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Gene Review

Creb1  -  cAMP responsive element binding protein 1

Rattus norvegicus

Synonyms: CREB-1, Creb-1, Cyclic AMP-responsive element-binding protein 1, cAMP-responsive element-binding protein 1
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Disease relevance of Creb1


Psychiatry related information on Creb1


High impact information on Creb1

  • Defining the CREB regulon: a genome-wide analysis of transcription factor regulatory regions [10].
  • Because CBP represents a common factor, required in addition to distinct coactivators for function of nuclear receptors, CREB, and AP-1, we suggest that CBP/p300 serves as an integrator of multiple signal transduction pathways within the nucleus [11].
  • We propose that phosphorylation by kinase A may stimulate CREB activity in part by modulating the structure of alpha and thus may stimulate its ability to interact with other proteins in the polymerase II complex [12].
  • Circular dichroism data on a synthetic "alpha peptide" combined with results from in vitro mutagenesis experiments support the hypothesis that the alpha region contains an amphipathic alpha helix whose structure is critical to CREB activity [12].
  • Both proteins are expressed in eukaryotic cells, although the activity of CREB is 10-fold higher than that of delta CREB [12].

Chemical compound and disease context of Creb1


Biological context of Creb1


Anatomical context of Creb1


Associations of Creb1 with chemical compounds

  • Our findings suggest a hypothesis where stimulation of N-methyl-d-aspartate receptors signals CREB activation to enhance PS-1 gene product expression that contributes to normal neuronal functions [24].
  • We examined signaling pathways that are responsible for AngII-induced phosphorylation of CRE-binding protein (CREB) at serine 133 that is a critical marker for the activation in rat vascular smooth muscle cells (VSMC) [1].
  • These findings support that not only CREB but also USF1/USF2 contributes to Ca(2+) signal-mediated activation of BDNF-PI through the recognition of an overlapping CRE and USF-binding element [25].
  • Our results uncover a novel mechanism by which the PKA/ERK1/2 signaling network engaged by glucagon, in situation of low glucose concentration, regulates phosphorylation of CREB, a transcription factor crucial for normal beta cell function and survival [26].
  • Rapid effects of retinoic acid on CREB and ERK phosphorylation in neuronal cells [18].

Physical interactions of Creb1


Enzymatic interactions of Creb1

  • FPI alone resulted in significantly elevated levels of hippocampal phosphorylated synapsin I and phosphorylated cyclic AMP response element-binding-protein (CREB) at postinjury day 7, of which phosphorylated CREB remained elevated at postinjury day 21 [32].
  • These factors may act as the eventual repressors for BDNF expression via competition and heterodimerization with phosphorylated CREB, a transcription factor important for BDNF expression [33].
  • In experiments with dominant-negative peptides and dihydropyridine-resistant CaV1.3a mutants, we demonstrated an importance of Shank-binding motif in CaV1.3a sequence for phosphorylated cAMP response element-binding protein (pCREB) signaling in cultured hippocampal neurons [34].

