Fragile X syndrome is caused by lack of fragile X mental retardation protein (FMRP) due to silencing of the FMR1 gene. The metabotropic glutamate receptors (mGluRs) in the central nervous system contribute to higher brain functions including learning/memory, mental disorders and persistent pain. The transcription factor cyclic AMP-responsive element binding protein (CREB) is involved in important neuronal functions, such as synaptic plasticity and neuronal survival. Our recent study has shown that stimulation of Group I mGluRs upregulated FMRP and activated CREB in anterior cingulate cortex (ACC), a key region for brain cognitive and executive functions, suggesting that activation of Group I mGluRs may upregulate FMRP through CREB signaling pathway. In this study, we demonstrate that CREB contributes to the regulation of FMRP by Group I mGluRs. In ACC neurons of adult mice overexpressing dominant active CREB mutant, the upregulation of FMRP by stimulating Group I mGluR is enhanced compared to wild-type
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TY - JOUR. T1 - Discovery of a Synergistic Inhibitor of cAMP-Response Element Binding Protein (CREB)-Mediated Gene Transcription with 666 - 15. AU - Xie, Fuchun. AU - Fan, Qiuhua. AU - Li, Bingbing X.. AU - Xiao, Xiangshu. PY - 2019/1/1. Y1 - 2019/1/1. N2 - CREB is a transcription factor implicated in the pathogenesis of multiple cancers. Targeting CREB is a promising strategy to develop potential cancer therapeutics. Previously, we identified 666-15 as a potent CREB inhibitor. Herein, we designed an ester prodrug of 666-15 through a long-range O,N-acyl transfer reaction for improved aqueous solubility. Unexpectedly, we discovered a small molecule 11 (653-47) that can potentiate the CREB inhibitory activity of 666-15 although 653-47 alone does not inhibit CREB.. AB - CREB is a transcription factor implicated in the pathogenesis of multiple cancers. Targeting CREB is a promising strategy to develop potential cancer therapeutics. Previously, we identified 666-15 as a potent CREB inhibitor. Herein, ...
ATM has been shown to have important roles in the transcriptional regulation of gene expression by phosphorylation of transcription factors, such as p53, nuclear factor κB, E2F, cyclic AMP-responsive element binding protein, and BRCA1, and in maintenance of the normal functions of IGF-IR and telomeres (3, 13, 14, 32). ATM-dependent gene expression has been systematically studied by comparing cell lines from normal individuals and AT patients, isogenic cell lines with restoration of ATM in AT cells or small interfering RNA knockdown of ATM in wild-type cells, and ATM+/+/ATM−/− mice (3, 13, 21-23). More than 300 genes have been reported to display ATM-dependent expression although few genes were commonly identified in two or more experiments. The microarray results presented here identified 160 genes or expressed sequence tags (∼1% of the total on the array) that were differentially expressed in normal and AT fibroblast lines under basal growth conditions, of which about half were ...
Lysosomal-associated protein transmembrane-4 beta (LAPTM4B) is a potential proto-oncogene, whose overexpression is involved in cancer occurrence and progression. Its transcript is up-regulated in various types of solid tumors including breast cancer. However, its transcriptional regulation mechanism is still unclear. To investigate the mechanism of transcriptional regulation of LAPTM4B in human breast cancer cells, a series of luciferase reporter constructs and construct with mutated binding site for cAMP responsive element binding protein-1 (CREB1) were generated by PCR amplification and transiently transfected into breast cancer cells to determine the transcriptional activities of different promoter regions. The + 10 similar to+ 292 promoter region was possessed the highest transcriptional activity. The ability of CREB1 to bind the LAPMT4B promoter was confirmed by electrophoretic mobility shift assay, super-shift and RNA interference experiments. Our study identified the core promoter region ...
Phosphorylation-dependent transcription factor that stimulates transcription upon binding to the DNA cAMP response element (CRE), a sequence present in many viral and cellular promoters. Transcription activation is enhanced by the TORC coactivators which act independently of Ser-117 phosphorylation. Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells (By similarity).
