The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Crebbp  -  CREB binding protein

Rattus norvegicus

Synonyms: CBP, CREB-binding protein, Cbp, RSTS, RTS
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Crebbp

  • The first demonstration of age-related decreases in CBP expression in the cerebral cortex and hippocampus may provide useful data for investigating the pathogenesis of age-related neurodegenerative diseases and depression [1].
  • Furthermore, we show that overexpression of CBP or p300 can induce hypertrophy and that this effect requires their histone acetyltransferase (HAT) activity [2].
  • The transcriptional co-activators CREB-binding protein (CBP) and p300 play a critical role in cardiac hypertrophy that is dependent on their histone acetyltransferase activity [2].
  • This selective degradation of CBP was absent in spinocerebellar ataxia 3 [3].
  • An intact proximal element plus the TATA box gave almost full transcriptional activity in transient transfection experiments and only in differentiated hepatoma cells of line H4II, whereas the distal elements (distal element III [DEIII], the NF1-binding site DEII, and the E/CBP-binding site DEI) had become essentially dispensable [4].

High impact information on Crebbp

  • 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 [5].
  • A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors [5].
  • FGF2 facilitates access of the STAT/CBP (signal transducer and activator of transcription/CRE binding protein) complex to the GFAP promoter by inducing Lys4 methylation and suppressing Lys9 methylation of histone H3 at the STAT binding site [6].
  • Regulation of CBP-mediated transcription by neuronal calcium signaling [7].
  • These observations indicate that CBP can function as a calcium-sensitive transcriptional coactivator that may act as a regulatory switch for glutamate-induced CREB-mediated transcription [7].

Chemical compound and disease context of Crebbp


Biological context of Crebbp


Anatomical context of Crebbp

  • CBP immunoreactivity was significantly deceased in the pyramidal layer of CA1-3 regions in aged hippocampus [1].
  • In the cerebral cortex, the distribution patterns were not different between adult and aged groups, but the staining intensity of CBP was significantly decreased in aged rats [1].
  • Expression level of CBP mRNA was relatively low in the small intestine, while p300 mRNA was ubiquitously expressed in various tissues including the small intestine in the rat [12].
  • The expression levels of CBP and p300 were high in fetal hepatocytes, but low in adult ones [13].
  • To examine the functional role of CBP, we infused oligodeoxynucleotides that were antisense to CBP mRNA or a scrambled sequence as a control into the hypothalamus of female rats on postnatal d 0, 1, and 2 [14].

Associations of Crebbp with chemical compounds


Physical interactions of Crebbp

  • As Ser142 is located within the region of CREB that interacts with CBP, it seemed quite likely that mutations at this site might interfere with binding to CBP [18].
  • It has been reported that the mitogen-activated protein (MAP) kinase pathway inhibits PPAR-gamma function through its phosphorylation, and co-activator CREB-binding protein (CBP)/p300 interacts with PPAR-gamma and modulates its activity [19].
  • Mutant huntingtin bound much stronger to CBP than normal huntingtin, possibly contributing to repression [3].

Regulatory relationships of Crebbp

  • Mutant huntingtin represses CBP, but not p300, by binding and protein degradation [3].

Other interactions of Crebbp

  • The MAP kinase pathway and CBP may thus antagonize against PPAR-gamma in AT1R gene transcription, probably leading to the progression of atherosclerosis [19].
  • Thus, mutant huntingtin specifically affects CBP and not p300 both at the early and later time points, via multiple mechanisms [3].
  • We conclude that E2beta inhibits hypoxic induction of ET-1 gene expression by interfering with HIF activity, possibly through competition for limiting quantities of CBP/p300 [20].
  • On the other hand, both the basal and PKA-induced activities were elevated by overexpression of Sp1, its effect on PKA-induced activity being more pronounced with coexpression of CBP and repressed by E1A oncoprotein [21].
  • Coactivators p300/CBP are at least partially responsible for the enhanced activation mediated by c-Rel and PKA-Cbeta [22].

