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Gene Review

Creb1  -  cAMP responsive element binding protein 1

Mus musculus

Synonyms: 2310001E10Rik, 3526402H21Rik, AV083133, CREB-1, Creb, ...
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Disease relevance of Creb1


Psychiatry related information on Creb1

  • Considering whether FosB and adrenergic signaling might share a signaling pathway important for maternal behavior, we examined the role of a potential intermediary, cyclic AMP response element-binding protein (CREB) [6].
  • Thus, CREB-dependent gene transcription is a factor in the onset of behavioral manifestations of opiate dependence [7].
  • In vivo, light-induced phase shifts in locomotor activity were consistently accompanied by CREB phosphorylation in the SCN of both strains [8].
  • CREBcomp but not CREBalphadelta F1 hybrids were impaired in water maze learning and fear conditioning, demonstrating a CREB gene dosage effect [9].
  • These results suggest that the CREB protein contributes to the mechanisms by which wakefulness is maintained and demonstrate that specific genetic alterations in species as diverse as Drosophila and mice produce similar phenotypes in arousal and wakefulness [10].

High impact information on Creb1

  • The beneficial effect of the Uch-L1 fusion protein is associated with restoration of normal levels of the PKA-regulatory subunit IIalpha, PKA activity, and CREB phosphorylation [11].
  • Expression of constitutively active CREB protein facilitates the late phase of long-term potentiation by enhancing synaptic capture [12].
  • Nerve growth factor activates a Ras-dependent protein kinase that stimulates c-fos transcription via phosphorylation of CREB [13].
  • Here we show that mice carrying a targeted disruption of the cyclic AMP (cAMP) response element binding (CREB) protein gene, or overexpressing a dominant-negative CREB inhibitor, exhibit fasting hypoglycaemia [corrected] and reduced expression of gluconeogenic enzymes [14].
  • Overexpression of PGC-1 in CREB-deficient mice restored glucose homeostasis and rescued expression of gluconeogenic genes [14].