TY - JOUR. T1 - Design, synthesis and biological evaluation of regioisomers of 666-15 as inhibitors of CREB-mediated gene transcription. AU - Xie, Fuchun. AU - Li, Bingbing X.. AU - Xiao, Xiangshu. PY - 2016/11/3. Y1 - 2016/11/3. N2 - cAMP-response element binding protein (CREB) is a nuclear transcription factor that has been implicated in the pathogenesis and maintenance of various types of human cancers. Identification of small molecule inhibitors of CREB-mediated gene transcription has been pursued as a novel strategy for developing cancer therapeutics. We recently discovered a potent and cell-permeable CREB inhibitor called 666-15. 666-15 is a bisnaphthamide and has been shown to possess efficacious anti-breast cancer activity without toxicity in vivo. In this study, we designed and synthesized a series of analogs of 666-15 to probe the importance of regiochemistry in naphthalene ring B. Biological evaluations of these analogs demonstrated that the substitution pattern of the alkoxy and ...
BioMed Research International is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies covering a wide range of subjects in life sciences and medicine. The journal is divided into 55 subject areas.
TY - JOUR. T1 - Nuclear factor-kappaB and cAMP response element binding protein mediate opposite transcriptional effects on the Flk-1/KDR gene promoter.. AU - Illi, B.. AU - Puri, P.. AU - Morgante, L.. AU - Capogrossi, M. C.. AU - Gaetano, C.. PY - 2000/6/23. Y1 - 2000/6/23. N2 - -The vascular endothelial growth factor receptor Flk-1/KDR is highly expressed during development and almost disappears in adult tissues. Despite its biological relevance, little is known about the molecular mechanisms controlling its expression. In the present work, it is shown that cAMP response element binding protein (CREB) and nuclear factor-kappaB (NF-kappaB)-related antigens bind specific sequences in the Flk-1/KDR promoter. Functional studies demonstrate that cAMP represses whereas tumor necrosis factor-alpha, an activator of NF-kappaB, stimulates promoter activity. Histone acetyltransferases (HATs) P/CAF and CBP/p300 together with p65/RelA, the catalytic subunit of NF-kappaB, increase Flk-1/KDR promoter ...
The results reveal an essential survival pathway in malignant glioma, whereby activation of a RAS-mitogen-activated protein kinase or phosphoinositide-3-kinase signaling cascade leads to induction of the transcription factor cAMP response element-binding protein-3-like-2 (CREB3L2), which directly activates ATF5 expression. ATF5, in turn, promotes survival by stimulating transcription of myeloid cell leukemia sequence-1 (MCL1), an antiapoptotic B cell leukemia-2 family member. [Nat Med ...
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TY - JOUR. T1 - Relaxin activates peroxisome proliferator-activated receptor γ(PPAR γ)through a pathway involving PPAR γ coactivator 1α (PGC1α). AU - Singh, Sudhir. AU - Simpson, Ronda L.. AU - Bennett, Robert G.. PY - 2015/1/9. Y1 - 2015/1/9. N2 - Relaxin activation of its receptor RXFP1 triggers multiple signaling pathways. Previously, we have shown that relaxin activates &gamma transcriptional activity in a ligand-independent manner, but the mechanism for this effect was unknown. In this study, we examined the signaling pathways of downstream of RXFP1 leading to γ activation. Using cells stably expressing RXFP1, we found that relaxin regulation of &gamma activity requires accumulation of cAMP and subsequent activation of cAMP-dependent protein kinase (PKA). The activated PKA subsequently phosphorylated cAMP response element-binding protein (CREB) at Ser-133 to activate it directly, as well as indirectly through mitogen activated protein kinase p38 MAPK. Activated CREB was required for ...
TransAM CREB and TransAM pCREB Kits are DNA-binding ELISAs that quanify the activated transcription factors using a method that is faster and more sensitive than gelshift, without radioactivity and gels.
Background: Lowered sensitivity to the effects of ethanol increases the risk of developing alcoholism. Inbred mouse strains have been useful for the study of the genetic basis of various drug addiction-related phenotypes. Inbred Long-Sleep (ILS) and Inbred Short-Sleep (ISS) mice differentially express a number of genes thought to be implicated in sensitivity to the effects of ethanol. Concomitantly, there is evidence for a mediating role of cAMP/PKA/CREB signalling in aspects of alcoholism modelled in animals. In this report, the extent to which CREB signalling impacts the differential expression of genes in ILS and ISS mouse cerebella is examined. Results: A training dataset for Machine Learning (ML) and Exploratory Data Analyses (EDA) was generated from promoter region sequences of a set of genes known to be targets of CREB transcription regulation and a set of genes whose transcription regulations are potentially CREB-independent. For each promoter sequence, a vector of size 132, with ...
cAMP response element (CRE)-binding protein-like-2 (CREBL2) was identified in a search to find genes in a commonly deleted region on chromosome 12p13 flanked by ETV6 and CDKN1B genes, frequently associated with hematopoietic malignancies, as well as breast, non-small-cell lung and ovarian cancers. CREBL2 shares a 41% identity with CRE-binding protein (CREB) over a 48-base long region which encodes the bZip domain of CREB. The bZip domain consists of about 30 amino acids rich in basic residues involved in DNA binding, followed by a leucine zipper motif involved in protein dimerization. This suggests that CREBL2 encodes a protein with DNA binding capabilities. The occurance of CREBL2 deletion in malignancy suggests that CREBL2 may act as a tumor suppressor gene.
