CCAAT/Enhancer-binding Protein Family Members Recruit the Coactivator CREB-binding Protein and Trigger Its Phosphorylation

Kovács, Krisztián A.; Steinmann, Myriam; Magistretti, Pierre J.; Halfon, Olivier; Cardinaux, Jean‐René

doi:10.1074/jbc.m303147200

Cited by 132 publications

(122 citation statements)

References 70 publications

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“…The current paradigm of CBP/p300 action suggests that CBP/p300 activity is mediated by competition of various promoter elements for limited quantities of CBP/p300. However, recent studies suggest that the activity of CBP may also be controlled by phosphorylation, although correlation between specific sites of phosphorylation and alteration of function has been rare (Kovacs et al, 2003). Given our recent observations regarding (1) the role of AKT in regulating Tam-induced apoptosis and (2) Tam-modulated CBP recruitment to the IRF-1 GAS element, we are currently investigating the potential role of AKT in promoting CBP recruitment and IRF-1 induction.…”

Section: Discussionmentioning

confidence: 99%

Interferon-regulatory factor-1 is critical for tamoxifen-mediated apoptosis in human mammary epithelial cells

et al. 2004

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Unlike estrogen receptor-positive (ER( þ )) breast cancers, normal human mammary epithelial cells (HMECs) typically express low nuclear levels of ER (ER poor). We previously demonstrated that 1.0 lM tamoxifen (Tam) promotes apoptosis in acutely damaged ER-poor HMECs through a rapid, 'nonclassic' signaling pathway. Interferon-regulatory factor-1 (IRF-1), a target of signal transducer and activator of transcription-1 transcriptional regulation, has been shown to promote apoptosis following DNA damage. Here we show that 1.0 lM Tam promotes apoptosis in acutely damaged ER-poor HMECs through IRF-1 induction and caspase-1/3 activation. Treatment of acutely damaged HMEC-E6 cells with 1.0 lM Tam resulted in recruitment of CBP to the c-IFN-activated sequence element of the IRF-1 promoter, induction of IRF-1, and sequential activation of caspase-1 and -3. The effects of Tam were blocked by expression of siRNA directed against IRF-1 and caspase-1 inhibitors. These data indicate that Tam induces apoptosis in HMEC-E6 cells through a novel IRF-1-mediated signaling pathway that results in activated caspase-1 and -3.

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Section: Discussionmentioning

confidence: 99%

Interferon-regulatory factor-1 is critical for tamoxifen-mediated apoptosis in human mammary epithelial cells

et al. 2004

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“…The results showed that C/EBPa, C/EBPb, and C/EBPd interact with the ET-1 promoter in the genomic regions displaying the predicted elements. It is noteworthy that in addition to the canonical interactions, several mechanisms of C/EBP-induced gene transcription have been demonstrated including interplays with other transcription factors such as (NF-kB, AP-1, Sp1, CREB) [37][38][39][40] or recruitment of various transcriptional co-regulators that affect chromatin conformation, a condition that untimely facilitates the trapping of basal transcription factors. [41,42] Based on that fact that NF-kB and AP-1 are direct regulators of ET-1 transcription, the existence of non-canonical associations among transcriptional complexes formed by heterodimers consisting of C/EBP and other transcription factors that might or might not contain the basicleucine zipper domain [18] should be considered as well.…”

Section: Discussionmentioning

confidence: 99%

High glucose-induced increased expression of endothelin-1 in human endothelial cells is mediated by activated CCAAT/enhancer-binding proteins

Manea¹,

Todirita²,

Heltianu³

et al. 2013

European Heart Journal

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High glucose-induced endothelial dysfunction is partially mediated by the down-stream pathophysiological effects triggered by increased expression of endothelin-1 (ET-1). The molecular control mechanisms of ET-1 synthesis are yet to be discovered. Members of the CCAAT/enhancer-binding proteins (C/EBP) family are important regulators of key metabolic processes, cellular differentiation and proinflammatory genes. In this study, we aimed at elucidating the role of C/EBP in mediating the high glucose effect on ET-1 expression in human endothelial cells (EC). Human umbilical vein cells (EAhy926) and primary cultures of human aortic EC were exposed to high levels of glucose (16.5-25 mM). Real-time PCR, Western blot, enzyme-linked immunosorbent assay, ET-1 promoter-luciferase reporter analysis, and chromatin immunoprecipitation assays were employed to investigate ET-1 regulation. High glucose activated C/EBPa, C/EBPb, and C/EBPd in a dosedependent manner. It also promoted significant increases in ET-1 gene and peptide expression. Chemical inhibition of JNK, p38MAPK and ERK1/2 diminished significantly the high glucose-induced nuclear translocation of C/EBP and ET-1 expression. Silencing of C/EBPa, C/EBPb or C/EBPd greatly reduced the high glucose-induced upregulation of ET-1 mRNA, pre-pro-ET-1, and ET-1 secretion. The expression of various C/EBP isoforms was selectively downregulated by siRNA-mediated gene silencing. In silico analysis indicated the existence of typical C/EBP elements within human ET-1 gene promoter. Transient overexpression of C/EBPa, C/EBPb or C/EBPd upregulated the luciferase level controlled by the ET-1 gene promoter. The direct interaction of C/EBPa, C/EBPb or C/EBPd proteins with the ET-1 promoter in high glucose-exposed EC was confirmed by chromatin immunoprecipitation assay. High glucose-induced ET-1 expression is mediated through multiple mechanisms. We present evidence that members of the C/EBP proinflammatory transcription factors are important regulators of ET-1 in high glucose-exposed human endothelial cells. High glucose-induced activation of C/EBP-related signaling pathways may induce excessive ET-1 synthesis, thus promoting vasoconstriction and dysfunction of the vascular wall cells in diabetes.

