CBP/p300 Functions as a Possible Transcriptional Coactivator of Ah Receptor Nuclear Translocator (Arnt)

Kobayashi, Akira; Numayama-Tsuruta, Keiko; Sogawa, Kazuhiro; Fujii‐Kuriyama, Yoshiaki

doi:10.1093/oxfordjournals.jbchem.a021812

Cited by 164 publications

(114 citation statements)

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“…Although it is unclear how this inhibition occurs, a potential mechanism may be through competition for coactivator/corepressor proteins. Immunoprecipitation experiments show that the RA corepressor SMRT physically associates with AhR in a breast cancer cell line (37) and that the RA coactivator CBP/p300 interacts with the C-terminal domain of Arnt (38). Nuclear receptor corepressors are reported to function by causing deacetylation of adjacent chromatin structures resulting in transcriptional silencing (39 -41).…”

Section: Discussionmentioning

confidence: 99%

Interaction between the Aryl Hydrocarbon Receptor and Retinoic Acid Pathways Increases Matrix Metalloproteinase-1 Expression in Keratinocytes

Murphy

Villano

Dorn

et al. 2004

Journal of Biological Chemistry

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Exposure to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) results in a variety of pathological lesions in humans via activation of the aryl hydrocarbon receptor (AhR) pathway. It has become apparent that this pathway interacts with a variety of signaling pathways that are believed to be involved in mediating TCDD/AhR biological effects. Our hypothesis is that TCDD mediates these pathological lesions by directly altering the expression of genes involved in matrix deposition and remodeling and that the retinoic acid signaling pathway is involved in modulating TCDD-induced effects. Therefore, we examined the effect of TCDD and all-trans retinoic acid (atRA) on the expression of matrix metalloproteinase-1 (MMP-1, interstitial collagenase), one of the proteolytic enzymes that degrade type I collagen, in normal human keratinocytes. The data show that TCDD exposure results in increased MMP-1 expression in keratinocytes that is further enhanced by co-treatment with all-trans retinoic acid. TCDD-induced expression of MMP-1 appears to be mediated through two AP-1 elements in the proximal promoter of the MMP-1 gene. However, retinoic acid-mediated induction of keratinocyte MMP-1 is a result of both promoter activation and increased mRNA stability. These findings are the first to demonstrate TCDD-induced expression of MMP-1 and to demonstrate interactions between the TCDD/AhR and retinoic acid pathways on MMP-1 expression.Exposure to the polycyclic aromatic hydrocarbon 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) 1 results in a number of pathological lesions involving matrix deposition and tissue remodeling, including prostate and mammary tubule morphogenesis, palatal development, and tumor promotion (1-3). We hypothesize that TCDD mediates these pathological lesions by altering the expression of genes involved in matrix remodeling.Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade the protein components of the extracellular matrix. MMP expression is integral to processes in skin remodeling and inappropriate expression and activity of MMPs is associated with a variety of pathologies such as rheumatoid arthritis and tumor metastasis (4 -6). Regulation of MMPs occurs primarily at the levels of transcription and activity (7). Investigation into MMP gene expression have identified several cis-and trans-acting factors that are involved in MMP-1 transcriptional activation, including several AP-1 sites and PEA-3 elements, that contribute to MMP-1 gene expression (8, 9).The primary mechanism of TCDD-induced changes in gene expression is through activation of the aryl hydrocarbon receptor (AhR)/aryl hydrocarbon receptor nuclear translocator (Arnt) transcription pathway. AhR and its dimerization partner, Arnt, are members of the basic helix-loop-helix PAS (bHLH-PAS) domain family of transcription factors. Proteins in this family have diverse biological roles ranging from regulation of development, hypoxia signaling, and circadian rhythms (reviewed in Ref.

