Transcriptional regulation by the phosphorylation-dependent factor CREB
01 Aug 2001-Nature Reviews Molecular Cell Biology (Nature Publishing Group)-Vol. 2, Iss: 8, pp 599-609
TL;DR: The transcription factor CREB functions in glucose homeostasis, growth-factor-dependent cell survival, and has been implicated in learning and memory, and how is specificity achieved in these signalling pathways?
Abstract: The transcription factor CREB -- for 'cyclic AMP response element-binding protein' -- functions in glucose homeostasis, growth-factor-dependent cell survival, and has been implicated in learning and memory. CREB is phosphorylated in response to various signals, but how is specificity achieved in these signalling pathways?
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TL;DR: This review focuses on the current level of understanding of where, when, and how CREB family members function in the nervous system.
1,984 citations
Cites background from "Transcriptional regulation by the p..."
...domain, which is consistent with the findings that these factors can form both homo- and heterodimers, and that each can bind to the same cis-regulatory element (reviewed in De Cesare et al., 1999; Mayr and Montminy, 2001; Shaywitz and Greenberg, 1999)....
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TL;DR: These transcriptional paradigms provide a basic framework for understanding the integration of mitochondrial biogenesis and function with signaling events that dictate cell- and tissue-specific energetic properties.
Abstract: Mitochondria contain their own genetic system and undergo a unique mode of cytoplasmic inheritance. Each organelle has multiple copies of a covalently closed circular DNA genome (mtDNA). The entire...
1,401 citations
Cites background from "Transcriptional regulation by the p..."
...CREB is well known as a target of mitogenic signaling pathways (137)....
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...Although CREB sites are common to cAMP- and growthactivated genes (137), these elements are not a general feature of nuclear respiratory promoters....
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TL;DR: Perturbations in the balance between synaptic and extrasynaptic NMDAR activity contribute to neuronal dysfunction in acute ischaemia and Huntington's disease, and could be a common theme in the aetiology of neurodegenerative diseases.
Abstract: There is a long-standing paradox that NMDA (N-methyl-D-aspartate) receptors (NMDARs) can both promote neuronal health and kill neurons. Recent studies show that NMDAR-induced responses depend on the receptor location: stimulation of synaptic NMDARs, acting primarily through nuclear Ca(2+) signalling, leads to the build-up of a neuroprotective 'shield', whereas stimulation of extrasynaptic NMDARs promotes cell death. These differences result from the activation of distinct genomic programmes and from opposing actions on intracellular signalling pathways. Perturbations in the balance between synaptic and extrasynaptic NMDAR activity contribute to neuronal dysfunction in acute ischaemia and Huntington's disease, and could be a common theme in the aetiology of neurodegenerative diseases. Neuroprotective therapies should aim to both enhance the effect of synaptic activity and disrupt extrasynaptic NMDAR-dependent death signalling.
1,373 citations
TL;DR: It is concluded that astrocyte-neuron lactate transport is required for long-term memory formation, suggesting that lactate import into neurons is necessary for long -term memory.
1,255 citations
Cites background from "Transcriptional regulation by the p..."
...Toward this end, we investigated the induction of Arc expression, ser 133 pCREB, which is known to be critical for CREB-dependent gene expression regulation (Alberini, 2009; Mayr and Montminy, 2001) and the phosphorylation of cofilin (pcofilin)....
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TL;DR: Emerging evidence suggests that strategies that exploit regional differences in upstream factors or that target specific CREB-regulated genes, rather than CREB itself, could make a promising contribution to the treatment of neuropsychiatric conditions.
1,238 citations
References
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TL;DR: Results suggest that phosphorylation of CREB may stimulate transcription by a mechanism other than by simply providing negative charge, as CREB mutants containing acidic residues in place of the Ser-133 phosphoacceptor were also transcriptionally inactive.
2,456 citations
"Transcriptional regulation by the p..." refers background in this paper
...Induction of cAMP liberates the C subunits, which passively diffuse into the nucleus and induce cellular gene expression by phosphorylating CREB at serine residue 133 (Ref...
