Yang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Clonorchis Sinensis ◽  
Hypoxia Inducible Factor ◽  
Hypoxic Condition ◽  
Molecular Structures ◽  
Molecular Characteristics ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Aryl Hydrocarbon ◽  
Oxygen Condition

AbstractClonorchis sinensis(C. sinensis), a trematode parasite that invades the hypoxic hepatobiliary tract of vertebrate hosts requires a considerable amount of oxygen for its sexual reproduction and energy metabolism. However, little is known regarding the molecular mechanism ofC. sinensisinvolved in the adaptation to the hypoxic environments. In this study, we investigated the molecular structures and induction patterns of hypoxia-inducible factor-1α(HIF-1α) and other basic helix–loop–helix and Per–Arnt–Sim (bHLH–PAS) domain-containing proteins such as HIF-1β, single-minded protein and aryl hydrocarbon receptor, which might prompt adaptive response to hypoxia, inC. sinensis. These proteins possessed various bHLH–PAS family-specific domains. Expression ofC. sinensis HIF-1α(CsHIF-1α) was highly induced in worms which were either exposed to a hypoxic condition or co-incubated with human cholangiocytes. In addition to oxygen, nitric oxide and nitrite affected theCsHIF-1αexpression depending on the surrounding oxygen concentration. Treatment using a prolyl hydroxylase-domain protein inhibitor under 20%-oxygen condition resulted in an increase in the CsHIF-1αlevel. Conversely, the otherbHLH–PASgenes were less responsive to these exogenous stimuli. We suggest that nitrite and nitric oxide, as well as oxygen, coordinately involve in the regulation of HIF-1αexpression to adapt to the hypoxic host environments inC. sinensis.

Identification of functional domains of the aryl hydrocarbon receptor nuclear translocator protein (ARNT)

1994 ◽  
Vol 14 (9) ◽  
pp. 6075-6086
Author(s):  
S Reisz-Porszasz ◽  
M R Probst ◽  
B N Fukunaga ◽  
O Hankinson
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Mutant Cell ◽  
Translocator Protein ◽  
Functional Domains ◽  
Recognition Sequence ◽  
Dimerization Domain ◽  
Alpha Helices ◽  
Helix Loop Helix ◽  
Aryl Hydrocarbon

The activated aryl hydrocarbon receptor (AHR) and the AHR nuclear translocator (ARNT) bind DNA as a heterodimer. Both proteins represent a novel class of basic helix-loop-helix (bHLH)-containing transcription factors in that (i) activation of AHR requires the binding of ligand (e.g., 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD]), (ii) the xenobiotic responsive element (XRE) recognized by the AHR/ARNT heterodimer differs from the recognition sequence for nearly all other bHLH proteins, and (iii) both proteins contain a PAS homology region, which in the Drosophila PER and SIM proteins functions as a dimerization domain. A cDNA for mouse ARNT has been cloned, and potential functional domains of ARNT were investigated by deletion analysis. A mutant lacking all regions of ARNT other than the bHLH and PAS regions is unimpaired in TCDD-dependent dimerization and subsequent XRE binding and only modestly reduced in ability to complement an ARNT-deficient mutant cell line, c4, in vivo. Both the first and second alpha helices of the bHLH region are required for dimerization. The basic region is required for XRE binding but not for dimerization. Deletion of either the A or B segments of the PAS region slightly affects TCDD-induced heterodimerization, while deletion of the complete PAS region severely affects (but does not eliminate) dimerization. Thus, ARNT possesses multiple domains required for maximal heterodimerization. Mutants deleted for PAS A, PAS B, and the complete PAS region all retain some degree of XRE binding, yet none can rescue the c4 mutant. Therefore, both the PAS A and PAS B segments, besides contributing to dimerization, apparently fulfill additional, unknown functions required for biological activity of ARNT.

scholarly journals Identification of functional domains of the aryl hydrocarbon receptor nuclear translocator protein (ARNT).

1994 ◽  
Vol 14 (9) ◽  
pp. 6075-6086 ◽  
Author(s):  
S Reisz-Porszasz ◽  
M R Probst ◽  
B N Fukunaga ◽  
O Hankinson
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Mutant Cell ◽  
Translocator Protein ◽  
Functional Domains ◽  
Recognition Sequence ◽  
Dimerization Domain ◽  
Alpha Helices ◽  
Helix Loop Helix ◽  
Aryl Hydrocarbon

The activated aryl hydrocarbon receptor (AHR) and the AHR nuclear translocator (ARNT) bind DNA as a heterodimer. Both proteins represent a novel class of basic helix-loop-helix (bHLH)-containing transcription factors in that (i) activation of AHR requires the binding of ligand (e.g., 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD]), (ii) the xenobiotic responsive element (XRE) recognized by the AHR/ARNT heterodimer differs from the recognition sequence for nearly all other bHLH proteins, and (iii) both proteins contain a PAS homology region, which in the Drosophila PER and SIM proteins functions as a dimerization domain. A cDNA for mouse ARNT has been cloned, and potential functional domains of ARNT were investigated by deletion analysis. A mutant lacking all regions of ARNT other than the bHLH and PAS regions is unimpaired in TCDD-dependent dimerization and subsequent XRE binding and only modestly reduced in ability to complement an ARNT-deficient mutant cell line, c4, in vivo. Both the first and second alpha helices of the bHLH region are required for dimerization. The basic region is required for XRE binding but not for dimerization. Deletion of either the A or B segments of the PAS region slightly affects TCDD-induced heterodimerization, while deletion of the complete PAS region severely affects (but does not eliminate) dimerization. Thus, ARNT possesses multiple domains required for maximal heterodimerization. Mutants deleted for PAS A, PAS B, and the complete PAS region all retain some degree of XRE binding, yet none can rescue the c4 mutant. Therefore, both the PAS A and PAS B segments, besides contributing to dimerization, apparently fulfill additional, unknown functions required for biological activity of ARNT.

scholarly journals Diet–Host–Microbiota Interactions Shape Aryl Hydrocarbon Receptor Ligand Production to Modulate Intestinal Homeostasis

2021 ◽  
Vol 41 (1) ◽  
pp. 455-478
Author(s):  
Huajun Han ◽  
Stephen Safe ◽  
Arul Jayaraman ◽  
Robert S. Chapkin
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Environmental Toxicants ◽  
Cellular Functions ◽  
Developmental Defects ◽  
Helix Loop Helix ◽  
Aryl Hydrocarbon ◽  
Colon Tumorigenesis ◽  
Wide Range ◽  
Bowel Diseases ◽  
Context Specific

The aryl hydrocarbon receptor (AhR) is a ligand-activated basic-helix-loop-helix transcription factor that binds structurally diverse ligands and senses cues from environmental toxicants and physiologically relevant dietary/microbiota-derived ligands. The AhR is an ancient conserved protein and is widely expressed across different tissues in vertebrates and invertebrates. AhR signaling mediates a wide range of cellular functions in a ligand-, cell type–, species-, and context-specific manner. Dysregulation of AhR signaling is linked to many developmental defects and chronic diseases. In this review, we discuss the emerging role of AhR signaling in mediating bidirectional host–microbiome interactions. We also consider evidence showing the potential for the dietary/microbial enhancement ofhealth-promoting AhR ligands to improve clinical pathway management in the context of inflammatory bowel diseases and colon tumorigenesis.

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