creb binding protein


Summary: A member of the p300-CBP transcription factor family that was initially identified as a binding partner for CAMP RESPONSE ELEMENT-BINDING PROTEIN. Mutations in CREB-binding protein are associated with RUBINSTEIN-TAYBI SYNDROME.

Top Publications

  1. Bhattacherjee V, Horn K, Singh S, Webb C, Pisano M, Greene R. CBP/p300 and associated transcriptional co-activators exhibit distinct expression patterns during murine craniofacial and neural tube development. Int J Dev Biol. 2009;53:1097-104 pubmed publisher
    ..Target genes, and pathways that promote cranial neural tube fusion that are activated by CBP/p300/Carm1/Cited2/Cart1-containing transcriptional complexes await elucidation. ..
  2. Lee C, Martinez Yamout M, Dyson H, Wright P. Structure of the p53 transactivation domain in complex with the nuclear receptor coactivator binding domain of CREB binding protein. Biochemistry. 2010;49:9964-71 pubmed publisher
    ..A salt bridge between D49 of p53 and R2105 of NCBD may contribute to the binding specificity. The structure provides the first insights into simultaneous binding of the AD1 and AD2 motifs to a target protein. ..
  3. Chen G, Zou X, Watanabe H, van Deursen J, Shen J. CREB binding protein is required for both short-term and long-term memory formation. J Neurosci. 2010;30:13066-77 pubmed publisher
    b>CREB binding protein (CBP) is a transcriptional coactivator with histone acetyltransferase activity. Our prior study suggested that CBP might be a key target of presenilins in the regulation of memory formation and neuronal survival...
  4. Yang J, Jiang H, Chen S, Chen J, Li W, Xu S, et al. Lentivirus-mediated RNAi targeting CREB binding protein attenuates neointimal formation and promotes re-endothelialization in balloon injured rat carotid artery. Cell Physiol Biochem. 2010;26:441-8 pubmed publisher
    ..We previously found that CREB binding protein (CBP), a powerful transcriptional coactivator, regulated cell proliferation and apoptosis in vascular ..
  5. Henderson W, Chi E, Ye X, Nguyen C, Tien Y, Zhou B, et al. Inhibition of Wnt/beta-catenin/CREB binding protein (CBP) signaling reverses pulmonary fibrosis. Proc Natl Acad Sci U S A. 2010;107:14309-14 pubmed publisher
    ..Because no effective treatment for IPF exists, selective inhibition of Wnt/beta-catenin-dependent transcription suggests a potential unique therapeutic approach for pulmonary fibrosis. ..
  6. He L, SABET A, Djedjos S, Miller R, Sun X, Hussain M, et al. Metformin and insulin suppress hepatic gluconeogenesis through phosphorylation of CREB binding protein. Cell. 2009;137:635-46 pubmed publisher that both the antidiabetic agent metformin and insulin phosphorylate the transcriptional coactivator CREB binding protein (CBP) at serine 436 via PKC iota/lambda...
  7. Mallik M, Lakhotia S. Improved activities of CREB binding protein, heterogeneous nuclear ribonucleoproteins and proteasome following downregulation of noncoding hsromega transcripts help suppress poly(Q) pathogenesis in fly models. Genetics. 2010;184:927-45 pubmed publisher
    ..reinforce the view that the noncoding hsromega RNA functions as a "hub" in cellular networks to maintain homeostasis by coordinating the functional availability of crucial cellular regulatory proteins. ..
  8. Ryan C, Kindle K, Collins H, Heery D. SUMOylation regulates the nuclear mobility of CREB binding protein and its association with nuclear bodies in live cells. Biochem Biophys Res Commun. 2010;391:1136-41 pubmed publisher
    The lysine acetyltransferase CREB binding protein (CBP) is required for chromatin modification and transcription at many gene promoters. In fixed cells, a large proportion of CBP colocalises to PML or nuclear bodies...
  9. Ferreon J, Lee C, Arai M, Martinez Yamout M, Dyson H, Wright P. Cooperative regulation of p53 by modulation of ternary complex formation with CBP/p300 and HDM2. Proc Natl Acad Sci U S A. 2009;106:6591-6 pubmed publisher
    ..After cellular stress and DNA damage, p53 becomes phosphorylated at T18 and other residues in the AD1 region, releases HDM2 and binds preferentially to CBP/p300, leading to stabilization and activation of p53. ..

