Ah receptor pathway intricacies; signaling through diverse protein partners and DNA-motifs

Jackson, D. Paul; Joshi, Atul; Elferink, Cornelis

doi:10.1039/c4tx00236a

Cited by 53 publications

(44 citation statements)

References 268 publications

(583 reference statements)

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“…The AHR is thus an integral component of the mechanism by which DLCs and some PAHs cause toxicity, and loss of AHR function protects against these effects (Fernandez‐Salguero et al., 1996; Goodale et al., 2012; Mimura et al., 1997; Prasch et al., 2003). Although the AHR is now known to participate in a variety of additional, noncanonical interactions and pathways (Jackson, Joshi, & Elferink, 2015), the primary mechanism of toxicity appears to involve canonical interactions requiring nuclear localization, dimerization with ARNT, and binding to AHREs (Bunger et al., 2003, 2008; Nukaya, Walisser, Moran, Kennedy, & Bradfield, 2010; Walisser, Bunger, Glover, Harstad, & Bradfield, 2004). …”

Section: Ahr Pathwaymentioning

confidence: 99%

When evolution is the solution to pollution: Key principles, and lessons from rapid repeated adaptation of killifish (Fundulus heteroclitus) populations

Whitehead

Clark

Reid

et al. 2017

Evolutionary Applications

120

102

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For most species, evolutionary adaptation is not expected to be sufficiently rapid to buffer the effects of human‐mediated environmental changes, including environmental pollution. Here we review how key features of populations, the characteristics of environmental pollution, and the genetic architecture underlying adaptive traits, may interact to shape the likelihood of evolutionary rescue from pollution. Large populations of Atlantic killifish (Fundulus heteroclitus) persist in some of the most contaminated estuaries of the United States, and killifish studies have provided some of the first insights into the types of genomic changes that enable rapid evolutionary rescue from complexly degraded environments. We describe how selection by industrial pollutants and other stressors has acted on multiple populations of killifish and posit that extreme nucleotide diversity uniquely positions this species for successful evolutionary adaptation. Mechanistic studies have identified some of the genetic underpinnings of adaptation to a well‐studied class of toxic pollutants; however, multiple genetic regions under selection in wild populations seem to reflect more complex responses to diverse native stressors and/or compensatory responses to primary adaptation. The discovery of these pollution‐adapted killifish populations suggests that the evolutionary influence of anthropogenic stressors as selective agents occurs widely. Yet adaptation to chemical pollution in terrestrial and aquatic vertebrate wildlife may rarely be a successful “solution to pollution” because potentially adaptive phenotypes may be complex and incur fitness costs, and therefore be unlikely to evolve quickly enough, especially in species with small population sizes.

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Section: Ahr Pathwaymentioning

confidence: 99%

When evolution is the solution to pollution: Key principles, and lessons from rapid repeated adaptation of killifish (Fundulus heteroclitus) populations

Whitehead

Clark

Reid

et al. 2017

Evolutionary Applications

120

102

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show abstract

“…AhR-dependent alterations in the expression of genes that lack an apparent AhR DNA (DRE) binding site, coupled with established cross-talk between the AhR and cellular signaling pathways and other transcription factors, suggests that the AhR participates in several novel noncannonical pathways by which the AhR can stimulate gene expression [6,20–23]. Ligand-activated AhR can dimerize with nuclear proteins other than ARNT (e.g., Kruppel-like factor 6 (KLF6) and RelB), and these unique heterodimers stimulate gene expression via their interaction with DNA binding sites that are significantly different from that of a DRE [24–28] to regulate a unique set of genes (Figure 1). While little is known about the specific protein:protein interactions that occur between the AhR and RelB [24], deletion and functional analysis studies revealed that the mode of AhR:KLF6 dimerization is distinctly different from that of the AhR:ARNT dimer [27].…”

Section: Diversity In Ahr-dependent Mechanisms Of Gene Expressionmentioning

confidence: 99%

And now for something completely different: Diversity in ligand-dependent activation of Ah receptor responses

Denison

Faber

2017

Current Opinion in Toxicology

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Ligand-dependent activation of the Ah receptor (AhR) can result in an extremely diverse spectrum of biological and toxic effects that occur in a ligand-, species- and tissue-specific manner. While the classical mechanism of AhR-dependent signal transduction is directly related to its ability to modulate gene expression, the dramatic diversity in responses observed following AhR activation or inhibition is inconsistent with a single molecular mechanism of AhR action. Recent studies have revealed that key molecular events underlying the AhR signaling pathway are significantly more varied and complex than previously established, and the specificity and diversity in AhR response can be selectively modulated by a variety of factors. Here we describe new insights into the mechanistic diversity in AhR signal transduction that can contribute to ligand-, species- and tissue-specific differences in AhR reponse.

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“…Its overexpression in transgenic mice suppresses the mCYP1A1 induction in lung, spleen, and adipose tissue [45]. Moreover, it has been suggested that rat CYP1A1 regulates its own expression because it catalyzes the removal of AHR agonists and thus decreases the activation of this pathway [46, 47]. …”

Section: Downregulation Of Cyp1a1mentioning

confidence: 99%

Regulation of Human Cytochrome P4501A1 (hCYP1A1): A Plausible Target for Chemoprevention?

Santes-Palacios¹,

Ornelas-Ayala²,

Cabañas³

et al. 2016

BioMed Research International

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Human cytochrome P450 1A1 (hCYP1A1) has been an object of study due to its role in precarcinogen metabolism; for this reason it is relevant to know more in depth the mechanisms that rule out its expression and activity, which make this enzyme a target for the development of novel chemiopreventive agents. The aim of this work is to review the origin, regulation, and structural and functional characteristics of CYP1A1 letting us understand its role in the bioactivation of precarcinogen and the consequences of its modulation in other physiological processes, as well as guide us in the study of this important protein.

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Ah receptor pathway intricacies; signaling through diverse protein partners and DNA-motifs

Abstract: The Ah receptor is a transcription factor that modulates gene expression via interactions with multiple protein partners; these are reviewed, including the novel NC-XRE pathway involving KLF6.

Cited by 53 publications

References 268 publications

When evolution is the solution to pollution: Key principles, and lessons from rapid repeated adaptation of killifish (Fundulus heteroclitus) populations

When evolution is the solution to pollution: Key principles, and lessons from rapid repeated adaptation of killifish (Fundulus heteroclitus) populations

And now for something completely different: Diversity in ligand-dependent activation of Ah receptor responses

Regulation of Human Cytochrome P4501A1 (hCYP1A1): A Plausible Target for Chemoprevention?

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