Histone lysine acetylation is central to epigenetic control of gene transcription. Bromodomains of chromosomal proteins function as acetyl-lysine (Kac) binding domains. However, how bromodomains recognize site-specific histones remains unanswered. Here, we report three three-dimensional solution structures of the bromodomains of the human transcriptional coactivators CREB-binding protein (CBP) and p300/CBP-associated factor (PCAF) bound to peptides derived from histone acetylation sites at lysines 36 and 9 in H3, and lysine 20 in H4. From structural and biochemical binding analyses, we determine consensus histone recognition by the bromodomains of PCAF and CBP, which represent two different subgroups of the bromodomain family. Through bromodomain residues in the ZA and BC loops, PCAF prefers acetylation sites with a hydrophobic residue at (Kac+2) position and a positively charged or aromatic residue at (Kac+3), whereas CBP favors bulky hydrophobic residues at (Kac+1) and (Kac+2), a positively ...
Members of the CREB-binding protein/p300-interacting transactivator with ED-rich tail (CITED) family bind CREB-binding protein and p300 with high affinity and regulate gene transcription. Gene knockout studies indicate that CITED2 is required for neural crest and neural tube development and that it functions as a co-activator for transcription factor AP-2 (TFAP2). Here we describe human CITED4, a new member of this family, which is encoded by a single exon mapping to chromosome 1p34--1p35. CITED4 and p300/CREB-binding protein are present in endogenous naturally occurring complexes, indicating that they interact physiologically. The interaction occurs between the cysteine-histidine-rich domain 1 of p300 and the carboxyl terminus of CITED4. In keeping with this, CITED4 functions as a transactivator when artificially targeted to a promoter element. CITED4 physically interacts with all TFAP2 isoforms in vitro and strongly co-activates all TFAP2 isoforms in Hep3B cells. Co-activation of TFAP2 requires amino
Mier1 encodes a novel transcriptional regulator and was originally isolated as a fibroblast growth factor early response gene. Two major protein isoforms have been identified, MIER1α and β, which differ in their C-terminal sequence. Previously, we demonstrated that both isoforms recruit histone deacetylase 1 (HDAC1) to repress transcription. To further explore the role of MIER1 in chromatin remodeling, we investigated the functional interaction of MIER1 with the histone acetyltransferase (HAT), Creb-binding protein (CBP). Using GST pull-down assays, we demonstrate that MIER1 interacts with CBP and that this interaction involves the N-terminal half (amino acids 1-283) of MIER1, which includes the acidic activation and ELM2 domains and the C-terminal half (amino acids 1094-2441) of CBP, which includes the bromo-, HAT, C/H3 and glutamine-rich domains. Functional analysis, using HEK293 cells, shows that the CBP bound to MIER1 in vivo has no detectable HAT activity. Histone 4 peptide binding assays
Avots, A., Buttmann, M., Chupvilo, S., Escher, C., Smola, U., Bannister, A.J., Rapp, U.R., Kouzarides, T., Serfling, E. CBP/p300 integrates Raf/Rac-signalling pathways in the transcriptional induction of NF-Atc during T cell activation Immunity 10: 515-524 (1999) Chirmule, N., Avots, A., LakshmiTamma, S.M., Pahwa, S., Serfling, E. CD4-mediated signals induce T cell dysfunction in vivo J. Immunol. 163: 644-649 (1999) Bannert, N., Avots, A., Baier, M., Serfling, E., Kurth, R. GA-binding protein factors, in concert with the coactivator CREB binding protein/p300, control the induction of the interleukin 16 promoter in T lymphocytes Proc. Natl. Acad. Sci. USA 96: 1541-1546 (1999) Chupvilo, S., Zimmer, M., Kerstan, A., Glöckner, J., Avots, A., Escher, C., Fischer, C., Inashkina, I., Jankevics, E., Berberich-Siebelt, F., Schmitt, E., Serfling, E. Alternative polyadenylation events contribute to the induction of NF-ATc in effector T cells Immunity 10: 261-269 (1999) Chupvilo, S., Avots, A., ...
Following the publication of this article [1], the authors found that the primers listed for CREB-binding protein were not correct. This mistake occurred during assembly of the primer table and the authors apologize for this error. This correction does not change the data included in the paper, their interpretation nor the conclusions drawn.