More Information


  1. Kim M, McGarry T, O Broin P, Flatow J, Golden A, Licht J. An integrated genome screen identifies the Wnt signaling pathway as a major target of WT1. Proc Natl Acad Sci U S A. 2009;106:11154-9 pubmed publisher
    ..WT1 interference with Wnt signaling represents an important mode of its action relevant to the suppression of tumor growth and guidance of development. ..
  2. Biermann J, Grieshaber P, Goebel U, Martin G, Thanos S, Di Giovanni S, et al. Valproic acid-mediated neuroprotection and regeneration in injured retinal ganglion cells. Invest Ophthalmol Vis Sci. 2010;51:526-34 pubmed publisher
    ..VPA provided neuroprotection and axonal regrowth after ONC. Alterations were observed in several pathways; however, the precise mechanism of VPA-mediated protection is not yet fully understood. ..
  3. Li Y, Huang Y, Amsdell S, Xiao L, O Donnell J, Zhang H. Antidepressant- and anxiolytic-like effects of the phosphodiesterase-4 inhibitor rolipram on behavior depend on cyclic AMP response element binding protein-mediated neurogenesis in the hippocampus. Neuropsychopharmacology. 2009;34:2404-19 pubmed publisher
  4. Senft A, Taylor R, Lei W, Campbell S, Tipper J, Martinez M, et al. Respiratory syncytial virus impairs macrophage IFN-alpha/beta- and IFN-gamma-stimulated transcription by distinct mechanisms. Am J Respir Cell Mol Biol. 2010;42:404-14 pubmed publisher
  5. Liang J, Lei T, Song Y, Yanes N, Qi Y, Fu M. RNA-destabilizing factor tristetraprolin negatively regulates NF-kappaB signaling. J Biol Chem. 2009;284:29383-90 pubmed publisher
    ..Taken together, these data suggest that TTP may also function in vivo as a modulator in suppressing the transcriptional activity of NF-kappaB. ..
  6. Lam B, Zhang W, Ng D, Maruthappu M, Roderick H, Chawla S. CREB-dependent Nur77 induction following depolarization in PC12 cells and neurons is modulated by MEF2 transcription factors. J Neurochem. 2010;112:1065-73 pubmed publisher
    ..We show that while CREB is necessary for Ca2+-activated Nur77 expression MEF2 functions to modulate CREB-dependent Nur77 expression by acting as a repressor in quiescent cells. ..
  7. Manna P, Huhtaniemi I, Stocco D. Mechanisms of protein kinase C signaling in the modulation of 3',5'-cyclic adenosine monophosphate-mediated steroidogenesis in mouse gonadal cells. Endocrinology. 2009;150:3308-17 pubmed publisher
    ..of phosphorylated CREB was tightly correlated with in vivo protein-DNA interactions and recruitment of CREB binding protein to the StAR promoter...
  8. Mazzone G, Rigato I, Ostrow J, Tiribelli C. Bilirubin effect on endothelial adhesion molecules expression is mediated by the NF-kappaB signaling pathway. Biosci Trends. 2009;3:151-7 pubmed
    ..Collectively these data may contribute to explain the protective effect of bilirubin against development of atherosclerosis. ..
  9. Freeman A, Bowers M, Mortimer A, Timmerman C, Roux S, Ramaswami M, et al. A new genetic model of activity-induced Ras signaling dependent pre-synaptic plasticity in Drosophila. Brain Res. 2010;1326:15-29 pubmed publisher
  10. Murray P, Kingsbury T, Krueger B. Failure of Ca2+-activated, CREB-dependent transcription in astrocytes. Glia. 2009;57:828-34 pubmed publisher
    ..The inability of Ca(2+) to signal via CaMKIV may insulate CREB-dependent gene transcription in astrocytes from activation by Ca(2+) waves. ..
  11. O Bryant E, Jordan C. Expression of nuclear receptor coactivators in androgen-responsive and -unresponsive motoneurons. Horm Behav. 2005;47:29-38 pubmed
    ..Our results indicate five different putative cofactors have the potential to participate in motoneuronal responses to androgens, since their distribution overlaps well with the distribution of ARs in these motoneurons. ..