Abuse of opiates, including morphine, induced remarkable synaptic adaptation in several brain regions including ventral tegmental area (VTA), which underlay the induction and maintenance of opioid dependence and addiction. Scaffolding protein postsynaptic density protein 95 (PSD-95) is critically involved in the glutamatergic synaptic maturation and plasticity in the central neurons. The present study revealed a significantly increased mRNA and protein expression of PSD-95 in the VTA of the rats conditioned with morphine. The further chromatin immunoprecipitation study found an increased histone H3 acetylation in the promoter region of Dlg4. An upregulation of expression of phosphorylated cAMP response element-binding protein (pCREB) and the occupancy of pCREB in the Dlg4 promoter region were shown in the VTA of the morphine-conditioned rats. Inhibition of pCREB activity significantly decreased the histone H3 acetylation in Dlg4 promoter region, PSD-95 upregulation, enhancement of glutamatergic strength
Fasting elicits transcriptional programs in hepatocytes leading to glucose and ketone production. This transcriptional program is regulated by many transcription factors (TFs). To understands how this complex network regulates the metabolic response to fasting we aimed at isolating the enhancers and TFs dictating it. Measuring chromatin accessibility revealed that fasting massively reorganizes liver chromatin, exposing numerous fasting-induced enhancers. By utilizing computational methods in combination with dissecting enhancers features and TF cistromes, we implicated four key TFs regulating the fasting response: glucocorticoid receptor (GR), cAMP responsive element binding protein 1 (CREB1), peroxisome proliferator activated receptor alpha (PPARA) and CCAAT/enhancer binding protein beta (CEBPB). These TFs regulate fuel production by two distinctly-operating modules, each controlling a separate metabolic pathway. The gluconeogenic module operates through assisted loading whereby GR doubles the ...
CREB3L1 antibody [C3], C-term (cAMP responsive element binding protein 3-like 1) for WB. Anti-CREB3L1 pAb (GTX104818) is tested in Human samples. 100% Ab-Assurance.
Early odor preference learning in rats is associated with increases of phosphorylated CREB (pCREB) in mitral cells of the olfactory bulb. In the present study, herpes simplex virus expressing CREB (HSV-CREB) and dominant-negative mutant CREB (HSV-mCREB) have been injected into the bulb to assess a causal role for CREB and pCREB in this model. Odor paired with stroking or with the β-adrenoceptor agonist isoproterenol produces odor approach 24 hr later. Isoproterenol-induced learning exhibits an inverted U curve dose-dependent learning relationship with both low and high doses failing to produce learning. pCREB increases have only been seen at the learning effective dose. In the present study, injection of an HSV vector expressing mutant CREB into the olfactory bulb prevented learning induced by stroking. Control HSV expressing LacZ was without effect. Expression of mutant CREB shifted the dose-learning curve for isoproterenol to the right such that a higher dose was required to induce learning. ...
Incubation of 3T3-L1 preadipocytes with isobutylmethylxanthine (IBMX), dexamethasone, and insulin, alone or in combination, demonstrated that IBMX, which increased cAMP-response element-binding protein (CREB) phosphorylation, was the predominant regulator of Pde3b expression. Real time PCR and immunoblotting indicated that in 3T3-L1 preadipocytes, IBMX-stimulated induction of Pde3b mRNA and protein was markedly inhibited by dominant-negative CREB proteins. By transfecting preadipocytes, differentiating preadipocytes, and HEK293A cells with luciferase reporter vectors containing different fragments of the 5- flanking region of the Pde3b gene, we identified a distal promoter that contained canonical cis-acting cAMP-response elements (CRE) and a proximal, GC-rich promoter region, which contained atypical CRE. Mutation of the CRE sequences dramatically reduced distal promoter activity; H89 inhibited IBMX-stimulated CREB phosphorylation and proximal and distal promoter activities. Distal promoter ...