Chemical compound and disease context of Creb1


Biological context of Creb1


Anatomical context of Creb1


Associations of Creb1 with chemical compounds


Physical interactions of Creb1


Enzymatic interactions of Creb1


Co-localisations of Creb1


Regulatory relationships of Creb1


Other interactions of Creb1


Analytical, diagnostic and therapeutic context of Creb1


  1. Identification of a membrane Ig-induced p38 mitogen-activated protein kinase module that regulates cAMP response element binding protein phosphorylation and transcriptional activation in CH31 B cell lymphomas. Swart, J.M., Bergeron, D.M., Chiles, T.C. J. Immunol. (2000) [Pubmed]
  2. Histone acetylation and activation of cAMP-response element-binding protein regulate transcriptional activation of MKP-M in lipopolysaccharide-stimulated macrophages. Musikacharoen, T., Yoshikai, Y., Matsuguchi, T. J. Biol. Chem. (2003) [Pubmed]
  3. Essential role of CREB family proteins during Xenopus embryogenesis. Lutz, B., Schmid, W., Niehrs, C., Schütz, G. Mech. Dev. (1999) [Pubmed]
  4. CREB-induced transcriptional activation depends on mGluR6 in rod bipolar cells. Yoshida, K., Imaki, J., Okamoto, Y., Iwakabe, H., Fujisawa, H., Matsuda, A., Nakanisi, S., Matsuda, H., Hagiwara, M. Brain Res. Mol. Brain Res. (1998) [Pubmed]
  5. Activation of AP-1 and CRE-dependent gene expression via mu-opioid receptor. Bilecki, W., Wawrzczak-Bargiela, A., Przewlocki, R. J. Neurochem. (2004) [Pubmed]
  6. Cyclic AMP response element-binding protein is required for normal maternal nurturing behavior. Jin, S.H., Blendy, J.A., Thomas, S.A. Neuroscience (2005) [Pubmed]
  7. Reduction of morphine abstinence in mice with a mutation in the gene encoding CREB. Maldonado, R., Blendy, J.A., Tzavara, E., Gass, P., Roques, B.P., Hanoune, J., Schütz, G. Science (1996) [Pubmed]
  8. CREB in the mouse SCN: a molecular interface coding the phase-adjusting stimuli light, glutamate, PACAP, and melatonin for clockwork access. von Gall, C., Duffield, G.E., Hastings, M.H., Kopp, M.D., Dehghani, F., Korf, H.W., Stehle, J.H. J. Neurosci. (1998) [Pubmed]
  9. Deficits in memory tasks of mice with CREB mutations depend on gene dosage. Gass, P., Wolfer, D.P., Balschun, D., Rudolph, D., Frey, U., Lipp, H.P., Schütz, G. Learn. Mem. (1998) [Pubmed]
  10. Genetic evidence for a role of CREB in sustained cortical arousal. Graves, L.A., Hellman, K., Veasey, S., Blendy, J.A., Pack, A.I., Abel, T. J. Neurophysiol. (2003) [Pubmed]
  11. Ubiquitin hydrolase Uch-L1 rescues beta-amyloid-induced decreases in synaptic function and contextual memory. Gong, B., Cao, Z., Zheng, P., Vitolo, O.V., Liu, S., Staniszewski, A., Moolman, D., Zhang, H., Shelanski, M., Arancio, O. Cell (2006) [Pubmed]
  12. Expression of constitutively active CREB protein facilitates the late phase of long-term potentiation by enhancing synaptic capture. Barco, A., Alarcon, J.M., Kandel, E.R. Cell (2002) [Pubmed]
  13. Nerve growth factor activates a Ras-dependent protein kinase that stimulates c-fos transcription via phosphorylation of CREB. Ginty, D.D., Bonni, A., Greenberg, M.E. Cell (1994) [Pubmed]
  14. CREB regulates hepatic gluconeogenesis through the coactivator PGC-1. Herzig, S., Long, F., Jhala, U.S., Hedrick, S., Quinn, R., Bauer, A., Rudolph, D., Schutz, G., Yoon, C., Puigserver, P., Spiegelman, B., Montminy, M. Nature (2001) [Pubmed]
  15. Mechanisms of lung neutrophil activation after hemorrhage or endotoxemia: roles of reactive oxygen intermediates, NF-kappa B, and cyclic AMP response element binding protein. Shenkar, R., Abraham, E. J. Immunol. (1999) [Pubmed]
  16. The oxidized lipid and lipoxygenase product 12(S)-hydroxyeicosatetraenoic acid induces hypertrophy and fibronectin transcription in vascular smooth muscle cells via p38 MAPK and cAMP response element-binding protein activation. Mediation of angiotensin II effects. Reddy, M.A., Thimmalapura, P.R., Lanting, L., Nadler, J.L., Fatima, S., Natarajan, R. J. Biol. Chem. (2002) [Pubmed]