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“…The Gal4-Luc reporter gene is described in ref. 38. pcDNA3-GAL-CREB constructs are described in SI Materials and Methods.…”

Section: Methodsmentioning

confidence: 99%

TORC1 is a calcium- and cAMP-sensitive coincidence detector involved in hippocampal long-term synaptic plasticity

Kovács

Steullet

Steinmann

et al. 2007

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

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A key feature of memory processes is to link different input signals by association and to preserve this coupling at the level of synaptic connections. Late-phase long-term potentiation (L-LTP), a form of synaptic plasticity thought to encode long-term memory, requires gene transcription and protein synthesis. In this study, we report that a recently cloned coactivator of cAMP-response elementbinding protein (CREB), called transducer of regulated CREB activity 1 (TORC1), contributes to this process by sensing the coincidence of calcium and cAMP signals in neurons and by converting it into a transcriptional response that leads to the synthesis of factors required for enhanced synaptic transmission. We provide evidence that TORC1 is involved in L-LTP maintenance at the Schaffer collateral-CA1 synapses in the hippocampus.BDNF ͉ calcineurin ͉ cAMP-response element-binding protein ͉ long-term potentiation ͉ memory T ransducers of regulated cAMP-response element-binding protein (CREB) activity (TORCs) are newly discovered coactivators that dramatically increase CREB's transcriptional activity independently of CREB Ser-133 phosphorylation (1, 2). Recently, it has been shown that TORC2 functions as a pancreatic coincidence detector. In insulinoma cells, glucose and gut hormones, via respective activation of L-type calcium channels and the cAMP pathway, synergistically promote the dephosphorylation and the concomitant nuclear translocation of TORC2 (3). In the brain, encoding and storing associative memories requires detection of the coincidence of different input signals and translation of these associations into changes in the number, structure, or function of synapses. Therefore, it appears that short-lived coincidences result in the transcriptional activation of genes encoding factors required for enhanced synaptic transmission. TORCs present two features that neurons could use to create an association: they can detect the coincidence of the two most important second messengers, calcium and cAMP, and they are potent coactivators of CREB, a transcription factor known to drive the expression of genes underlying synaptic plasticity, late-phase long-term potentiation (L-LTP), learning, and memory (4-7).CREB-dependent promoters have been generally thought to respond to various intracellular and extracellular cues by the stimulus-dependent phosphorylation of CREB at Ser-133 and resultant recruitment of the coactivator CREB binding protein (CBP) (5,6,8,9). Modification of CREB at this site often mirrors the activation of neurons, leading to the idea that the expression of plasticity-related genes relies on CREB/CBP interaction. However, some studies revealing a discrepancy between CREB phosphorylation and CREB-mediated gene transcription have challenged this model. For instance, monocular deprivation induces LacZ expression in the visual cortex of cAMP-response element (CRE)-LacZ transgenic mice (10), whereas phosphorylation of CREB at Ser-133 remains static (11). Similarly, the mechanism underlying CREB activation during L...

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CCAAT/Enhancer-binding Protein Family Members Recruit the Coactivator CREB-binding Protein and Trigger Its Phosphorylation

Cited by 132 publications

References 70 publications

Interferon-regulatory factor-1 is critical for tamoxifen-mediated apoptosis in human mammary epithelial cells

Interferon-regulatory factor-1 is critical for tamoxifen-mediated apoptosis in human mammary epithelial cells

High glucose-induced increased expression of endothelin-1 in human endothelial cells is mediated by activated CCAAT/enhancer-binding proteins

TORC1 is a calcium- and cAMP-sensitive coincidence detector involved in hippocampal long-term synaptic plasticity

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