The concentration of glucose in the bloodstream is regulated by glucose itself, along with the hormones insulin and glucagon. Glucagon stimulates gluconeogenesis in part by regulating phosphorylation of a transcriptional coactivator known as cyclic adenosine monophosphate response element-binding protein 2 (CRTC2). Dentin et al. (see the Perspective by Birnbaum) found that high concentrations of circulating glucose also regulate CRTC2, but do so through stimulation of the hexosamine biosynthetic pathway and consequent O-linked glycosylation of the same serine residue in CRTC2 that is modified by phosphorylation. Thus, CRTC2 integrates signals from hormones and nutrients and might be a target for efforts to treat abnormalities of glucose homeostasis that are associated with diabetes.. R. Dentin, S. Hedrick, J. Xie, J. Yates, III, M. Montminy, Hepatic glucose sensing via the CREB coactivator CRTC2. Science 319, 1402-1405 (2008). [Abstract] [Full Text]. M. J. Birnbaum, Sweet conundrum. Science 319, ...
4-PPBP is a molecule which binds to sigma receptors.[1] 4-PPBP decreases neuronal nitric oxide synthase (nNOS) activity and ischemia-evoked nitric oxide (NO) production. 4-PPBP provides neuroprotection; this involves the prevention of ischemia-induced intracellular Ca2+dysregulation.[2]4-PPBP protects neurons using a mechanism that activates the transcription factor cyclic adenosine monophosphate response element-binding protein (CREB). Neuroprotection that is associated with 4-PPBP increases Bcl-2 expression; Bcl-2 expression is regulated by CREB. [3] ...
Next, we focused on intermediate signaling molecules that are implicated in the mediation of cell motility and calcium signaling. Compared with control cells, MECs treated with recMFAP5 had higher expression of phosphorylated FAK (p-FAK) (Y861), p-PLC-γ1 (Y783), p-PKCθ (T538), p-ERK1/2 (T202/Y204), phosphorylated myosin regulatory light chain 2 (p-MLC2) (T18/S19), phosphorylated cyclic AMP-responsive element-binding protein (p-CREB) (S133), c-Jun, and p-c-Jun (S73), which may have led to the upregulation of LPP expression and thus increased cell motility and permeability (Figure 7G).. Because our data demonstrated that MFAP5-induced microvascular endothelial cell motility was suppressed in cells that had been pretreated with an anti-αVβ3 integrin antibody (Figure 7H) and that MFAP5-upregulated p-FAK (Y861) expression was suppressed in cells that had been pretreated with BAPTA-AM (1,2-bis-[2-aminophenoxy]-ethane-N,N,N′,N′-tetraacetic acid, tetraacetoxymethyl ester) (Supplemental Figure 9A ...
Rabbit anti CREB1 antibody recognizes cyclic AMP-responsive element-binding protein 1 (CREB1). CREB1 is a transcription factor that has be
Defective heme synthesis in mammals has been suspected of causing neuropathy associated with porphyrias and lead poisoning. To determine the molecular action of heme in neuronal cells, we examined the effect of the inhibition of heme synthesis on nerve growth factor (NGF) signaling in PC12 cells. We found that the inhibition of heme synthesis by succinyl acetone interferes with NGF-induced neurite outgrowth in PC12 cells. Furthermore, we show that heme deficiency obliterates the activation of the signaling intermediates of the Ras-mitogen-activated protein kinase signaling pathway and its downstream target, the transcription activator cyclic AMP response element-binding protein. Strikingly, microarray expression analysis shows that the inhibition of heme synthesis selectively diminishes the induction of expression of a subset of neuron-specific genes by NGF, such as Ras and neurofilament proteins, whereas NGF induces the expression of several major classes of neuronal genes that encode ...
Our hypothesis is based on several lines of evidence. First, the effects of cAMP and DA on both 4xCRE (Figs. 3a,b, 5) and c-fos and BDNF mRNA expression (Fig. 6) are blocked by NMDAR antagonists. Second, two structurally distinct inhibitors of neuronal EAA uptake, TBOA (Fig. 7) and trans-PDC (supplemental Fig. S3, available at www.jneurosci.org as supplemental material), potentiated the stimulation of gene transcription by cAMP. Third, the aspartate+glutamate-, but not the glutamate-only-, scavenging system abolished stimulation of CREB-dependent gene transcription by forskolin (Fig. 8); the aspartate-scavenging enzyme, GOT, degrades l- but not d-aspartate demonstrating that l-aspartate is the active extracellular EAA in this signaling pathway. Finally, forskolin was found to induce release of aspartate but not glutamate (Fig. 9). Together, these results lead to the conclusion that cAMP-induced release of aspartate and the resulting activation of NR2B-containing NMDARs mediate the effects of ...