  17. Cocaine-induced CREB phosphorylation and c-Fos expression are suppressed in Parkinsonism model mice. Kano, T., Suzuki, Y., Shibuya, M., Kiuchi, K., Hagiwara, M. Neuroreport (1995) [Pubmed]
  18. Mechanism of secalonic acid D-induced inhibition of transcription factor binding to cyclic AMP response element in the developing murine palate. Hanumegowda, U.M., Dhulipala, V.C., Reddy, C.S. Toxicol. Sci. (2002) [Pubmed]
  19. Transcriptional effects of estrogen on neuronal neurotensin gene expression involve cAMP/protein kinase A-dependent signaling mechanisms. Watters, J.J., Dorsa, D.M. J. Neurosci. (1998) [Pubmed]
  20. Defective thymocyte proliferation and IL-2 production in transgenic mice expressing a dominant-negative form of CREB. Barton, K., Muthusamy, N., Chanyangam, M., Fischer, C., Clendenin, C., Leiden, J.M. Nature (1996) [Pubmed]
  21. Action potential-dependent regulation of gene expression: temporal specificity in ca2+, cAMP-responsive element binding proteins, and mitogen-activated protein kinase signaling. Fields, R.D., Eshete, F., Stevens, B., Itoh, K. J. Neurosci. (1997) [Pubmed]
  22. Induction of COX-2 by LPS in macrophages is regulated by Tpl2-dependent CREB activation signals. Eliopoulos, A.G., Dumitru, C.D., Wang, C.C., Cho, J., Tsichlis, P.N. EMBO J. (2002) [Pubmed]
  23. Impaired proliferation and survival of activated B cells in transgenic mice that express a dominant-negative cAMP-response element-binding protein transcription factor in B cells. Zhang, C.Y., Wu, Y.L., Boxer, L.M. J. Biol. Chem. (2002) [Pubmed]
  24. Cytokine-mediated down-regulation of the transcription factor cAMP-response element-binding protein in pancreatic beta-cells. Jambal, P., Masterson, S., Nesterova, A., Bouchard, R., Bergman, B., Hutton, J.C., Boxer, L.M., Reusch, J.E., Pugazhenthi, S. J. Biol. Chem. (2003) [Pubmed]
  25. Fluid shear stress-induced cyclooxygenase-2 expression is mediated by C/EBP beta, cAMP-response element-binding protein, and AP-1 in osteoblastic MC3T3-E1 cells. Ogasawara, A., Arakawa, T., Kaneda, T., Takuma, T., Sato, T., Kaneko, H., Kumegawa, M., Hakeda, Y. J. Biol. Chem. (2001) [Pubmed]
  26. Transcriptional regulation of basal cyclooxygenase-2 expression in murine lung tumor-derived cell lines by CCAAT/enhancer-binding protein and activating transcription factor/cAMP response element-binding protein. Wardlaw, S.A., Zhang, N., Belinsky, S.A. Mol. Pharmacol. (2002) [Pubmed]
  27. Importance of cAMP-response element-binding protein in regulation of expression of the murine cyclic nucleotide phosphodiesterase 3B (Pde3b) gene in differentiating 3T3-L1 preadipocytes. Liu, H., Tang, J.R., Choi, Y.H., Napolitano, M., Hockman, S., Taira, M., Degerman, E., Manganiello, V.C. J. Biol. Chem. (2006) [Pubmed]
  28. Modulation of pro-survival Akt/protein kinase B and ERK1/2 signaling cascades by quercetin and its in vivo metabolites underlie their action on neuronal viability. Spencer, J.P., Rice-Evans, C., Williams, R.J. J. Biol. Chem. (2003) [Pubmed]
  29. Individual CREB-target genes dictate usage of distinct cAMP-responsive coactivation mechanisms. Xu, W., Kasper, L.H., Lerach, S., Jeevan, T., Brindle, P.K. EMBO J. (2007) [Pubmed]
  30. Isolation and characterization of nuclear proteins that bind to T cell receptor V beta decamer motif. Lee, M.R., Chung, C.S., Liou, M.L., Wu, M., Li, W.F., Hsueh, Y.P., Lai, M.Z. J. Immunol. (1992) [Pubmed]
  31. Hydrogen peroxide-mediated phosphorylation of ERK1/2, Akt/PKB and JNK in cortical neurones: dependence on Ca(2+) and PI3-kinase. Crossthwaite, A.J., Hasan, S., Williams, R.J. J. Neurochem. (2002) [Pubmed]
  32. Cyclic adenosine 3',5'-monophosphate (cAMP) enhances cAMP-responsive element binding (CREB) protein phosphorylation and phospho-CREB interaction with the mouse steroidogenic acute regulatory protein gene promoter. Clem, B.F., Hudson, E.A., Clark, B.J. Endocrinology (2005) [Pubmed]
