The Aryl Hydrocarbon Receptor-interacting Protein (AIP) Is Required for Dioxin-induced Hepatotoxicity but Not for the Induction of the Cyp1a1 and Cyp1a2 Genes

Nukaya, Manabu; Lin, Bernice C.; Glover, Edward; Moran, Susan M.; Kennedy, Gregory D.; Bradfield, Christopher A.

doi:10.1074/jbc.m110.132043

Cited by 50 publications

(56 citation statements)

References 36 publications

(56 reference statements)

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“…There are several other “control points” in the AHR signaling cascade that can influence the sensitivity to or magnitude of response (Beischlag, Luis Morales, Hollingshead, & Perdew, 2008; Hahn, 1998b). Similarly, the AHR is not the only factor that influences sensitivity to effects of DLCs; the expression and function of other members of the AHR pathway, including ARNT (Nukaya, Walisser, et al., 2010; Tomita, Sinal, Yim, & Gonzalez, 2000; Walisser et al., 2004) and AIP (Nukaya, Lin, et al., 2010), also are important. In addition, the expression and inducibility of biotransformation enzymes can influence sensitivity, especially for labile AHR ligands such as PAHs (Billiard et al., 2008; Brown, Clark, Garner, & Di Giulio, 2015).…”

Section: Ahr Pathwaymentioning

confidence: 99%

“…For example, the most significant QTL identified, explaining up to 46% of the phenotypic variance within families analyzed (Nacci, Proestou, et al., 2016), was nearby to the gene encoding aryl hydrocarbon receptor interacting protein ( AIP , also known as HBV x‐associated protein 2 , XAP2 , and AH receptor‐activated 9 , ARA9 ; Trivellin & Korbonits, 2011) (Figure 4). While the roles of AIP are not precisely known and may vary by species and life stage, it is known to modulate the function of AHR signaling (Petrulis, Kusnadi, Ramadoss, Hollingshead, & Perdew, 2003), and influences DLC toxicity (Nukaya, Lin, et al., 2010). Another genetic marker near AIP interacted significantly as an additive QTL with HSP90 .…”

Section: Genetic Basis Of Pollution Tolerance In Killifishmentioning

confidence: 99%

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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

118

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%

Section: Genetic Basis Of Pollution Tolerance In Killifishmentioning

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

118

102

View full text Add to dashboard Cite

show abstract

“…In addition to its role as a cochaperone stabilizing the aryl hydrocarbon receptor (32,33) in the xenobiotic response to polycyclic aromatic compounds, for instance, 2,3,7,8-tetrachlorodibenzo-p-dioxin or "dioxin" (34), AIP has recently attracted attention for its potential link to certain types of pituitary adenomas (35). Accordingly, ϳ15% of patients with a rare neuroendocrine syndrome called familial isolated pituitary adenoma, but not sporadic adenomas (36), have been shown to harbor a variety of defects in the AIP locus (37), including inactivating germ line mutations as well as large genomic deletions (38) that disrupt the COOH-terminal of the AIP protein.…”

Section: Discussionmentioning

confidence: 99%

Developmental Control of Apoptosis by the Immunophilin Aryl Hydrocarbon Receptor-interacting Protein (AIP) Involves Mitochondrial Import of the Survivin Protein

Kang

Xia

Pop

et al. 2011

Journal of Biological Chemistry

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Survivin is a multifunctional protein with essential roles in cell division and inhibition of apoptosis, but the molecular underpinnings of its cytoprotective properties are poorly understood. Here we show that homozygous deletion of the aryl hydrocarbon receptor-interacting protein (AIP), a survivin-associated immunophilin, causes embryonic lethality in mice by embryonic day 13.5-14, increased apoptosis of Ter119 ؊ / CD71؊ early erythropoietic progenitors, and loss of survivin expression in its cytosolic and mitochondrial compartments in vivo. In import assays using recombinant proteins, AIP directly mediated the import of survivin to mitochondria, thus enabling its anti-apoptotic function, whereas a survivin 1-141 mutant that does not bind AIP was not imported to mitochondria and failed to inhibit apoptosis. AIP-directed mitochondrial import of survivin did not affect cell division, was independent of the organelle transmembrane potential, did not require the chaperone Heat Shock Protein 90 (Hsp90), and was inhibited by cytosolic factor(s) present in normal cells. shRNA knockdown of the mitochondrial import receptor Tom20 abolished mitochondrial import of survivin and sensitized tumor cells to apoptosis, whereas silencing of Tom70 had no effect. Therefore, an AIPTom20 recognition contributes to cell survival in development and cancer by mediating the mitochondrial import of survivin.

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“…Some studies reported that AIP can enhance the transcriptional activity and expression levels of the AhR (Carver & Bradfield 1997, Ma & Whitlock 1997, Meyer et al 1998, LaPres et al 2000, Nukaya et al 2010, whereas others described an inhibitory function , Pollenz & Dougherty 2005, Pollenz et al 2006. This variability is due to several factors, including species-and tissue-specific differences.…”

Section: Ppiase-likementioning

confidence: 99%

AIP and its interacting partners

Trivellin¹,

Korbonits²

2011

Journal of Endocrinology

129

119

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Germline mutations in the aryl hydrocarbon receptorinteracting protein gene (AIP) predispose to young-onset pituitary tumours, most often to GH-or prolactin-secreting adenomas, and most of these patients belong to familial isolated pituitary adenoma families. The molecular pathway initiated by the loss-of-function AIP mutations leading to pituitary tumour formation is unknown. AIP, a co-chaperone of heat-shock protein 90 and various nuclear receptors, belongs to the family of tetratricopeptide repeat (TPR)-containing proteins. It has three antiparallel a-helix motifs (TPR domains) that mediate the interaction of AIP with most of its partners. In this review, we summarise the known interactions of AIP described so far. The identification of AIP partners and the understanding of how AIP interacts with these proteins might help to explain the specific phenotype of the families with heterozygous AIP mutations, to gain deeper insight into the pathological process of pituitary tumour formation and to identify novel drug targets.

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The Aryl Hydrocarbon Receptor-interacting Protein (AIP) Is Required for Dioxin-induced Hepatotoxicity but Not for the Induction of the Cyp1a1 and Cyp1a2 Genes

Cited by 50 publications

References 36 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

Developmental Control of Apoptosis by the Immunophilin Aryl Hydrocarbon Receptor-interacting Protein (AIP) Involves Mitochondrial Import of the Survivin Protein

AIP and its interacting partners

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