In the present study, we sought to examine the molecular basis for the differential regulation of several members of the IFN-α/β gene family (IFNA and IFNB) by IRF-3 and IRF-7. The IFNB, IFNA1, IFNA2, and RANTES promoters were activated by coexpression of either IRF-3 or IRF-7, whereas the IFNA4, IFNA7, and IFNA14 promoters were exclusively activated by IRF-7 and not by IRF-3. Analysis of protein-DNA interactions revealed that recombinant IRF-3 and IRF-7 selectively bound to different regions of the IFNB promoter; IRF-3 bound preferentially to the PRDIII domain of the IFNB promoter, while IRF-7 interacted exclusively with the PRDI domain. PCR-mediated DNA binding site selection results demonstrated that IRF-3 recognized the IRF consensus element 5′-GAAANNGAAANN-3′. Replacement of a single nucleotide within the GAAA core half-site was sufficient to preclude IRF-3 DNA binding. IRF-7 bound to a related sequence motif but with greater flexibility than IRF-3; a single nucleotide replacement did ...
The major finding in this study is that ethanol induces an increase in gene expression via CREB and PKA. This increase in gene expression requires both PKA and CREB phosphorylation. Although we had previously shown that exposure to ethanol resulted in phosphorylation of CREB in NG108-15 cells, there is accumulating evidence that CREB phosphorylation is not sufficient to regulate gene expression under the control of CREs; activation of the coactivator CREB-binding protein (CBP) and other downstream elements is also required for increases in CRE-mediated gene expression (Montminy, 1997; Cardinaux et al., 2000).Thibault et al. (2000) have reported increases in genes the expression of which is known to be cAMP-dependent. However, ethanol activates many different signal transduction pathways in addition to PKA (Diamond and Gordon, 1997), and most genes have regulatory elements activated or inhibited by all of these pathways. Therefore, the experiments presented here are the first demonstration that ...
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
We also aim to understand the structure-function relationship of very large ("oversized") proteins, practically neglected from a structural point of view thus far. Structural biology has traditionally addressed the structure of small folded proteins, whereas the field of structural disorder has focused on either fully disordered proteins/regions or short disordered elements that undergo induced folding in the presence of their partner. Here we would like to probe into the structure of the very large transcriptional co-activator CREB-binding protein (CBP), by addressing its structure by means traditionally applied in the case of protein complexes. CBP has about seven domains and disordered linker regions connecting them, the topology of which will be outlined by a combination of high-resolution (NMR, X-ray) and low-resolution (MS, EM, AFM) techniques ...
Cancer, Epidermal Growth Factor, Gene, Growth, Survival, Cell Line, Tumors, Disease, Kinase, Mutation, Patient, Phenotype, Cell, Insulin, Mouse, Acetylation, Binding Protein, Creb-binding Protein, Neuroblastoma, Nuclear Export
Function: Recruited and tyrosine phosphorylated by several receptor systems, for example the T-cell, leptin and insulin receptors. Once phosphorylated, functions as an adapter protein in signal transduction cascades by binding to SH2 and SH3 domain- containing proteins. Role in G2-M progression in the cell cycle. Represses CBP-dependent transcriptional activation apparently by competing with other nuclear factors for binding to CBP. Also acts as a putative regulator of mRNA stability and/or translation rates and mediates mRNA nuclear export. Isoform 3, which is expressed in growth-arrested cells only, inhibits S phase ...
It does not matter how the diet is restricted. It can be in terms of carbohydrates,fats or proetins. What matters is the diet should be of low calorie. This brings about a change in the CBP proteins that control the genes related to cellular functions ...
The inappropriate sustained SNA increase in OSA patients likely contributes to hypertension, organ damage, and mortality; however, it is unclear how excessive SNA develops in these patients. Several factors, including obesity and increased carotid body chemoreceptor sensitivity due to intermittent hypoxia, have been considered. Obesity could mechanically obstruct the airway and increase SNA through leptin, insulin, angiotensin, and cytokine actions; however, many OSA patients are not obese (23). Carotid body hypersensitivity as a result of intermittent hypoxia has been confirmed in animal models of OSA. In fact, plasticity of the carotid body glomus cells with long-term sensory facilitation and sensitization have been reported (18, 24) and associated with ROS and NOX2-dependent accumulation of HIF1 and the transcriptional coactivator CREB-binding protein (25). Central neuroplasticity. A provocative possibility for OSA-associated SNA dysfunction is that excessive activation of CNS nuclei induces ...