  33. Overexpression and ribozyme-mediated targeting of transcriptional coactivators CREB-binding protein and p300 revealed their indispensable roles in adipocyte differentiation through the regulation of peroxisome proliferator-activated receptor gamma. Takahashi, N., Kawada, T., Yamamoto, T., Goto, T., Taimatsu, A., Aoki, N., Kawasaki, H., Taira, K., Yokoyama, K.K., Kamei, Y., Fushiki, T. J. Biol. Chem. (2002) [Pubmed]
  34. 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]
  35. Regulation of cyclin D1 and Wnt10b gene expression by cAMP-responsive element-binding protein during early adipogenesis involves differential promoter methylation. Fox, K.E., Colton, L.A., Erickson, P.F., Friedman, J.E., Cha, H.C., Keller, P., MacDougald, O.A., Klemm, D.J. J. Biol. Chem. (2008) [Pubmed]
  36. MSKs are required for the transcription of the nuclear orphan receptors Nur77, Nurr1 and Nor1 downstream of MAPK signalling. Darragh, J., Soloaga, A., Beardmore, V.A., Wingate, A.D., Wiggin, G.R., Peggie, M., Arthur, J.S. Biochem. J. (2005) [Pubmed]
  37. Genetic alteration of anxiety and stress-like behavior in mice lacking CaMKIV. Shum, F.W., Ko, S.W., Lee, Y.S., Kaang, B.K., Zhuo, M. Molecular pain [electronic resource] (2005) [Pubmed]
  38. ACTH 1-24 inhibits proliferation of adrenocortical tumors in vivo. Zwermann, O., Schulte, D.M., Reincke, M., Beuschlein, F. Eur. J. Endocrinol. (2005) [Pubmed]
  39. Macrophage inflammatory protein 2 inhibits beta-amyloid peptide (1-42)-mediated hippocampal neuronal apoptosis through activation of mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling pathways. Watson, K., Fan, G.H. Mol. Pharmacol. (2005) [Pubmed]
  40. B cell receptor-induced cAMP-response element-binding protein activation in B lymphocytes requires novel protein kinase Cdelta. Blois, J.T., Mataraza, J.M., Mecklenbraüker, I., Tarakhovsky, A., Chiles, T.C. J. Biol. Chem. (2004) [Pubmed]
  41. Colocalization of phosphorylated CREB with calcium/calmodulin-dependent protein kinase IV in hippocampal neurons induced by ohmfentanyl stereoisomers. Gao, C., Chen, L., Tao, Y., Chen, J., Xu, X., Zhang, G., Chi, Z. Brain Res. (2004) [Pubmed]
  42. Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit tumor necrosis factor alpha transcriptional activation by regulating nuclear factor-kB and cAMP response element-binding protein/c-Jun. Delgado, M., Munoz-Elias, E.J., Kan, Y., Gozes, I., Fridkin, M., Brenneman, D.E., Gomariz, R.P., Ganea, D. J. Biol. Chem. (1998) [Pubmed]
  43. Regulation of steroidogenesis and the steroidogenic acute regulatory protein by a member of the cAMP response-element binding protein family. Manna, P.R., Dyson, M.T., Eubank, D.W., Clark, B.J., Lalli, E., Sassone-Corsi, P., Zeleznik, A.J., Stocco, D.M. Mol. Endocrinol. (2002) [Pubmed]
  44. Up-regulated phosphorylation of signal transducer and activator of transcription 3 and cyclic AMP-responsive element binding protein by peripheral inflammation in primary afferent neurons possibly through oncostatin M receptor. Tamura, S., Morikawa, Y., Senba, E. Neuroscience (2005) [Pubmed]
  45. Impaired synaptic plasticity and cAMP response element-binding protein activation in Ca2+/calmodulin-dependent protein kinase type IV/Gr-deficient mice. Ho, N., Liauw, J.A., Blaeser, F., Wei, F., Hanissian, S., Muglia, L.M., Wozniak, D.F., Nardi, A., Arvin, K.L., Holtzman, D.M., Linden, D.J., Zhuo, M., Muglia, L.J., Chatila, T.A. J. Neurosci. (2000) [Pubmed]
  46. Quantitative trait loci affecting initial sensitivity and acute functional tolerance to ethanol-induced ataxia and brain cAMP signaling in BXD recombinant inbred mice. Kirstein, S.L., Davidson, K.L., Ehringer, M.A., Sikela, J.M., Erwin, V.G., Tabakoff, B. J. Pharmacol. Exp. Ther. (2002) [Pubmed]
  47. Targeted mutation of the CREB gene: compensation within the CREB/ATF family of transcription factors. Hummler, E., Cole, T.J., Blendy, J.A., Ganss, R., Aguzzi, A., Schmid, W., Beermann, F., Schütz, G. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  48. Role of AP-1 in ethanol-induced N-methyl-D-aspartate receptor 2B subunit gene up-regulation in mouse cortical neurons. Qiang, M., Ticku, M.K. J. Neurochem. (2005) [Pubmed]
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