  12. Molenda Figueira H, Williams C, Griffin A, Rutledge E, Blaustein J, Tetel M. Nuclear receptor coactivators function in estrogen receptor- and progestin receptor-dependent aspects of sexual behavior in female rats. Horm Behav. 2006;50:383-92 pubmed
    ..Nuclear receptor coactivators, including Steroid Receptor Coactivator-1 (SRC-1) and CREB Binding Protein (CBP), dramatically enhance ligand-dependent steroid receptor transcriptional activity in vitro...
  13. Zhang M, Poplawski M, Yen K, Cheng H, Bloss E, Zhu X, et al. Role of CBP and SATB-1 in aging, dietary restriction, and insulin-like signaling. PLoS Biol. 2009;7:e1000245 pubmed publisher
    ..Other factors implicated in lifespan extension are also CBP-binding partners, suggesting that CBP constitutes a common factor in the modulation of lifespan and disease burden by DR and the insulin/IGF1 signaling pathway. ..
  14. Chen J, Jiang H, Zhu L, Wang L, Xu L. Downregulation of CREB-binding protein expression sensitizes endothelial cells to serum-deprived apoptosis: important role of nitric oxide. Mol Cell Biochem. 2010;337:159-66 pubmed publisher
    ..These results indicated that CBP silencing is associated with decreased eNOS expression and NO production, and therefore concomitantly increased the sensitivity of ECs toward apoptosis. ..
  15. Marcos B, Cabero M, Solas M, Aisa B, Ramirez M. Signalling pathways associated with 5-HT6 receptors: relevance for cognitive effects. Int J Neuropsychopharmacol. 2010;13:775-84 pubmed publisher
  16. Kjaergaard M, Teilum K, Poulsen F. Conformational selection in the molten globule state of the nuclear coactivator binding domain of CBP. Proc Natl Acad Sci U S A. 2010;107:12535-40 pubmed publisher
    ..The nuclear coactivator binding domain (NCBD) of CREB binding protein is particularly interesting in this respect as structural studies of its complexes have shown that NCBD ..
  17. Wang Z, Ma W, Chabot J, Quirion R. Calcitonin gene-related peptide as a regulator of neuronal CaMKII-CREB, microglial p38-NF?B and astroglial ERK-Stat1/3 cascades mediating the development of tolerance to morphine-induced analgesia. Pain. 2010;151:194-205 pubmed publisher
    ..Targeting CGRP-associated signaling molecules may prolong or restore morphine's analgesic properties upon a chronic exposure. ..
  18. Wang X, Arai S, Song X, Reichart D, Du K, Pascual G, et al. Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription. Nature. 2008;454:126-30 pubmed publisher
  19. Song B, Kim J, Kim C, Han Y, Lee D, Lee K, et al. Prostacyclin stimulates embryonic development via regulation of the cAMP response element-binding protein-cyclo-oxygenase-2 signalling pathway in cattle. Reprod Fertil Dev. 2009;21:400-7 pubmed
    ..These results suggest that PGI(2) improves the developmental competence of embryos via regulation of the cAMP response element-binding protein-COX-2 signalling pathway in cattle. ..
  20. Liu X, Liu W, Jin Y, Yu W, Liu L, Yu H. Effects of subchronic perfluorooctane sulfonate exposure of rats on calcium-dependent signaling molecules in the brain tissue. Arch Toxicol. 2010;84:471-9 pubmed publisher
    ..These results indicated that, at least in part, the neurotoxic effect induced by PFOS is mediated by the Ca(2+)-dependent molecules in calcium signaling. ..
  21. Chen Y, Dominguez Brauer C, Wang Z, Asara J, Costa R, Tyner A, et al. A conserved phosphorylation site within the forkhead domain of FoxM1B is required for its activation by cyclin-CDK1. J Biol Chem. 2009;284:30695-707 pubmed publisher
  22. Sepulveda F, Opazo C, Aguayo L. Alzheimer beta-amyloid blocks epileptiform activity in hippocampal neurons. Mol Cell Neurosci. 2009;41:420-8 pubmed publisher
    ..In conclusion, neurons exposed to aggregated Abeta(1-40) showed a reduced level of neuronal plasticity and this suggests that they might be acting as anti-epileptiform modulators. ..
