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Gene Review

Crebbp  -  CREB binding protein

Mus musculus

Synonyms: AW558298, CBP, CBP/p300, CREB-binding protein, Cbp, ...
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Disease relevance of Crebbp

  • Increased insulin sensitivity despite lipodystrophy in Crebbp heterozygous mice [1].
  • Expression of a conditional form of adenovirus E1A in murine erythroleukemia cells blocks differentiation and expression of endogenous GATA-1 target genes, whereas mutant forms of E1A unable to bind CBP/p300 have no effect [2].
  • Thus, although the CBP SID domain adopts a similar fold in complex with different p160 proteins, the topologies of the AD1 domains are strikingly different, a feature that is likely to contribute to functional specificity of these coactivator complexes [3].
  • Rubinstein-Taybi syndrome (RTS), which is an autosomal dominant syndrome characterized by abnormal pattern formation, is associated with mutations in the human CBP gene [4].
  • Extensive brain hemorrhage and embryonic lethality in a mouse null mutant of CREB-binding protein [4].

Psychiatry related information on Crebbp


High impact information on Crebbp


Chemical compound and disease context of Crebbp


Biological context of Crebbp

  • CBP enhances transcriptional activities via histone acetylation and the recruitment of additional co-activators such as SRC (steroid coactivator)-1 (ref. 9). To identify its physiological functions using a loss-of-function mutant, we analyzed CBP-deficient mice [1].
  • Here we show that the protein-binding KIX domains of CBP and p300 have nonredundant functions in mice [10].
  • Interaction mapping pinpoints contact sites to the zinc finger region of GATA-1 and to the E1A-binding region of CBP [2].
  • We report here that CBP markedly stimulates GATA-1's transcriptional activity in transient transfection experiments in nonhematopoietic cells [2].
  • To elucidate the importance of the cAMP-PKA-CREB-CBP pathway in pancreatic beta cells specifically at the nuclear level, we have examined mutant mice lacking the insulin-dependent phosphorylation site of CBP [11].

Anatomical context of Crebbp


Associations of Crebbp with chemical compounds

  • In these mice, the CREB-CBP interaction is enhanced in both the absence and presence of cAMP stimulation [11].
  • CBP, but not p300, is phosphorylated at serine 436 in response to insulin action [11].
  • Mouse p53 is acetylated at lysine 317 by PCAF and at multiple lysine residues at the extreme carboxyl terminus by CBP/p300 in response to genotoxic and some nongenotoxic stresses [16].
  • In these beta cells, however, glucose-stimulated insulin secretion was diminished, resulting from concomitant CREB-CBP-mediated pgc1a gene activation [11].
  • Expression of aP2 and LPL genes, as well as glycerol-3-phosphate dehydrogenase activity and triacylglyceride accumulation after adipogenic induction, was largely suppressed in 3T3-L1 adipocytes expressing either the CBP- or p300-specific active ribozyme, but not in inactive ribozyme-expressing cells [12].

Physical interactions of Crebbp


Enzymatic interactions of Crebbp

  • We used mice carrying p300flox and a CBP conditional knockout allele (CBPflox) in conjunction with an Lck-Cre transgene to delete CBP and p300 starting at the CD4- CD8- double-negative thymocyte stage of T-cell development [20].

Regulatory relationships of Crebbp

  • These results suggest that p300/CBP is a critical control point in NF-kappaB-dependent transcriptional regulation of cytoprotective genes by cytokines [21].
  • A mutant CBP lacking the N terminus failed to stimulate p53-dependent transactivation [22].
  • Prevention of PU.1-induced growth inhibition and apoptosis but not differentiation block in murine erythroleukemia cells by overexpression of CBP [23].
  • In the absence of Wnt signaling, LEF-1/TCF proteins repress transcription in association with Groucho and CBP [24].
  • These results indicate that the constitutive and inducible activation properties of c-Myb and CREB reflect secondary structural characteristics of their corresponding activating regions that influence the thermodynamics of formation of a complex with CBP [25].

Other interactions of Crebbp


Analytical, diagnostic and therapeutic context of Crebbp

  • Sequence analysis reveals that both zones are well conserved in all vertebrate p300/CBP proteins, suggesting their functional importance [30].
  • Furthermore, by interaction studies in vivo (a mammalian two-hybrid assay) and in vitro (a pulldown assay), p300/CBP was found to directly bind CRX through their C-terminal domains [31].
  • Microinjection of p300/CBP antibodies into myoblasts blocks terminal differentiation, cell fusion, and transcriptional activity of myogenic bHLH proteins [32].
  • Also found at the array by immunofluorescence were two different steroid receptor coactivators (SRC1 and CBP) with acetyltransferase activity, a chromatin remodeler (BRG1), and two transcription factors (NFI and AP-2) [33].
  • Co-immunoprecipitation experiments using cell extracts showed that p67(SRF) could be retained with antibodies directed against the CREB-binding protein, suggesting that the two proteins form a multimolecular complex in live cells [34].


