Opposite effects of CBP and p300 in glucocorticoid signaling in astrocytes

Fonte, Cosima; Trousson, Amalia; Grenier, Julien; Schumacher, Michaël; Massaad, Charbel

doi:10.1016/j.jsbmb.2007.03.034

Cited by 12 publications

(8 citation statements)

References 41 publications

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“…The recruitment of CBP to GR upon TNF pretreatment, as found in the BioID study, can have an additional value in the establishment of TNF-induced GCR. Despite the fact that CBP and p300 are close homologs, opposing effects of CBP and p300 in GC signaling have been described in the past (49). Mounting the cofactor exchange model to the full, we might hypothesize that TNF pretreatment not only may recruit p300 to p65, resulting in reduced GR TA, but that, at the same time, that CBP may replace the p300 position on GR, leading to inhibition of the GR function even more.…”

Section: Discussionmentioning

confidence: 99%

TNF-α inhibits glucocorticoid receptor-induced gene expression by reshaping the GR nuclear cofactor profile

Dendoncker

Timmermans

Vandewalle

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Glucocorticoid resistance (GCR) is defined as an unresponsiveness to the therapeutic effects, including the antiinflammatory ones of glucocorticoids (GCs) and their receptor, the glucocorticoid receptor (GR). It is a problem in the management of inflammatory diseases and can be congenital as well as acquired. The strong proinflammatory cytokine TNF-alpha (TNF) induces an acute form of GCR, not only in mice, but also in several cell lines: e.g., in the hepatoma cell line BWTG3, as evidenced by impaired Dexamethasone (Dex)-stimulated direct GR-dependent gene up- and down-regulation. We report that TNF has a significant and broad impact on this transcriptional performance of GR, but no impact on nuclear translocation, dimerization, or DNA binding capacity of GR. Proteome-wide proximity-mapping (BioID), however, revealed that the GR interactome was strongly modulated by TNF. One GR cofactor that interacted significantly less with the receptor under GCR conditions is p300. NFκB activation and p300 knockdown both reduced direct transcriptional output of GR whereas p300 overexpression and NFκB inhibition reverted TNF-induced GCR, which is in support of a cofactor reshuffle model. This hypothesis was supported by FRET studies. This mechanism of GCR opens avenues for therapeutic interventions in GCR diseases.

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Section: Discussionmentioning

confidence: 99%

TNF-α inhibits glucocorticoid receptor-induced gene expression by reshaping the GR nuclear cofactor profile

Dendoncker

Timmermans

Vandewalle

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…Among the various HAT families, CBP, p300 and PCAF (as a component of ADA (Ada acetyltransferase) and SAGA (Spt-Ada-Gcn5-acetyltransferase) complexes) interact with GR directly, through interactions with the AF1 domain, or indirectly, through pl60 co-regulators associated with the AF2 domain of GR, to modulate transcription 100,124,157–159 . HATs target histones as well as non-histone proteins (including nuclear receptors) in a context-specific manner 117,160 and, although they are generally associated with activation of transcription 161 , their mechanisms of action and regulatory outcomes seem also to be context-dependent 162 .…”

Section: Co-regulators As Gr Signalling Readersmentioning

confidence: 99%

Glucocorticoid receptor control of transcription: precision and plasticity via allostery

Weikum

Knuesel

Ortlund

et al. 2017

Nat Rev Mol Cell Biol

427

419

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The glucocorticoid receptor (GR) is a constitutively expressed transcriptional regulatory factor (TRF) that controls many distinct gene networks, each uniguely determined by particular cellular and physiological contexts. The precision of GR-mediated responses seems to depend on combinatorial, context-specific assembly of GR-nucleated transcription regulatory complexes at genomic response elements. In turn, evidence suggests that context-driven plasticity is conferred by the integration of multiple signals, each serving as an allosteric effector of GR conformation, a key determinant of regulatory complex composition and activity. This structural and mechanistic perspective on GR regulatory specificity is likely to extend to other eukaryotic TRFs.

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“…Previous in vitro studies have shown that SRC-1 is a co-activator for GR in Schwann cells and astrocytes (Grenier et al 2004 and, whereas CBP/p300 is a repressor of GR in Schwann cells and in astrocytes (Fonte et al 2007). There has also been a report of the co-expression of SRC-1 and p300 in the adult rat brain (Ogawa et al 2001).…”

Section: Discussionmentioning

confidence: 98%

Distribution of Corticosteroid Receptors in Mature Oligodendrocytes and Oligodendrocyte Progenitors of the Adult Mouse Brain

Matsusue

Horii-Hayashi

Kirita

et al. 2013

J Histochem Cytochem.

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SummaryThe expression of glucocorticoid receptors (GRs) was investigated immunohistochemically in two different lineages of oligodendrocytes, using carbonic anhydrase (CA) II and neuron glial antigen (NG) 2 as markers of mature oligodendrocytes and oligodendrocyte progenitors, respectively. We focused on the gray matter regions, including CA1, CA3 and the dentate gyrus of the hippocampus, the primary somatosensory cortex barrel field and the basolateral amygdala, and the white matter regions, including the corpus callosum, external capsule and fimbria of the hippocampus. More than 80% of CAIIimmunoreactive (IR) cells and more than 95% of NG2-IR cells expressed GRs in various regions of the brain. In contrast, neither CAII-IR cells nor NG2-IR cells expressed mineralocorticoid receptors (MRs) in the same regions. The intensity of GR expression was drastically reduced in CA II-IR cells and NG2-IR cells in the same regions in adrenalectomized mice. Finally, steroid receptor co-activator (SRC)-1 and p300, both of which are cofactors for GR, were expressed in the gray and white matter regions in NG2-IR cells, but not in CAII-IR cells. These results suggest that the expression of GRs in oligodendrocytes and their progenitor cells mediates several functions in vivo, including differentiation and myelination, as a major target of glucocorticoids and their cofactors. (J Histochem Cytochem 62:211-226, 2014)

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Opposite effects of CBP and p300 in glucocorticoid signaling in astrocytes

Cited by 12 publications

References 41 publications

TNF-α inhibits glucocorticoid receptor-induced gene expression by reshaping the GR nuclear cofactor profile

TNF-α inhibits glucocorticoid receptor-induced gene expression by reshaping the GR nuclear cofactor profile

Glucocorticoid receptor control of transcription: precision and plasticity via allostery

Distribution of Corticosteroid Receptors in Mature Oligodendrocytes and Oligodendrocyte Progenitors of the Adult Mouse Brain

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