  23. Han E, Kim H, Hwang Y, Choi J, Im J, Park B, et al. The role of cyclooxygenase-2-dependent signaling via cyclic AMP response element activation on aromatase up-regulation by o,p'-DDT in human breast cancer cells. Toxicol Lett. 2010;198:331-41 pubmed publisher
  24. Andrews P, He Z, Popadiuk C, Kao K. The transcriptional activity of Pygopus is enhanced by its interaction with cAMP-response-element-binding protein (CREB)-binding protein. Biochem J. 2009;422:493-501 pubmed publisher
  25. Chiang P, Lee N, Chien N, Hwu W, Spector E, Tsai A. Somatic and germ-line mosaicism in Rubinstein-Taybi syndrome. Am J Med Genet A. 2009;149A:1463-7 pubmed publisher
    ..Additional family studies are required to determine how common somatic and/or gonadal mosaicism is present in RSTS patients...
  26. Kasper L, Lerach S, Wang J, Wu S, Jeevan T, Brindle P. CBP/p300 double null cells reveal effect of coactivator level and diversity on CREB transactivation. EMBO J. 2010;29:3660-72 pubmed publisher
    ..This model suggests how gene expression patterns could be tuned by altering coactivator availability rather than by changing signal input or transcription factor levels. ..
  27. Eckel Mahan K, Phan T, Han S, Wang H, Chan G, Scheiner Z, et al. Circadian oscillation of hippocampal MAPK activity and cAmp: implications for memory persistence. Nat Neurosci. 2008;11:1074-82 pubmed
    ..These data suggest that the persistence of long-term memories may depend on reactivation of the cAMP/MAPK/CREB transcriptional pathway in the hippocampus during the circadian cycle. ..
  28. Ploski J, Park K, Ping J, Monsey M, Schafe G. Identification of plasticity-associated genes regulated by Pavlovian fear conditioning in the lateral amygdala. J Neurochem. 2010;112:636-50 pubmed publisher
  29. Galéra C, Taupiac E, Fraisse S, Naudion S, Toussaint E, Rooryck Thambo C, et al. Socio-behavioral characteristics of children with Rubinstein-Taybi syndrome. J Autism Dev Disord. 2009;39:1252-60 pubmed publisher
    ..The presence of an identified CREBBP gene abnormality was possibly related to the motor difficulties through impaired motor skills learning. ..
  30. Alvarez Y, Municio C, Alonso S, Sánchez Crespo M, Fernández N. The induction of IL-10 by zymosan in dendritic cells depends on CREB activation by the coactivators CREB-binding protein and TORC2 and autocrine PGE2. J Immunol. 2009;183:1471-9 pubmed publisher
  31. Cloutier N, Flamand L. Kaposi sarcoma-associated herpesvirus latency-associated nuclear antigen inhibits interferon (IFN) beta expression by competing with IFN regulatory factor-3 for binding to IFNB promoter. J Biol Chem. 2010;285:7208-21 pubmed publisher
    ..The ability of LANA-1 to inhibit IFNB gene expression highlights a new role for this protein in cellular gene modulation and immune evasion strategies...
  32. Lee G, Craik C. Trapping moving targets with small molecules. Science. 2009;324:213-5 pubmed publisher
    ..Although multiple methodologies exist to probe protein dynamics and ligand binding, our current discussion highlights the use of nuclear magnetic resonance spectroscopy in the drug discovery and design process. ..
  33. Gabryel B, Bernacki J. Effect of FK506 and cyclosporine A on the expression of BDNF, tyrosine kinase B and p75 neurotrophin receptors in astrocytes exposed to simulated ischemia in vitro. Cell Biol Int. 2009;33:739-48 pubmed publisher
    ..The results RT-PCR and Western blot analysis provided further evidence of a modulating influence of the drugs on the expression of trkB and p75(NTR) genes and their protein products in ischemic astrocytes. ..