In type 2 diabetes, chronic hyperglycemia is detrimental to beta-cells, causing apoptosis and impaired insulin secretion. The transcription factor cAMP-responsive element-binding protein (CREB) is crucial for beta-cell survival and function. We inves
CG-001 is a selective Wnt/β-catenin signalling inhibitor with an IC50 of 3μM. ICG 001, a small molecule that down-regulates beta-catenin/T cell factor signaling by specifically binding to cyclic AMP response element-binding protein. ICG001 selectively ind
RefSeq Summary (NM_001675): This gene encodes a transcription factor that was originally identified as a widely expressed mammalian DNA binding protein that could bind a tax-responsive enhancer element in the LTR of HTLV-1. The encoded protein was also isolated and characterized as the cAMP-response element binding protein 2 (CREB-2). The protein encoded by this gene belongs to a family of DNA-binding proteins that includes the AP-1 family of transcription factors, cAMP-response element binding proteins (CREBs) and CREB-like proteins. These transcription factors share a leucine zipper region that is involved in protein-protein interactions, located C-terminal to a stretch of basic amino acids that functions as a DNA binding domain. Two alternative transcripts encoding the same protein have been described. Two pseudogenes are located on the X chromosome at q28 in a region containing a large inverted duplication. [provided by RefSeq, Sep 2011 ...
Alzheimers disease (AD) is a progressive neurodegenerative disease and the most common form of senile dementia. Recently, scientists have put significant effort into exploring the molecular mechanisms involved in the pathological processes leading to the disease. A vast number of studies have focused on understanding the nitric oxide (NO) signaling pathway, which culminates with the phosphorylation of the transcription factor cAMP-responsive element-binding protein (CREB) through the increase of the second messenger cyclic guanosine monophosphate (cGMP) and activation of cGMP-dependent protein kinase. This book chapter provides an overview of the progress being made in modulating the hippocampal synaptic transmissions, which are critical for learning and memory, by targeting the different components of the NO/cGMP/CREB phosphorylation signaling pathway. Furthermore, a description of recent research on this pathway through the use of phosphodiesterase inhibitors is emphasized.
Colorectal cancer (CRC) is the third leading cause of cancer-related death in the United States. During the tumorigenesis and metastasis of CRC, cells encounter numerous cellular and molecular events. ATF3, a member of the ATF/CREB transcription factor family, plays an important role on regulation of apoptosis and is regarded as a potential molecular target for chemoprevention and chemotherapy of colon cancer. The current study was performed to investigate cellular and molecular mechanisms by which ATF3 affects colon cancer-related phenotypes including apoptosis and metastasis. Here, we demonstrated that knockdown of ATF3 using small interfering RNA (siRNA) promotes the expression of anti-apoptotic protein, B-cell lymphoma 2 (Bcl-2), in colon cancer cells, while overexpression of ATF3 resulted in a dramatic decrease in Bcl-2 protein. Gain of function of ATF3 in colon cancer cell line HCT116 led to an increase of pro-apoptotic protein Bcl-2 homologous antagonist killer (Bak), followed by the ...
We previously demonstrated that APP epigenetically regulates Egr1 expression both in cultured neurons and in vivo. Since Egr1 is an immediate early gene involved in memory formation, we wondered whether other early genes involved in memory were regulated by APP and we studied molecular mechanisms involved. By comparing prefrontal (PF) cortex from wild type (APP+/+) and APP knockout mice (APP-/-), we observed that APP down regulates expression of four immediate early genes, Egr1, c-Fos, Bdnf and Arc. Down regulation of Egr1, c-Fos and Bdnf transcription resulted from a decreased enrichment of acetylated histone H4 on the corresponding gene promoter. Further characterization of H4 acetylation at Egr1 and c-Fos promoters revealed increased acetylation of H4K5 and H4K12 residues in APP-/- mice. Whereas APP affected Egr1 promoter activity by reducing access of the CREB transcription factor, its effect on c-Fos appeared to depend on increased recruitment of HDAC2 histone deacetylase to the gene ...