Rubinstein-Taybi syndrome (RSTS) is an uncommon genetic disorder characterised by a typical facies, small stature, broad angulated thumbs and intellectual impairment. Dental changes are a minor, yet significant component of the condition. Craniofacial growth retardation in RSTS is frequently complicated by unerupted teeth, while dental caries is related to the inherent intellectual deficit. Dental problems necessitate interdisciplinary management in terms of oral surgery, conservative dentistry, periodontics and orthodontics. When affected individuals are unco-operative, certain dental procedures may warrant general anaesthesia. In these instances, dental and medical staff will combine their expertise to enhance the well-being of the patient. In addition, specific dental changes may alert the medical practitioner to the possible diagnosis of RSTS. In this article we document the oro-dental manifestations and review the oro-dental approach in the management of three patients with RSTS. Our experience in
Rubinstein, J. "Broad thumb-hallux (Rubinstein-Taybi) Syndrome 1957-1988". Am J Med Gen Suppl . vol. 6. 1990. pp. 3-16. (An early review of 571 cases, this article provides a detailed description of the physical findings in this syndrome.). Wiley, S, Swayne, S, Rubinstein, J, Lanphear, N, Stevens, C. "Rubinstein-Taybi syndrome medical guidelines". Am J Med Genet. vol. 119A. 2003. pp. 101-110. (This article includes specific surveillance and intervention recommendations compiled by a group of pediatric experts.). Cantani, A, Gagliesi, D. "Rubinstein-Taybi syndrome. Review of 732 cases and analysis of typical traits". Eur Rev Med Pharmacol Sci. vol. 2. 1998. pp. 81-87. (This is an analysis of 732 cases and provides a summary of the physical findings of the syndrome and discusses epidemiology and genetics known at the time of publication.). Roelfsema, J, Peters, D. "Rubinstein-Taybi syndrome: clinical and molecular overview". Expert Rev Mol Med. vol. 9. 2007. pp. 1-15. (This article details the ...
Mutations in the coactivator CREB-binding protein (CBP) are a major cause of the human skeletal dysplasia Rubinstein-Taybi syndrome (RTS); however, the mechanism by which these mutations affect skeletal mineralization and patterning is unknown. Here, we report the identification of 3-phosphoinositide-dependent kinase 1 (PDK1) as a key regulator of CBP activity and demonstrate that its functions map to both osteoprogenitor cells and mature osteoblasts. In osteoblasts, PDK1 activated the CREB/CBP complex, which in turn controlled runt-related transcription factor 2 (RUNX2) activation and expression of bone morphogenetic protein 2 (BMP2). These pathways also operated in vivo, as evidenced by recapitulation of RTS spectrum phenotypes with osteoblast-specific Pdk1 deletion in mice (Pdk1osx mice) and by the genetic interactions observed in mice heterozygous for both osteoblast-specific Pdk1 deletion and either Runx2 or Creb deletion. Finally, treatment of Pdk1osx and Cbp+/- embryos with BMPs in utero ...
hypothetical protein, A306_06942, Anapl_13162, AS27_07110, CBP, CBP/p300, CREB-binding protein, CREB binding protein (Rubinstein-Taybi syndrome), crebbp-a, crebbp-b, D623_10028045, E1A binding protein p300, EP300, H920_13788, hmm291030, KAT3A, M91_18874, MDA_GLEAN10009599, N301_13283, N302_12939, N303_04372, N307_13277, N308_10632, N309_02966, N311_11763, N312_01973, N321_00697, N326_12400, N327_01513, N332_08465, N334_05471, N335_14336, N336_02992, N339_02947, p300, p300/CBP, PAL_GLEAN10011621, RSTS, RTS, UY3_13419, Y1Q_016907, Z169_09090, crebbp ...
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, ...
Hop on to get the meaning of p/ CIP acronym / slang / Abbreviation. The Medical & Science Acronym / Slang p/ CIP means... AcronymsAndSlang. The p/ CIP acronym/abbreviation definition. The p/ CIP meaning is p300/ CREB-binding protein (CBP)-interacting protein. The definition of p/ CIP by AcronymAndSlang.com
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 ...
CREBBP is targeted by inactivating mutations in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Here, we provide evidence from transgenic mouse models that Crebbp deletion results in deficits in B-cell development and can cooperate with Bcl2 overexpression to promote B-cell lymphoma. Through transcriptional and epigenetic profiling of these B cells, we found that Crebbp inactivation was associated with broad transcriptional alterations, but no changes in the patterns of histone acetylation at the proximal regulatory regions of these genes. However, B cells with Crebbp inactivation showed high expression of Myc and patterns of altered histone acetylation that were localized to intragenic regions, enriched for Myc DNA binding motifs, and showed Myc binding. Through the analysis of CREBBP mutations from a large cohort of primary human FL and DLBCL, we show a significant difference in the spectrum of CREBBP mutations in these 2 diseases, with higher frequencies of ...