  34. Tie F, Banerjee R, Stratton C, Prasad Sinha J, Stepanik V, Zlobin A, et al. CBP-mediated acetylation of histone H3 lysine 27 antagonizes Drosophila Polycomb silencing. Development. 2009;136:3131-41 pubmed publisher
    ..We propose that TRX-dependent acetylation of H3K27 by CBP prevents H3K27me3 at Polycomb target genes and constitutes a key part of the molecular mechanism by which TRX antagonizes or prevents Polycomb silencing. ..
  35. Gomez R, Pentz E, Jin X, Cordaillat M, Sequeira Lopez M. CBP and p300 are essential for renin cell identity and morphological integrity of the kidney. Am J Physiol Heart Circ Physiol. 2009;296:H1255-62 pubmed publisher
    ..Results show that the histone acetyltransferases CBP and p300 are necessary for maintenance of renin cell identity and structural integrity of the kidney. ..
  36. Jancic D, Lopez de Armentia M, Valor L, Olivares R, Barco A. Inhibition of cAMP response element-binding protein reduces neuronal excitability and plasticity, and triggers neurodegeneration. Cereb Cortex. 2009;19:2535-47 pubmed publisher
  37. Nelson M, Kang H, Lee G, Blaszczak A, Lau D, McIntosh L, et al. Ras signaling requires dynamic properties of Ets1 for phosphorylation-enhanced binding to coactivator CBP. Proc Natl Acad Sci U S A. 2010;107:10026-31 pubmed publisher
    ..This detailed structural and mechanistic information will guide strategies for targeting ETS proteins in human disease. ..
  38. De Rasmo D, Signorile A, Papa F, Roca E, Papa S. cAMP/Ca2+ response element-binding protein plays a central role in the biogenesis of respiratory chain proteins in mammalian cells. IUBMB Life. 2010;62:447-52 pubmed publisher
    ..Activation of this network of transcriptional complexes results in concerted promotion of the expression of nuclear and mitochondrial genes encoding subunits of oxidative phosphorylation complexes. ..
  39. Tamburella A, Micale V, Navarria A, Drago F. Antidepressant properties of the 5-HT4 receptor partial agonist, SL65.0155: behavioral and neurochemical studies in rats. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33:1205-10 pubmed publisher
    ..No change was found in Bax expression in any treated group. These findings give further support to the hypothesis that the stimulation of serotonin 5-HT(4) receptors may be a therapeutic target for depression. ..
  40. Burke S, Collier J, Scott D. cAMP opposes the glucose-mediated induction of the L-PK gene by preventing the recruitment of a complex containing ChREBP, HNF4alpha, and CBP. FASEB J. 2009;23:2855-65 pubmed publisher
    ..response element binding protein (ChREBP), hepatic nuclear factor 4alpha (HNF4alpha), and the coactivator CREB binding protein (CBP) are required for the glucose response of the L-PK gene and are recruited to the promoter by glucose...
  41. Ishizu A, Abe A, Miyatake Y, Baba T, Iinuma C, Tomaru U, et al. Cyclic AMP response element-binding protein is implicated in IL-6 production from arthritic synovial cells. Mod Rheumatol. 2010;20:134-8 pubmed publisher
    ..These findings suggest that CREB is implicated in IL-6 production from synovial cells and plays an important role in RA pathogenesis. ..
  42. Kumar S, Sun X, Sharma S, Aggarwal S, Ravi K, Fineman J, et al. GTP cyclohydrolase I expression is regulated by nitric oxide: role of cyclic AMP. Am J Physiol Lung Cell Mol Physiol. 2009;297:L309-17 pubmed publisher
    ..These data suggest that NO increases BH(4) levels through a cAMP/CREB-mediated increase in GCH1 transcription and that the eNOS uncoupling associated with exogenous NO does not involved reduced BH(4) levels. ..
  43. Biermann J, Lagrèze W, Dimitriu C, Stoykow C, Goebel U. Preconditioning with inhalative carbon monoxide protects rat retinal ganglion cells from ischemia/reperfusion injury. Invest Ophthalmol Vis Sci. 2010;51:3784-91 pubmed publisher
    ..Further studies are needed to evaluate whether CO posttreatment may represent a therapeutic option counteracting ischemic neuronal injury. ..