Regulatory relationships of Creb1


Other interactions of Creb1


Analytical, diagnostic and therapeutic context of Creb1


  1. Critical role of cAMP-response element-binding protein for angiotensin II-induced hypertrophy of vascular smooth muscle cells. Funakoshi, Y., Ichiki, T., Takeda, K., Tokuno, T., Iino, N., Takeshita, A. J. Biol. Chem. (2002) [Pubmed]
  2. A neuroprotective role of extracellular signal-regulated kinase in N-acetyl-O-methyldopamine-treated hippocampal neurons after exposure to in vitro and in vivo ischemia. Park, E.M., Joh, T.H., Volpe, B.T., Chu, C.K., Song, G., Cho, S. Neuroscience (2004) [Pubmed]
  3. Chronic morphine exposure increases the phosphorylation of MAP kinases and the transcription factor CREB in dorsal root ganglion neurons: an in vitro and in vivo study. Ma, W., Zheng, W.H., Powell, K., Jhamandas, K., Quirion, R. Eur. J. Neurosci. (2001) [Pubmed]
  4. Phenylephrine induces activation of CREB in adult rat cardiac myocytes through MSK1 and PKA signaling pathways. Markou, T., Hadzopoulou-Cladaras, M., Lazou, A. J. Mol. Cell. Cardiol. (2004) [Pubmed]
  5. Striatal modulation of cAMP-response-element-binding protein (CREB) after excitotoxic lesions: implications with neuronal vulnerability in Huntington's disease. Giampà, C., DeMarch, Z., D'Angelo, V., Morello, M., Martorana, A., Sancesario, G., Bernardi, G., Fusco, F.R. Eur. J. Neurosci. (2006) [Pubmed]
  6. Beta -amyloid-(1-42) impairs activity-dependent cAMP-response element-binding protein signaling in neurons at concentrations in which cell survival Is not compromised. Tong, L., Thornton, P.L., Balazs, R., Cotman, C.W. J. Biol. Chem. (2001) [Pubmed]
  7. Endogenous BDNF is required for long-term memory formation in the rat parietal cortex. Alonso, M., Bekinschtein, P., Cammarota, M., Vianna, M.R., Izquierdo, I., Medina, J.H. Learn. Mem. (2005) [Pubmed]
  8. CREB phosphorylation and c-Fos expression in the hippocampus of rats during acquisition and recall of a socially transmitted food preference. Countryman, R.A., Orlowski, J.D., Brightwell, J.J., Oskowitz, A.Z., Colombo, P.J. Hippocampus. (2005) [Pubmed]
  9. Dopamine-dependent increases in phosphorylation of cAMP response element binding protein (CREB) during precipitated morphine withdrawal in primary cultures of rat striatum. Chartoff, E.H., Papadopoulou, M., Konradi, C., Carlezon, W.A. J. Neurochem. (2003) [Pubmed]
  10. Defining the CREB regulon: a genome-wide analysis of transcription factor regulatory regions. Impey, S., McCorkle, S.R., Cha-Molstad, H., Dwyer, J.M., Yochum, G.S., Boss, J.M., McWeeney, S., Dunn, J.J., Mandel, G., Goodman, R.H. Cell (2004) [Pubmed]
  11. A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors. Kamei, Y., Xu, L., Heinzel, T., Torchia, J., Kurokawa, R., Gloss, B., Lin, S.C., Heyman, R.A., Rose, D.W., Glass, C.K., Rosenfeld, M.G. Cell (1996) [Pubmed]
  12. Characterization of a bipartite activator domain in transcription factor CREB. Yamamoto, K.K., Gonzalez, G.A., Menzel, P., Rivier, J., Montminy, M.R. Cell (1990) [Pubmed]
  13. Cooperative effects between protein kinase A and p44/p42 mitogen-activated protein kinase to promote cAMP-responsive element binding protein activation after beta cell stimulation by glucose and its alteration due to glucotoxicity. Costes, S., Longuet, C., Broca, C., Faruque, O., Hani, e.l. .H., Bataille, D., Dalle, S. Ann. N. Y. Acad. Sci. (2004) [Pubmed]
  14. cAMP-response element-binding protein mediates prostaglandin F2alpha-induced hypertrophy of vascular smooth muscle cells. Fukuyama, K., Ichiki, T., Ono, H., Tokunou, T., Iino, N., Masuda, S., Ohtsubo, H., Takeshita, A. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  15. Regulation of c-fos gene expression by lipopolysaccharide and cycloheximide in C6 rat glioma cells. Kim, Y.H., Choi, M.R., Song, D.K., Huh, S.O., Jang, C.G., Suh, H.W. Brain Res. (2000) [Pubmed]