The CREBBP gene is associated with autosomal dominant Rubinstein-Taybi syndrome 1 (RSTS1) (MedGen UID: 48517) and is commonly deleted in the recurrent 16p13.3 microdeletion syndrome (OMIM: 610543), a severe form of RSTS resulting from a contiguous gene deletion involving CREBBP as well as other neighboring genes.
In 1963, Rubinstein and Taybi first described a malformation syndrome characterized by distinctive facies, mental retardation, broad thumbs, and broad great toes as are seen in the images below. {file44122}{file44123}{file44124}Deletions in band 16p13 have been described in association with this disorder, and mutations in the cyclic adenosin...
CREBBP - CREBBP (Myc-DDK-tagged)-Human CREB binding protein (CREBBP), transcript variant 1 available for purchase from OriGene - Your Gene Company.
Sigma-Aldrich offers abstracts and full-text articles by [Q Li, H Peng, H Fan, X Zou, Q Liu, Y Zhang, H Xu, Y Chu, C Wang, K Ayyanathan, F J Rauscher, K Zhang, Z Hou].
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, ...
Lysine propionylation and butyrylation are protein modifications that were recently identified in histones. The molecular components involved in the two protein modification pathways are unknown, hindering further functional studies. Here we report identification of the first three in vivo non-histone protein substrates of lysine propionylation in eukaryotic cells: p53, p300, and CREB-binding protein. We used mass spectrometry to map lysine propionylation sites within these three proteins. We also identified the first two in vivo eukaryotic lysine propionyltransferases, p300 and CREB-binding protein, and the first eukaryotic depropionylase, Sirt1. p300 was able to perform autopropionylation on lysine residues in cells. Our results suggest that lysine propionylation, like lysine acetylation, is a dynamic and regulatory post-translational modification. Based on these observations, it appears that some enzymes are common to the lysine propionylation and lysine acetylation regulatory pathways. Our ...
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
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 ...
TY - JOUR. T1 - Chromatin-dependent cooperativity between constitutive and inducible activation domains in CREB. AU - Asahara, H.. AU - Santoso, B.. AU - Guzman, E.. AU - Du, K.. AU - Cole, P. A.. AU - Davidson, I.. AU - Montminy, M.. PY - 2001/11/22. Y1 - 2001/11/22. N2 - The cyclic AMP (cAMP)-responsive factor CREB induces target gene expression via constitutive (Q2) and inducible (KID, for kinase-inducible domain) activation domains that function synergistically in response to cellular signals. KID stimulates transcription via a phospho (Ser133)-dependent interaction with the coactivator paralogs CREB binding protein and p300, whereas Q2 recruits the TFIID complex via a direct association with hTAFII130. Here we investigate the mechanism underlying cooperativity between the Q2 domain and KID in CREB by in vitro transcription assay with naked DNA and chromatin templates containing the cAMP-responsive somatostatin promoter. The Q2 domain was highly active on a naked DNA template, and Ser133 ...
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; ...
The AlphaLISA SureFire Ultra p-CREB (Ser133) assay kit (High Volume) is an immunoassay for quantitative detection of phospho-CREB in cellular lysates.
I remember the fateful day when I saw my first Kix Commercial with its slogan Kid Tested, Mother Approved. In my ten-year-old mind, Id finally found the loophole in the cruel system of parental cereal control. Somehow, my mom actually obeyed this mantra. Kix occasionally landed in our cabinets, a brightly colored beacon in a sea of white and brown boxes. Recently, I bought a box to see if they were still as great as I remembered.
Looking for online definition of cAMP-responsive element-binding protein 3-like protein 4 in the Medical Dictionary? cAMP-responsive element-binding protein 3-like protein 4 explanation free. What is cAMP-responsive element-binding protein 3-like protein 4? Meaning of cAMP-responsive element-binding protein 3-like protein 4 medical term. What does cAMP-responsive element-binding protein 3-like protein 4 mean?