  44. Wang J, Weaver I, Gauthier Fisher A, Wang H, He L, Yeomans J, et al. CBP histone acetyltransferase activity regulates embryonic neural differentiation in the normal and Rubinstein-Taybi syndrome brain. Dev Cell. 2010;18:114-25 pubmed publisher
    ..Here, we ask about neural precursors, focusing on CREB binding protein (CBP), a histone acetyltransferase that, when haploinsufficient, causes Rubinstein-Taybi syndrome (RTS), a ..
  45. Spooren A, Kooijman R, Lintermans B, Van Craenenbroeck K, Vermeulen L, Haegeman G, et al. Cooperation of NFkappaB and CREB to induce synergistic IL-6 expression in astrocytes. Cell Signal. 2010;22:871-81 pubmed publisher
    ..Interestingly, whereas CREB and NFkappaB usually compete for the limiting cofactor CREB binding protein (CBP), we detected enhanced recruitment of CBP at the IL-6 promoter in our system...
  46. Mombereau C, Gur T, Onksen J, Blendy J. Differential effects of acute and repeated citalopram in mouse models of anxiety and depression. Int J Neuropsychopharmacol. 2010;13:321-34 pubmed publisher
    ..These data demonstrate that behavioural responses to citalopram are dependent on the frequency of its administration, and that these responses are differentially dependent on CREB function. ..
  47. Costes S, Vandewalle B, Tourrel Cuzin C, Broca C, Linck N, Bertrand G, et al. Degradation of cAMP-responsive element-binding protein by the ubiquitin-proteasome pathway contributes to glucotoxicity in beta-cells and human pancreatic islets. Diabetes. 2009;58:1105-15 pubmed publisher
    ..These studies demonstrate that the CREB degradation by the ubiquitin-proteasome pathway contributes to beta-cell dysfunction and death upon glucotoxicity and provide new insight into the cellular mechanisms of glucotoxicity. ..
  48. Bimpaki E, Nesterova M, Stratakis C. Abnormalities of cAMP signaling are present in adrenocortical lesions associated with ACTH-independent Cushing syndrome despite the absence of mutations in known genes. Eur J Endocrinol. 2009;161:153-61 pubmed publisher
    ..It is probable that epigenetic events or additional defects of genes involved in this pathway are responsible for this phenomenon. ..
  49. Clarke D, Clifford R, Jindarat S, Proud D, Pang L, Belvisi M, et al. TNF? and IFN? synergistically enhance transcriptional activation of CXCL10 in human airway smooth muscle cells via STAT-1, NF-?B, and the transcriptional coactivator CREB-binding protein. J Biol Chem. 2010;285:29101-10 pubmed publisher
  50. Qi X, Lin W, Wang D, Pan Y, Wang W, Sun M. A role for the extracellular signal-regulated kinase signal pathway in depressive-like behavior. Behav Brain Res. 2009;199:203-9 pubmed publisher
    ..These findings demonstrate that the ERK pathway in either the dHP or mPFC participates in the pathophysiology of the depressive-like behavior, and may have pivotal role in human depression. ..
  51. Jiang Z, Belforte J, Lu Y, Yabe Y, Pickel J, Smith C, et al. eIF2alpha Phosphorylation-dependent translation in CA1 pyramidal cells impairs hippocampal memory consolidation without affecting general translation. J Neurosci. 2010;30:2582-94 pubmed publisher
    ..The present study sheds light on the critical importance of gene-specific translations for hippocampal memory consolidation. ..
  52. Lam B, Zhang W, Enticknap N, Haggis E, Cader M, Chawla S. Inverse regulation of plasticity-related immediate early genes by calcineurin in hippocampal neurons. J Biol Chem. 2009;284:12562-71 pubmed publisher
    ..Conversely, SRE-mediated c-fos induction in the absence of a functional CRE was enhanced by calcineurin inhibitors. Our experiments thus implicate calcineurin as a negative regulator of SRE-dependent neuronal genes. ..
  53. Eichenbaum K, Rodríguez Y, Mezei M, Osman R. The energetics of the acetylation switch in p53-mediated transcriptional activation. Proteins. 2010;78:447-56 pubmed publisher
    ..8 kcal/mol. An analysis of residue contributions to the binding energy using an MM-GBSA approach agrees with the FEP results and sheds additional light on the origin of selectivity in p53 binding to the CBP bromodomain. ..