  16. Platelet-derived growth factor BB induces nuclear export and proteasomal degradation of CREB via phosphatidylinositol 3-kinase/Akt signaling in pulmonary artery smooth muscle cells. Garat, C.V., Fankell, D., Erickson, P.F., Reusch, J.E., Bauer, N.N., McMurtry, I.F., Klemm, D.J. Mol. Cell. Biol. (2006) [Pubmed]
  17. CREB modulates the functional output of nucleus accumbens neurons: a critical role of N-methyl-D-aspartate glutamate receptor (NMDAR) receptors. Huang, Y.H., Lin, Y., Brown, T.E., Han, M.H., Saal, D.B., Neve, R.L., Zukin, R.S., Sorg, B.A., Nestler, E.J., Malenka, R.C., Dong, Y. J. Biol. Chem. (2008) [Pubmed]
  18. Rapid effects of retinoic acid on CREB and ERK phosphorylation in neuronal cells. Cañón, E., Cosgaya, J.M., Scsucova, S., Aranda, A. Mol. Biol. Cell (2004) [Pubmed]
  19. Insulin-like growth factor I-mediated activation of the transcription factor cAMP response element-binding protein in PC12 cells. Involvement of p38 mitogen-activated protein kinase-mediated pathway. Pugazhenthi, S., Boras, T., O'Connor, D., Meintzer, M.K., Heidenreich, K.A., Reusch, J.E. J. Biol. Chem. (1999) [Pubmed]
  20. p38 MAPK-mediated transcriptional activation of inducible nitric-oxide synthase in glial cells. Roles of nuclear factors, nuclear factor kappa B, cAMP response element-binding protein, CCAAT/enhancer-binding protein-beta, and activating transcription factor-2. Bhat, N.R., Feinstein, D.L., Shen, Q., Bhat, A.N. J. Biol. Chem. (2002) [Pubmed]
  21. BDNF-induced LTP in dentate gyrus is impaired with age: analysis of changes in cell signaling events. Gooney, M., Messaoudi, E., Maher, F.O., Bramham, C.R., Lynch, M.A. Neurobiol. Aging (2004) [Pubmed]
  22. Endothelin increases expression of exon III- and exon IV-containing brain-derived neurotrophic factor transcripts in cultured astrocytes and rat brain. Koyama, Y., Tsujikawa, K., Matsuda, T., Baba, A. J. Neurosci. Res. (2005) [Pubmed]
  23. Selective chronic stress-induced in vivo ERK1/2 hyperphosphorylation in medial prefrontocortical dendrites: implications for stress-related cortical pathology? Trentani, A., Kuipers, S.D., Ter Horst, G.J., Den Boer, J.A. Eur. J. Neurosci. (2002) [Pubmed]
  24. Activated cAMP-response element-binding protein regulates neuronal expression of presenilin-1. Mitsuda, N., Ohkubo, N., Tamatani, M., Lee, Y.D., Taniguchi, M., Namikawa, K., Kiyama, H., Yamaguchi, A., Sato, N., Sakata, K., Ogihara, T., Vitek, M.P., Tohyama, M. J. Biol. Chem. (2001) [Pubmed]
  25. Involvement of an upstream stimulatory factor as well as cAMP-responsive element-binding protein in the activation of brain-derived neurotrophic factor gene promoter I. Tabuchi, A., Sakaya, H., Kisukeda, T., Fushiki, H., Tsuda, M. J. Biol. Chem. (2002) [Pubmed]
  26. Glucagon promotes cAMP-response element-binding protein phosphorylation via activation of ERK1/2 in MIN6 cell line and isolated islets of Langerhans. Dalle, S., Longuet, C., Costes, S., Broca, C., Faruque, O., Fontés, G., Hani, e.l. .H., Bataille, D. J. Biol. Chem. (2004) [Pubmed]
  27. Food restriction increases NMDA receptor-mediated calcium-calmodulin kinase II and NMDA receptor/extracellular signal-regulated kinase 1/2-mediated cyclic amp response element-binding protein phosphorylation in nucleus accumbens upon D-1 dopamine receptor stimulation in rats. Haberny, S.L., Carr, K.D. Neuroscience (2005) [Pubmed]
  28. A calcium/calmodulin kinase pathway connects brain-derived neurotrophic factor to the cyclic AMP-responsive transcription factor in the rat hippocampus. Blanquet, P.R., Mariani, J., Derer, P. Neuroscience (2003) [Pubmed]