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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 - The transcriptional coactivator and acetyltransferase p300 in fibroblast biology and fibrosis. AU - Ghosh, Asish K.. AU - Varga, John. PY - 2007/12/1. Y1 - 2007/12/1. N2 - The transcriptional coactivator p300 is a ubiquitous nuclear phosphoprotein and transcriptional cofactor with intrinsic acetyltransferase activity. p300 controls the expression of numerous genes in cell-type and signal-specific manner, and plays a pivotal role in cellular proliferation, apoptosis, and embryogenesis. By catalyzing acetylation of histones and transcription factors, p300 plays a significant role in epigenetic regulation. Recent evidence suggests that abnormal p300 function is associated with deregulated target gene expression, and is implicated in inflammation, cancer, cardiac hypertrophy, and genetic disorders such as the Rubinstein-Taybi syndrome. The activity of p300 is regulated at multiple levels, including developmental stage-specific expression, post-translational modifications, subcellular ...
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] ...
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 ...
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 ...
Chromosomal translocations that fuse the mixed lineage leukemia (MLL) gene with multiple partners typify acute leukemias of infancy as well as therapy-related leukemias. We utilized a conditional knockin strategy to bypass the embryonic lethality caused by MLL-CBP expression and to assess the immediate effects of induced MLL-CBP expression on hematopoiesis. Within days of activating MLL-CBP, the fusion protein selectively expanded granulocyte/macrophage progenitors (GMP) and enhanced their self-renewal/proliferation. MLL-CBP altered the gene expression program of GMP, upregulating a subset of genes including Hox a9. Inhibition of Hox a9 expression by RNA interference demonstrated that MLL-CBP required Hox a9 for its enhanced cell expansion. Following exposure to sublethal γ-irradiation or N-ethyl-N-nitrosourea (ENU), MLL-CBP mice developed myelomonocytic hyperplasia and progressed to fatal myeloproliferative disorders. These represented the spectrum of therapy-induced acute myelomonocytic ...
Expression of CREBBP (CBP, KAT3A, RSTS, RTS) in cervix, uterine tissue. Antibody staining with HPA055861 and CAB004212 in immunohistochemistry.
Here, we present a structural and dynamic description of CBP-ID4 at atomic resolution. ID4 is the fourth intrinsically disordered linker of CREB-binding protein (CBP). In spite of the largely disordered nature of CBP-ID4, NMR chemical shifts and relaxation measurements show a significant degree of α-helix sampling in the protein regions encompassing residues 2-25 and 101-128 (1852-1875 and 1951-1978 in full-length CBP). Proline residues are uniformly distributed along the polypeptide, except for the two α-helical regions, indicating that they play an active role in modulating the structural features of this CBP fragment. The two helical regions are lacking known functional motifs, suggesting that they represent thus-far uncharacterized functional modules of CBP. This work provides insights into the functions of this protein linker that may exploit its plasticity to modulate the relative orientations of neighboring folded domains of CBP and fine-tune its interactions with a multitude of ...
Somatic mutations in CREBBP occur frequently in B-cell lymphoma. Here, we show that loss of CREBBP facilitates the development of germinal center (GC)-derived lymphomas in mice. In both human and murine lymphomas, CREBBP loss-of-function resulted in focal depletion of enhancer H3K27 acetylation and aberrant transcriptional silencing of genes that regulate B-cell signaling and immune responses, including class II MHC. Mechanistically, CREBBP-regulated enhancers are counter-regulated by the BCL6 transcriptional repressor in a complex with SMRT and HDAC3, which we found to bind extensively to MHC class II loci. HDAC3 loss-of-function rescued repression of these enhancers and corresponding genes, including MHC class II, and more profoundly suppressed CREBBP-mutant lymphomas in vitro and in vivo. Hence, CREBBP loss-of-function contributes to lymphomagenesis by enabling unopposed suppression of enhancers by BCL6/SMRT/HDAC3 complexes, suggesting HDAC3-targeted therapy as a precision approach for ...
The activation of the transcription factor NF-kB is central to the control of the cellular response triggered by many stimuli. Once released from the inhibitory molecule IkB, NF-kB is translocated to the nucleus, and it has to be phosphorylated to activate transcription. In protein kinase C (PKC)-deficient cells, NF-kB is transcriptionally inactive and the phosphorylation of the RelA subunit in response to tumor necrosis factor (TNF-alpha) is severely impaired. In vitro assays showed that PKC directly phosphorylates RelA. Here we demonstrate that Ser311 accounts for PKC phosphorylation of RelA and that this site is phosphorylated in vivo in response to TNF-alpha. Also, an inactivating mutation of that residue severely impairs RelA transcriptional activity, blocks its anti-apoptotic function and abrogates the interaction of RelA with the co-activator CBP as well as its recruitment, and that of RNA polymerase II (Pol II) with the interleukin-6 (IL-6) promoter. The interaction of endogenous CBP ...