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Section: Discussionmentioning

confidence: 99%

Interaction between the Aryl Hydrocarbon Receptor and Retinoic Acid Pathways Increases Matrix Metalloproteinase-1 Expression in Keratinocytes

Murphy

Villano

Dorn

et al. 2004

Journal of Biological Chemistry

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“…Arnt probably associates with transcriptional co-activator CBP/p300. (Kobayashi et al, 1997;Vaziri et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Epstein–Barr virus encoded nuclear protein EBNA-3 binds XAP-2, a protein associated with Hepatitis B virus X antigen

et al. 2000

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“…In addition, the ability of E2F to act as an activator of transcription depends in part on an interaction with the HDACs p300/CBP and p/CAF (70,71). A role for corepressor/coactivator activities is also recognized as important for the regulation of the AHR complex (46,72). We therefore tested the dependence of AHR transcriptional repression on specific corepressor and coactivator activities required for normal E2F-dependent regulation of transcription.…”

Section: Tcdd Reverses P300-mediated Induction Of E2f-dependentmentioning

confidence: 99%

The Aryl Hydrocarbon Receptor Displaces p300 from E2F-dependent Promoters and Represses S Phase-specific Gene Expression

Marlowe

Knudsen

Schwemberger³

et al. 2004

Journal of Biological Chemistry

142

122

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The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes a wide range of toxic, teratogenic, and carcinogenic effects. TCDD is a ligand for the aromatic hydrocarbon receptor (AHR), a ligand-activated transcription factor believed to be the primary mediator of these effects. Activation of the AHR by TCDD also elicits a variety of effects on cell cycle progression, ranging from proliferation to arrest. In this report, we have characterized further the role of the activated AHR in cell cycle regulation. In human mammary carcinoma MCF-7 and mouse hepatoma Hepa-1 cells, TCDD treatment decreased the number of cells in S phase and caused the accumulation of cells in G 1 . In Hepa-1 cells, this effect correlated with the transcriptional repression of several E2F-regulated genes required for S phase progression. AHR-mediated gene repression was dependent on its interaction with retinoblastoma protein but was independent of its transactivation function because AHR mutants lacking DNA binding or transactivation domains repressed E2F-dependent expression as effectively as wild type AHR. Overexpression of p300 suppressed retinoblastoma protein-dependent gene repression, and this effect was reversed by TCDD. Chromatin immunoprecipitation assays showed that TCDD treatment caused the recruitment of AHR to E2F-dependent promoters and the concurrent displacement of p300. These results delineate a novel mechanism whereby the AHR, a known transcriptional activator, also mediates gene repression by pathways involving combinatorial interactions at E2F-responsive promoters, leading to the repression of E2F-dependent, S phase-specific genes. The AHR seems to act as an environmental checkpoint that senses exposure to environmental toxicants and responds by signaling cell cycle inhibition.2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) 1 is the prototypical compound of a class of environmental contaminants that includes many halogenated aromatic hydrocarbons and polycyclic aromatic hydrocarbons and is a model for the outcome of exposure to these compounds as well as coplanar polychlorinated biphenyls. Exposure to TCDD results in a plethora of toxic and carcinogenic responses in animals, including liver toxicity (1), immunosuppression (2, 3), reproductive and developmental dysfunction (4 -6), endometriosis (7,8), and tumor promotion (9). The most immediate exposure outcome in humans is chloracne (10). Long term effects in humans range from immunological and reproductive perturbations (11) to cardiovascular disease (12, 13) and cancer (14 -18). TCDD itself is poorly metabolized, which leads to biological accumulation and production of sustained effects (19).Although the in vivo effects of TCDD are wide ranging, the in vitro effects are just as varied and often contradictory, affecting cell proliferation, apoptosis, and differentiation, depending on the cell type examined. TCDD acts as an endocrine disruptor in cell cultures, inhibiting several estrogen-induced responses such as growth of human mammary and endometrial canc...

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CBP/p300 Functions as a Possible Transcriptional Coactivator of Ah Receptor Nuclear Translocator (Arnt)

Cited by 164 publications

References 0 publications

Interaction between the Aryl Hydrocarbon Receptor and Retinoic Acid Pathways Increases Matrix Metalloproteinase-1 Expression in Keratinocytes

Interaction between the Aryl Hydrocarbon Receptor and Retinoic Acid Pathways Increases Matrix Metalloproteinase-1 Expression in Keratinocytes

Epstein–Barr virus encoded nuclear protein EBNA-3 binds XAP-2, a protein associated with Hepatitis B virus X antigen

The Aryl Hydrocarbon Receptor Displaces p300 from E2F-dependent Promoters and Represses S Phase-specific Gene Expression

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