  1. Increased insulin sensitivity despite lipodystrophy in Crebbp heterozygous mice. Yamauchi, T., Oike, Y., Kamon, J., Waki, H., Komeda, K., Tsuchida, A., Date, Y., Li, M.X., Miki, H., Akanuma, Y., Nagai, R., Kimura, S., Saheki, T., Nakazato, M., Naitoh, T., Yamamura, K., Kadowaki, T. Nat. Genet. (2002) [Pubmed]
  2. CREB-binding protein cooperates with transcription factor GATA-1 and is required for erythroid differentiation. Blobel, G.A., Nakajima, T., Eckner, R., Montminy, M., Orkin, S.H. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  3. Structural diversity in p160/CREB-binding protein coactivator complexes. Waters, L., Yue, B., Veverka, V., Renshaw, P., Bramham, J., Matsuda, S., Frenkiel, T., Kelly, G., Muskett, F., Carr, M., Heery, D.M. J. Biol. Chem. (2006) [Pubmed]
  4. Extensive brain hemorrhage and embryonic lethality in a mouse null mutant of CREB-binding protein. Tanaka, Y., Naruse, I., Hongo, T., Xu, M., Nakahata, T., Maekawa, T., Ishii, S. Mech. Dev. (2000) [Pubmed]
  5. Developmentally regulated expression of the transcriptional cofactors/histone acetyltransferases CBP and p300 during mouse embryogenesis. Partanen, A., Motoyama, J., Hui, C.C. Int. J. Dev. Biol. (1999) [Pubmed]
  6. CREB-binding protein activation by presenilin 1 but not by its M146L mutant. Francis, Y.I., Stephanou, A., Latchman, D.S. Neuroreport (2006) [Pubmed]
  7. Differential Role for CBP and p300 CREB-Binding Domain in Motor Skill Learning. Oliveira, A.M., Abel, T., Brindle, P.K., Wood, M.A. Behav. Neurosci. (2006) [Pubmed]
  8. Concomitant increase of histone acetyltransferase activity and degradation of p300 during retinoic acid-induced differentiation of F9 cells. Brouillard, F., Cremisi, C.E. J. Biol. Chem. (2003) [Pubmed]
  9. Altered transcription in yeast expressing expanded polyglutamine. Hughes, R.E., Lo, R.S., Davis, C., Strand, A.D., Neal, C.L., Olson, J.M., Fields, S. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  10. A transcription-factor-binding surface of coactivator p300 is required for haematopoiesis. Kasper, L.H., Boussouar, F., Ney, P.A., Jackson, C.W., Rehg, J., van Deursen, J.M., Brindle, P.K. Nature (2002) [Pubmed]
  11. Increased Pancreatic {beta}-Cell Proliferation Mediated by CREB Binding Protein Gene Activation. Hussain, M.A., Porras, D.L., Rowe, M.H., West, J.R., Song, W.J., Schreiber, W.E., Wondisford, F.E. Mol. Cell. Biol. (2006) [Pubmed]
  12. 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]
  13. Differential role of p300 and CBP acetyltransferase during myogenesis: p300 acts upstream of MyoD and Myf5. Roth, J.F., Shikama, N., Henzen, C., Desbaillets, I., Lutz, W., Marino, S., Wittwer, J., Schorle, H., Gassmann, M., Eckner, R. EMBO J. (2003) [Pubmed]
  14. Essential function of p300 acetyltransferase activity in heart, lung and small intestine formation. Shikama, N., Lutz, W., Kretzschmar, R., Sauter, N., Roth, J.F., Marino, S., Wittwer, J., Scheidweiler, A., Eckner, R. EMBO J. (2003) [Pubmed]
  15. Distinct roles for CREB-binding protein and p300 in hematopoietic stem cell self-renewal. Rebel, V.I., Kung, A.L., Tanner, E.A., Yang, H., Bronson, R.T., Livingston, D.M. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  16. Acetylation of mouse p53 at lysine 317 negatively regulates p53 apoptotic activities after DNA damage. Chao, C., Wu, Z., Mazur, S.J., Borges, H., Rossi, M., Lin, T., Wang, J.Y., Anderson, C.W., Appella, E., Xu, Y. Mol. Cell. Biol. (2006) [Pubmed]
  17. Mechanism of action of a distal NF-kappaB-dependent enhancer. Teferedegne, B., Green, M.R., Guo, Z., Boss, J.M. Mol. Cell. Biol. (2006) [Pubmed]