Freds Dērsts piedzima Džeksonvilā, Floridā, ASV. Fredu audzināja viņa māte Anita, jo viņa bioloģiskais tēvs aizgāja no ģimenes, kad Fredam bija tikai dažas nedēļas. Freds ar māti dzīvoja ļoti trūcīgi, viņiem nebija ne mājas, ne darba, ne naudas. Viņi dzīvoja baznīcas bēniņos, ēdot bērnu pārtiku, ko nesa draudzes locekļi. Kad Fredam bija divi gadi, Anita iepazinās ar policijas oficieri Bilu, ar kuru drīz vien viņa apprecējās.. Fredam jaunībā patika tā pati mūzika, kas viņa vecākiem, un viņš bieži ākstījās dejojot un iztēlojoties, ka uzstājas publikas priekšā. Kad Freds paaugās, viņš un viņa pusbrālis Korijs (Bila un Anitas dēls) kļuva par Kiss faniem.. Vēlāk Freda ģimene pārvācās no Džeksonvillas, Floridā, uz Gastoniju, Ziemeļkarolīnā, kur Dērsts mācījās Hunter Huss vidusskolā.[1] Šeit viņš sāk aizrauties ar hiphopu un izveido breika dejošanas grupu Reckless Crew. Viņš sāk interesēties par kultūru, kas ir ...
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Vislielāko vīrusu daudzumu inficētie pacienti izdala 2.-3. slimības dienā, t.i., šajā periodā viņi ir "visinfekciozākie", tomēr nelielos, inficēšanai pietiekamos daudzumos vīrusa izdale var saglabāties līdz pat 1-2 nedēļām.. Attiecībā uz sabiedrībā valdošo uzskatu, ka gaisa recirkulācijas sistēmas, piemēram, lidmašīnās, paaugstina saaukstēšanās risku, ASV 2002. gadā veiktais pētījums šādu faktu nav apstiprinājis, tāpēc šobrīd jādomā, ka pārneses ceļam ar nemazgātām rokām ir vislielākā nozīme saaukstēšanās vīrusu izplatībā.. Nereti tiek diskutēts par to, cik bieži gada laikā slimot ar saaukstēšanos ir "normāli". Vidēji pirmsskolas vecuma bērni slimo 6-8 (līdz pat 12) reizes gadā, katru reizi slimībai ilgstot aptuveni 14 dienas, savukārt vecāki bērni un pieaugušie vidēji slimo 2-4 reizes gadā, katru reizi simptomiem ilgstot 5-7 dienas.. Smēķētājiem gan simptomi parasti ilgst vairāk par nedēļu hroniska elpceļu ...
Rubinstein-Taybi syndrome (RSTS) is a rare condition with a prevalence of 1 in 125,000-720,000 births and characterized by clinical features that include facial, dental, and limb dysmorphology and growth retardation. Most cases of RSTS occur sporadically and are caused by de novo mutations. Cytogenetic or molecular abnormalities are detected in only 55% of RSTS cases. Previous genetic studies have yielded inconsistent results due to the variety of methods used for genetic analysis. The purpose of this study was to use whole exome sequencing (WES) to evaluate the genetic causes of RSTS in a young girl presenting with an Autism phenotype. We used the Autism diagnostic observation schedule (ADOS) and Autism diagnostic interview revised (ADI-R) to confirm her diagnosis of Autism. In addition, various questionnaires were used to evaluate other psychiatric features. We used WES to analyze the DNA sequences of the patient and her parents and to search for de novo variants. The patient showed all the typical
One of the major functions of the metal response element-binding transcription factor 1(MTF-1) is to sense and maintain sub-nanomolar to nanomolar zinc levels in response to influxes of labile zinc within the cell. MTF-1 responses to elevated zinc include up regulation of metallothionein (MT-I & II) and efflux transporter (ZnT1) genes. MTF-1 also responds to oxidative stress and heavy metal loads. Due to a lack of liver development, MTF-1 is essential for embryogenesis as determined from knockout mice. The zinc dependence of DNA-binding and interactions with other transcription factors has been identified as major determinants in the homeostatic regulation of labile intracellular zinc by MTF-1. p300 along with its paralog, cyclic-AMP response element binding protein (CBP), have histone acetyltransferase protein scaffold functions and interact with other transcription factors. Previous studies have shown that p300, Sp1 and MTF-1 form a complex. It was also found that a zinc dependent interaction ...