TY - JOUR. T1 - Interplay of the E box, the cyclic AMP response element, and HTF4/HEB in transcriptional regulation of the neurospecific, neurotrophin-inducible vgf gene. AU - Di Rocco, Giuliana. AU - Pennuto, Maria. AU - Illi, Barbara. AU - Canu, Nadia. AU - Filocamo, Gessica. AU - Trani, Eugenia. AU - Rinaldi, Anna Maria. AU - Possenti, Roberta. AU - Mandolesi, Georgia. AU - Sirinian, M. Isabella. AU - Jucker, Richard. AU - Levi, Andrea. AU - Nasi, Sergio. PY - 1997/3. Y1 - 1997/3. N2 - vgf is a neurotrophin response-specific, developmentally regulated gene that codes for a neurosecretory polypeptide. Its transcription in neuronal cells is selectively activated by the neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor, and neurotrophin 3, which induce survival and differentiation, and not by epidermal growth factor. We studied a short region of the rat vgf promoter which is essential for its regulated expression. A cyclic AMP response element (CRE) within this region is ...
article{955774, abstract = {Among the mitogen-activated protein kinase (MAPK) targets, MSKs (mitogen- and stress-activated protein kinases) comprise a particularly interesting protein family. Because MSKs can be activated by both extracellular-signal-regulated kinase and p38 MAPKs, they are activated by many physiological and pathological stimuli. About ten years after their original discovery, they have been recognized as versatile kinases regulating gene transcription at multiple levels. MSKs directly target transcription factors, such as cAMP-response-element-binding protein and nuclear factor-kappaB, thereby enhancing their transcriptional activity. They also induce histone phosphorylation, which is accompanied by chromatin relaxation and facilitated binding of additional regulatory proteins. Here, we review the current knowledge on MSK activation and its molecular targets, focusing on recent insights into the role of MSKs at multiple levels of transcriptional regulation.}, author = ...
In addition to these posttranslational changes, an alteration in the expression of effector molecules in the DRG (66) and dorsal horn (67-69) is a prominent feature of inflammation and can be initiated in two ways. The first is as a result of an activity-dependent activation of the CREB transcription factor both in DRG and dorsal horn neurons (ref. 70; Fig. 3). As discussed above, this will result, after a delay of several hours for transcription and translation in the DRG and protein transport to central terminals, in a potentiated system in which the C fibers are primed to exert a greater effect on dorsal horn neurons as a result of an increased expression of neuromodulators like BDNF. In addition, the dorsal horn is simultaneously made hyperresponsive to such neuromodulators as a result of an activity-dependent increased expression of the TrkB receptor. The second way that transcriptional changes occur after inflammation is via the production in the inflamed tissue of specific signal ...
negative regulation of gene expression / positive regulation of CREB transcription factor activity / G-protein coupled receptor signaling pathway / regulation of sensory perception of pain / protein import into nucleus, translocation / phospholipase C-activating G-protein coupled receptor signaling pathway / cellular response to growth factor stimulus / immune response / adult locomotory behavior / G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / neuropeptide signaling pathway / adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway / synaptic transmission / regulation of calcium ion transport / cellular response to toxic substance / eating behavior / cellular response to hypoxia / negative regulation of protein oligomerization / positive regulation of peptidyl-serine phosphorylation / regulation of mitochondrial membrane potential / opioid receptor signaling pathway ...
Extensive evidence implicates CREB-dependent gene transcription in memory (Bourtchuladze et al., 1994; Yin et al., 1994; Guzowski and McGaugh, 1997; Bartsch et al., 1998; Kida et al., 2002; Pittenger et al., 2002; Frankland et al., 2004). Multiple signaling pathways phosphorylate CREB at Ser133 (Shaywitz and Greenberg, 1999; Mayr and Montminy, 2001; Lonze and Ginty, 2002), which stimulates the recruitment of coactivators CBP/p300 (Chrivia et al., 1993; Parker et al., 1996). However, this phosphorylation event is not always sufficient to activate transcription (Impey et al., 1996; Mayr and Montminy, 2001) suggesting that CREB-mediated transcription is regulated by additional mechanisms.. In 2003, two laboratories identified a new family of CREB-specific coactivators, now referred to as CRTCs (Iourgenko et al., 2003; Conkright et al., 2003b). CRTC is thought to enhance transcription by facilitating the interaction of CREB with the RNA polymerase II pre-initiation complex (Conkright et al., 2003b; ...