  18. A 36-amino-acid region of CIITA is an effective inhibitor of CBP: novel mechanism of gamma interferon-mediated suppression of collagen alpha(2)(I) and other promoters. Zhu, X.S., Ting, J.P. Mol. Cell. Biol. (2001) [Pubmed]
  19. Ets1 is required for p53 transcriptional activity in UV-induced apoptosis in embryonic stem cells. Xu, D., Wilson, T.J., Chan, D., De Luca, E., Zhou, J., Hertzog, P.J., Kola, I. EMBO J. (2002) [Pubmed]
  20. Conditional knockout mice reveal distinct functions for the global transcriptional coactivators CBP and p300 in T-cell development. Kasper, L.H., Fukuyama, T., Biesen, M.A., Boussouar, F., Tong, C., de Pauw, A., Murray, P.J., van Deursen, J.M., Brindle, P.K. Mol. Cell. Biol. (2006) [Pubmed]
  21. Coordinate inhibition of cytokine-mediated induction of ferritin H, manganese superoxide dismutase, and interleukin-6 by the adenovirus E1A oncogene. Jennings-Gee, J.E., Tsuji, Y., Pietsch, E.C., Moran, E., Mymryk, J.S., Torti, F.M., Torti, S.V. J. Biol. Chem. (2006) [Pubmed]
  22. Murine double minute (MDM2) blocks p53-coactivator interaction, a new mechanism for inhibition of p53-dependent gene expression. Wadgaonkar, R., Collins, T. J. Biol. Chem. (1999) [Pubmed]
  23. Prevention of PU.1-induced growth inhibition and apoptosis but not differentiation block in murine erythroleukemia cells by overexpression of CBP. Manabe, N., Yamamoto, H., Yamada, T., Kihara-Negishi, F., Hashimoto, Y., Mochizuki, M., Oikawa, T. Int. J. Oncol. (2003) [Pubmed]
  24. Regulation of LEF-1/TCF transcription factors by Wnt and other signals. Eastman, Q., Grosschedl, R. Curr. Opin. Cell Biol. (1999) [Pubmed]
  25. Role of secondary structure in discrimination between constitutive and inducible activators. Parker, D., Rivera, M., Zor, T., Henrion-Caude, A., Radhakrishnan, I., Kumar, A., Shapiro, L.H., Wright, P.E., Montminy, M., Brindle, P.K. Mol. Cell. Biol. (1999) [Pubmed]
  26. Loss of Gcn5l2 leads to increased apoptosis and mesodermal defects during mouse development. Xu, W., Edmondson, D.G., Evrard, Y.A., Wakamiya, M., Behringer, R.R., Roth, S.Y. Nat. Genet. (2000) [Pubmed]
  27. Physical and functional interactions between the transcription factor PU.1 and the coactivator CBP. Yamamoto, H., Kihara-Negishi, F., Yamada, T., Hashimoto, Y., Oikawa, T. Oncogene (1999) [Pubmed]
  28. 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]
  29. Vitamin A depletion is associated with low phosphoenolpyruvate carboxykinase mRNA levels during late fetal development and at birth in mice. Ghoshal, S., Pasham, S., Odom, D.P., Furr, H.C., McGrane, M.M. J. Nutr. (2003) [Pubmed]
  30. Biochemical and NMR mapping of the interface between CREB-binding protein and ligand binding domains of nuclear receptor: beyond the LXXLL motif. Klein, F.A., Atkinson, R.A., Potier, N., Moras, D., Cavarelli, J. J. Biol. Chem. (2005) [Pubmed]
  31. p300/CBP acts as a coactivator of the cone-rod homeobox transcription factor. Yanagi, Y., Masuhiro, Y., Mori, M., Yanagisawa, J., Kato, S. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  32. Interaction and functional collaboration of p300/CBP and bHLH proteins in muscle and B-cell differentiation. Eckner, R., Yao, T.P., Oldread, E., Livingston, D.M. Genes Dev. (1996) [Pubmed]
  33. Large-scale chromatin decondensation and recondensation regulated by transcription from a natural promoter. Müller, W.G., Walker, D., Hager, G.L., McNally, J.G. J. Cell Biol. (2001) [Pubmed]
  34. The CREB-binding protein (CBP) cooperates with the serum response factor for transactivation of the c-fos serum response element. Ramirez, S., Ait-Si-Ali, S., Robin, P., Trouche, D., Harel-Bellan, A., Ait Si Ali, S. J. Biol. Chem. (1997) [Pubmed]
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