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TL;DR: It is proposed that CBP may participate in cAMP-regulated gene expression by interacting with the activated phosphorylated form of CREB, which is activated as a result of phosphorylation by protein kinase A7.
Abstract: Cyclic AMP-regulated gene expression frequently involves a DNA element known as the cAMP-regulated enhancer (CRE). Many transcription factors bind to this element, including the protein CREB, which is activated as a result of phosphorylation by protein kinase A. This modification stimulates interaction with one or more of the general transcription factors or, alternatively, allows recruitment of a co-activator. Here we report that CREB phosphorylated by protein kinase A binds specifically to a nuclear protein of M(r) 265K which we term CBP (for CREB-binding protein). Fusion of a heterologous DNA-binding domain to the amino terminus of CBP enables the chimaeric protein to function as a protein kinase A-regulated transcriptional activator. We propose that CBP may participate in cAMP-regulated gene expression by interacting with the activated phosphorylated form of CREB.
2,041 citations
TL;DR: The findings suggest that the MAPK signaling pathway promotes cell survival by a dual mechanism comprising the posttranslational modification and inactivation of a component of the cell death machinery and the increased transcription of pro-survival genes.
Abstract: A mechanism by which the Ras–mitogen-activated protein kinase (MAPK) signaling pathway mediates growth factor–dependent cell survival was characterized. The MAPK-activated kinases, the Rsks, catalyzed the phosphorylation of the pro-apoptotic protein BAD at serine 112 both in vitro and in vivo. The Rsk-induced phosphorylation of BAD at serine 112 suppressed BAD-mediated apoptosis in neurons. Rsks also are known to phosphorylate the transcription factor CREB (cAMP response element–binding protein) at serine 133. Activated CREB promoted cell survival, and inhibition of CREB phosphorylation at serine 133 triggered apoptosis. These findings suggest that the MAPK signaling pathway promotes cell survival by a dual mechanism comprising the posttranslational modification and inactivation of a component of the cell death machinery and the increased transcription of pro-survival genes.
1,944 citations
"Transcriptional regulation by the p..." refers background in this paper
...A role for CREB in growth-factor-dependent survival has been shown in sympathetic and cerebellar neuron...
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TL;DR: Consistent with models claiming a role for long-term potentiation (LTP) in memory, LTP in hippocampal slices from CREB mutants decayed to baseline 90 min after tetanic stimulation, however, paired-pulse facilitation and posttetanic potentiation are normal.
1,832 citations
"Transcriptional regulation by the p..." refers background in this paper
...Disruption of the α- and δ-isoforms of CREB in mice, for example, leads to defects in long-term potentiation and long-term memor...
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TL;DR: Fluorescence anisotropy measurements are used to define the equi-librium binding parameters of the phosphoCREB:CBP interaction and report here that CBP can activate transcription through a region in its carboxy terminus.
Abstract: The transcription factor CREB binds to a DNA element known as the cAMP-regulated enhancer (CRE). CREB is activated through phosphorylation by protein kinase A (PKA), but precisely how phosphorylation stimulates CREB function is unknown. One model is that phosphorylation may allow the recruitment of coactivators which then interact with basal transcription factors. We have previously identified a nuclear protein of M(r)265K, CBP, that binds specifically to the PKA-phosphorylated form of CREB. We have used fluorescence anisotropy measurements to define the equilibrium binding parameters of the phosphoCREB:CBP interaction and report here that CBP can activate transcription through a region in its carboxy terminus. The activation domain of CBP interacts with the basal transcription factor TFIIB through a domain that is conserved in the yeast coactivator ADA-1 (ref. 8). Consistent with its role as a coactivator, CBP augments the activity of phosphorylated CREB to activate transcription of cAMP-responsive genes.
1,471 citations
"Transcriptional regulation by the p..." refers background in this paper
...Phosphorylation of Ser133 potentiates activity of the KID by promoting recruitment of the co-activator paralogues CBP and p300 to the promote...
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