Analytical, diagnostic and therapeutic context of Crebbp


  1. Age-related changes in CREB binding protein immunoreactivity in the cerebral cortex and hippocampus of rats. Chung, Y.H., Kim, E.J., Shin, C.M., Joo, K.M., Kim, M.J., Woo, H.W., Cha, C.I. Brain Res. (2002) [Pubmed]
  2. The transcriptional co-activators CREB-binding protein (CBP) and p300 play a critical role in cardiac hypertrophy that is dependent on their histone acetyltransferase activity. Gusterson, R.J., Jazrawi, E., Adcock, I.M., Latchman, D.S. J. Biol. Chem. (2003) [Pubmed]
  3. Mutant huntingtin represses CBP, but not p300, by binding and protein degradation. Cong, S.Y., Pepers, B.A., Evert, B.O., Rubinsztein, D.C., Roos, R.A., van Ommen, G.J., Dorsman, J.C. Mol. Cell. Neurosci. (2005) [Pubmed]
  4. The rat albumin promoter: cooperation with upstream elements is required when binding of APF/HNF1 to the proximal element is partially impaired by mutation or bacterial methylation. Tronche, F., Rollier, A., Bach, I., Weiss, M.C., Yaniv, M. Mol. Cell. Biol. (1989) [Pubmed]
  5. 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]
  6. FGF2-induced chromatin remodeling regulates CNTF-mediated gene expression and astrocyte differentiation. Song, M.R., Ghosh, A. Nat. Neurosci. (2004) [Pubmed]
  7. Regulation of CBP-mediated transcription by neuronal calcium signaling. Hu, S.C., Chrivia, J., Ghosh, A. Neuron (1999) [Pubmed]
  8. Cyclic AMP response element binding protein (CREB) and CREB binding protein (CBP) in global cerebral ischemia. Jin, K., Mao, X.O., Simon, R.P., Greenberg, D.A. J. Mol. Neurosci. (2001) [Pubmed]
  9. Growth and metabolic parameters in pups of undernourished lactating rats. Boxwell, J., Ayson, P., Ramenofsky, M. Physiol. Behav. (1995) [Pubmed]
  10. 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]
  11. Nuclear receptor coactivators modulate hormone-dependent gene expression in brain and female reproductive behavior in rats. Molenda, H.A., Griffin, A.L., Auger, A.P., McCarthy, M.M., Tetel, M.J. Endocrinology (2002) [Pubmed]
  12. Major intestinal coactivator p300 strongly activates peroxisome proliferator-activated receptor in intestinal cell line, Caco-2. Mochizuki, K., Suruga, K., Sakaguchi, N., Takase, S., Goda, T. Gene (2002) [Pubmed]
  13. Transcriptional coactivators CBP and p300 cooperatively enhance HNF-1alpha-mediated expression of the albumin gene in hepatocytes. Dohda, T., Kaneoka, H., Inayoshi, Y., Kamihira, M., Miyake, K., Iijima, S. J. Biochem. (2004) [Pubmed]
  14. Expression of the nuclear receptor coactivator, cAMP response element-binding protein, is sexually dimorphic and modulates sexual differentiation of neonatal rat brain. Auger, A.P., Perrot-Sinal, T.S., Auger, C.J., Ekas, L.A., Tetel, M.J., McCarthy, M.M. Endocrinology (2002) [Pubmed]
  15. A transcriptional switch mediated by cofactor methylation. Xu, W., Chen, H., Du, K., Asahara, H., Tini, M., Emerson, B.M., Montminy, M., Evans, R.M. Science (2001) [Pubmed]
  16. Morphological plasticity of dendritic spines in central neurons is mediated by activation of cAMP response element binding protein. Murphy, D.D., Segal, M. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  17. Characterization of a CREB gain-of-function mutant with constitutive transcriptional activity in vivo. Du, K., Asahara, H., Jhala, U.S., Wagner, B.L., Montminy, M. Mol. Cell. Biol. (2000) [Pubmed]
  18. An inactivating point mutation demonstrates that interaction of cAMP response element binding protein (CREB) with the CREB binding protein is not sufficient for transcriptional activation. Sun, P., Maurer, R.A. J. Biol. Chem. (1995) [Pubmed]
  19. Effects of mitogen-activated protein kinase pathway and co-activator CREP-binding protein on peroxisome proliferator-activated receptor-gamma-mediated transcription suppression of angiotensin II type 1 receptor gene. Sugawara, A., Takeuchi, K., Uruno, A., Kudo, M., Sato, K., Ito, S. Hypertens. Res. (2003) [Pubmed]
  20. Estradiol attenuates hypoxia-induced pulmonary endothelin-1 gene expression. Earley, S., Resta, T.C. Am. J. Physiol. Lung Cell Mol. Physiol. (2002) [Pubmed]
  21. The role of Sp1 and AP-2 in basal and protein kinase A--induced expression of mitochondrial serine:pyruvate aminotransferase in hepatocytes. Uchida, C., Oda, T., Sugiyama, T., Otani, S., Kitagawa, M., Ichiyama, A. J. Biol. Chem. (2002) [Pubmed]
  22. Stimulation of c-Rel transcriptional activity by PKA catalytic subunit beta. Yu, S.H., Chiang, W.C., Shih, H.M., Wu, K.J. J. Mol. Med. (2004) [Pubmed]
  23. Assignment of the rat Crebbp and Rxrip13 genes to chromosome bands 10q12-->q21 and 10q24 respectively by in situ hybridization. Van Reeth, T., Van Vooren, P., Szpirer, C., Szpirer, J. Cytogenet. Cell Genet. (1999) [Pubmed]
WikiGenes - Universities