TY - JOUR. T1 - Epistatic interaction of CREB1 and KCNJ6 on rumination and negative emotionality. AU - Lazary, Judit. AU - Juhasz, Gabriella. AU - Anderson, Ian M.. AU - Jacob, Christian P.. AU - Nguyen, T. Trang. AU - Lesch, Klaus Peter. AU - Reif, Andreas. AU - Deakin, J. F.William. AU - Bagdy, Gyorgy. PY - 2011/1/1. Y1 - 2011/1/1. N2 - G protein-activated K+ channel 2 (GIRK2) and cAMP-response element binding protein (CREB1) are involved in synaptic plasticity and their genes have been implicated depression and memory processing. Excessive rumination is a core cognitive feature of depression which is also present in remission. High scores on the Ruminative Response Scale (RRS) questionnaire are predictive of relapse and recurrence. Since rumination involves memory, we tested the hypothesis that variation in the genes encoding GIRK2 (KCNJ6) and CREB1 mechanisms would influence RRS scores. GIRK2 and CREB1 polymorphisms were studied in two independent samples (n = 651 and n = 1174) from the ...
The cellular transcription factor CREB (cAMP response element-binding protein) helps learning and the stabilization and retrieval of fear-based, long-term memories. This is done mainly through its expression in the hippocampus and the amygdala. Studies supporting the role of CREB in cognition include those that knock out the gene, reduce its expression, or overexpress it. Research suggests that CREB has a role in the molecular steps that stabilize memory in the brain, including that of emotional memory. Evidence of CREBs role in emotional memory falls into three experimental categories: negative manipulations (where the levels of CREB were lowered), positive manipulations (where the levels of CREB were increased), and non-interventions (where the endogenous levels of CREB were tracked before and after learning). Knockout studies in Aplysia sea slugs indicated that decreasing CREB function blocks long-term changes in synaptic function, but not short-term ones. Changes in synaptic function (i.e., ...
Many human and murine tumors of distinct histology and cells of the tumor microenvironment show increased CREB expression and activity when compared with adjacent nonmalignant tissue (4), which is even more enhanced in metastasis suggesting a role for CREB in the initiation, maintenance, and progression of tumors (33, 34). This is often accompanied by poor prognosis and decreased survival rates of patients with tumor (35). Although CREB dysregulation is a critical factor in cancer development and progression, the underlying molecular mechanisms that lead to its overexpression have not yet been determined in detail. One approach to unravel this process is to determine the link(s) between oncogene expression and CREB using an in vitro model of oncogene-mediated transformation, as well as human tumor lesions with known HER-2/neu status. As shown in Fig. 7F, an important role for HER-2/neu was suggested for CREB expression and activity both in vitro and in vivo. This is based on the data ...
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ObjectiveGlucagon-like peptide-1 (GLP-1) plays a major role in pancreatic β-cell function and survival by increasing cytoplasmic cAMP levels, which are thought to affect transcription through activation of the basic leucine zipper (bZIP) transcription factor CREB. Here, we test CREB function in the adult β-cell through inducible gene deletion.MethodsWe employed cell type-specific and inducible gene ablation to determine CREB function in pancreatic β-cells in mice.ResultsBy ablating CREB acutely in mature β-cells in tamoxifen-treated CrebloxP/loxP;Pdx1-CreERT2 mice, we show that CREB has little impact on β-cell turnover, in contrast to what had been postulated previously. Rather, CREB is required for GLP-1 to elicit its full effects on stimulating glucose-induced insulin secretion and protection from cytokine-induced apoptosis. Mechanistically, we find that CREB regulates expression of the pro-apoptotic gene p21 (Cdkn1a) in β-cells, thus demonstrating that CREB is essential to mediating ...
TY - JOUR. T1 - CREB activation in the rapid, intermediate, and delayed ischemic preconditioning against hypoxic-ischemia in neonatal rat. AU - Lin, Wan Ying. AU - Chang, Ying Chao. AU - Lee, Hsueh Te. AU - Huang, Chao Ching. PY - 2009/2. Y1 - 2009/2. N2 - Ischemic preconditioning (IP) is a defense program in which exposure to sublethal ischemia followed by a period of reperfusion results in subsequent resistance to severe ischemic insults. Very few in vivo IP models have been established for neonatal brain. We examined whether rapid, intermediate, and delayed IP against hypoxic-ischemia (HI) could be induced in neonatal brain, and if so, whether the IP involved phosphorylation of cAMP response element-binding protein (pCREB) after HI. Postnatal day 7 rat pups were subjected to HI at 2 h (2-h IP), 6 h (6-h IP), or 22 h (22-h IP) after IP. We found all three IP groups had significantly reduced neuronal damage and TUNEL-(+) cells 24 h post-HI than no-IP group. Compared with control, the no-IP ...