  29. Activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase signaling pathway leading to cyclic AMP response element-binding protein phosphorylation is required for the long-term facilitation process of aversive olfactory learning in young rats. Zhang, J.J., Okutani, F., Inoue, S., Kaba, H. Neuroscience (2003) [Pubmed]
  30. Identification of a functional AP1 element in the rat vasopressin gene promoter. Yoshida, M., Iwasaki, Y., Asai, M., Takayasu, S., Taguchi, T., Itoi, K., Hashimoto, K., Oiso, Y. Endocrinology (2006) [Pubmed]
  31. The mitogen-activated protein kinase cascade couples PKA and PKC to cAMP response element binding protein phosphorylation in area CA1 of hippocampus. Roberson, E.D., English, J.D., Adams, J.P., Selcher, J.C., Kondratick, C., Sweatt, J.D. J. Neurosci. (1999) [Pubmed]
  32. Voluntary exercise following traumatic brain injury: brain-derived neurotrophic factor upregulation and recovery of function. Griesbach, G.S., Hovda, D.A., Molteni, R., Wu, A., Gomez-Pinilla, F. Neuroscience (2004) [Pubmed]
  33. Expression profiling to understand actions of NMDA/glutamate receptor antagonists in rat brain. Törönen, P., Storvik, M., Lindén, A.M., Kontkane, O., Marvanová, M., Lakso, M., Castrén, E., Wong, G. Neurochem. Res. (2002) [Pubmed]
  34. Association of CaV1.3 L-type calcium channels with Shank. Zhang, H., Maximov, A., Fu, Y., Xu, F., Tang, T.S., Tkatch, T., Surmeier, D.J., Bezprozvanny, I. J. Neurosci. (2005) [Pubmed]
  35. Apolipoprotein E4 stimulates cAMP response element-binding protein transcriptional activity through the extracellular signal-regulated kinase pathway. Ohkubo, N., Mitsuda, N., Tamatani, M., Yamaguchi, A., Lee, Y.D., Ogihara, T., Vitek, M.P., Tohyama, M. J. Biol. Chem. (2001) [Pubmed]
  36. Potentiation of a survival signal in the ischemic heart by resveratrol through p38 mitogen-activated protein kinase/mitogen- and stress-activated protein kinase 1/cAMP response element-binding protein signaling. Das, S., Tosaki, A., Bagchi, D., Maulik, N., Das, D.K. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  37. Endothelin-1- and depolarization-induced differential regulation of cAMP response element-binding protein in proliferating and developed vascular smooth muscle. Egan, C.G., Nixon, G.F. Cell. Signal. (2004) [Pubmed]
  38. Requirement of Ras for the activation of mitogen-activated protein kinase by calcium influx, cAMP, and neurotrophin in hippocampal neurons. Iida, N., Namikawa, K., Kiyama, H., Ueno, H., Nakamura, S., Hattori, S. J. Neurosci. (2001) [Pubmed]
  39. Insulin-like growth factor-1 (IGF-1) induces the activation/phosphorylation of Akt kinase and cAMP response element-binding protein (CREB) by activating different signaling pathways in PC12 cells. Zheng, W.H., Quirion, R. BMC neuroscience [electronic resource]. (2006) [Pubmed]
  40. Corticotropin-releasing factor type 1 and type 2alpha receptors regulate phosphorylation of calcium/cyclic adenosine 3',5'-monophosphate response element-binding protein and activation of p42/p44 mitogen-activated protein kinase. Rossant, C.J., Pinnock, R.D., Hughes, J., Hall, M.D., McNulty, S. Endocrinology (1999) [Pubmed]
  41. Extracellular receptor kinase and cAMP response element binding protein activation in the neonatal rat heart after perinatal cocaine exposure. Sun, L.S., Quamina, A. Pediatr. Res. (2004) [Pubmed]
  42. Cell-type-specific binding of the transcription factor CREB to the cAMP-response element. Cha-Molstad, H., Keller, D.M., Yochum, G.S., Impey, S., Goodman, R.H. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
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