The mechanism of memory storage has been extensively studied, especially in the hippocampus and amygdala, however, we know very little about how specific population of neurons in these brain areas are selectively recruited as part of the memory storage cells. This phase of memory formation is referred to as memory allocation. Recent findings suggest that that cAMP response element binding protein (CREB) is involved in the mechanism of memory allocation in amygdala. While we have found the mechanisms of fear memory allocation in the amygdala, we do not know how allocation works in other brain areas. This research focuses on understanding the mechanism of memory allocation in the sensory cortex, where properties of cellular and circuit organization are different from the amygdala. We hypothesized that specific population of neurons is selectively recruited as memory cells and CREB is involved in this mechanisms. To address this hypothesis, we have developed lentivirus to express CREB and hM4Di ...
Ca2+ release induced by depolarization of skeletal muscle cells can be separated into two independent components; the fast Ca2+ transient, homogenously distributed through the cell that corresponds to excitation-contraction coupling, and the slow Ca2+ transient, with a distinct nuclear component, generated by IP3 (Jaimovich et al., 2000). Slow Ca2+ signals with similar characteristics, although displaying particular kinetics can also be elicited by androgens like testosterone (Estrada et al., 2000; Estrada et al., 2003), or hormones such as insulin-like growth factor (Espinosa et al., 2004). Slow Ca2+ signals have been shown to participate in phosphorylation of both MAP kinases ERK 1 and 2, and transcription factor CREB, as well as in the expression of early genes fos, jun and egr-1 (Powell et al., 2001; Carrasco et al., 2003). In this work, we determined that type 1 and 3 IP3Rs are expressed and are functional in myonuclei, mediating nucleoplasmic Ca2+ changes, which in turn induce CREB ...
Co-localization of p-CREB and GFAP in coronal brain sections of ACC. Photomicrographs showed the expression of p-CREB (red) and GFAP (an astrocytic marker, gree
View Notes - 2010 Bio 317 Lecture 24 from BIO 317 at SUNY Stony Brook. 12/1/10 CREB on CRE Alphahelix LeucineZipper MG2+ Attenuation Due to S/T Phosphatase PP-1 PassiveDiffusion 1 12/1/10 CBP -
The general public might think that this is only possible in the movie or in the distant future (Y 2084). However, in reality, a research team led by professor Jin-Hee Han at KAIST reported that a substance or chemical can be injected into the mouse brain to induce recall artificially or make modifications of specific memory in the absence of any behavioural cues (Kim et al., Nature Neuroscience 2014). It has been reported that neurons with higher level of CREB than their neighbours (CREB = cAMP/Ca2+ response element binding protein) are selected to be included into memory engram during memory formation. Inspired by this finding, the CREB gene was injected into small number of cells in the mouse amygdala, a brain area responsible for fear. Surprisingly, simply injecting the drug that stimulated only CREB cells was sufficient to activate recall of that learned memory. Moreover, the same procedure was also able to modify the established memory. This was laboratory work carried out by the leading ...
Maio M, Bertocci E, Pilla L, Fazio C, Chiarucci C, Cutaia O, Fonsatti E, Maccalli C, Parmiani G; NIBIT. (Seliger B). Cancer Bio-Immunotherapy in Siena: Twelfth Meeting of the Network Italiano per la Bioterapia dei Tumori (NIBIT), Siena, Italy, October 9-11, 2014. Cancer Immunol Immunother. 2016 Jan;65(1):119-26. Rothe K, Quandt D, Schubert K, Rossol M, Klingner M, Jasinski-Bergner S, Scholz R, Seliger B, Pierer M, Baerwald C, Wagner U. Latent Cytomegalovirus Infection in Rheumatoid Arthritis and Increased Frequencies of Cytolytic LIR-1+CD8+ T Cells. Arthritis Rheumatol. 2016 Feb;68(2):337-46. Lennicke C, Rahn J, Heimer N, Lichtenfels R, Wessjohann LA, Seliger B. Redox proteomics: Methods for the identification and enrichment of redox-modified proteins and their applications. Proteomics. 2016 Jan;16(2):197-213. Steven A, Seliger B. Control of CREB expression in tumors: from molecular mechanisms and signal transduction pathways to therapeutic target. Oncotarget. 2016 Jun 7;7(23):35454-65. ...