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Gene Review

CTBP1  -  C-terminal binding protein 1

Homo sapiens

Synonyms: BARS, C-terminal-binding protein 1, CTBP, CtBP1
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Disease relevance of CTBP1

  • To identify the components of the CtBP corepressor complex, we isolated CtBP-containing protein complexes from the nuclear extracts prepared from HeLa cells infected with adenovirus vectors that expresses hCtBP1 [1].
  • The expression levels of the transcriptional regulators p300 and CtBP modulate the correlations between SNAIL, ZEB1, E-cadherin and vitamin D receptor in human colon carcinomas [2].
  • We conclude that, in addition to regulating the stability of beta-cat, APC facilitates CtBP-mediated repression of Wnt target genes in normal, but not in colorectal cancer cells [3].
  • In this study, we found that hypoxia increased free NADH levels in cancer cells, promoting CtBP recruitment to the E-cadherin promoter [4].
  • This region of E1A binds with a cellular phosphoprotein, CtBP, through a 5-amino acid motif, PLDLS, conserved among the E1A proteins of human adenoviruses [5].

Psychiatry related information on CTBP1

  • The House and Brackmann scale was used for grading facial function and the Brackmann and Bars scale was used for self-assessment of facial function [6].

High impact information on CTBP1

  • However, Pc2 dramatically enhances CtBP sumoylation [7].
  • Homeodomain interacting protein kinase 2 promotes apoptosis by downregulating the transcriptional corepressor CtBP [8].
  • Genetic knockout of the transcriptional corepressor CtBP in mouse embryo fibroblasts upregulates several genes involved in apoptosis [8].
  • We show that CtBP is sumoylated at a single lysine [7].
  • Inhibiting the expression of CtBP and its associated histone-modifying activities by RNA-mediated interference resulted in alterations of histone modifications at the promoter of the tumour invasion suppressor gene E-cadherin and increased promoter activity in a reporter assay [9].

Chemical compound and disease context of CTBP1


Biological context of CTBP1

  • In the mouse, CtBP1 is expressed from embryo to adult, but CtBP2 is mainly expressed during embryogenesis [11].
  • By utilizing in vitro pull-down assays, in vivo interaction studies, and immunofluorescence in combination with overexpression and RNA interference experiments, we present evidence that Pnn interacts with the known transcriptional corepressor CtBP1 [12].
  • Finally, we show that the interaction between AME and CtBP1 is biologically important and is necessary for growth upregulation and abnormal differentiation of the murine hematopoietic precursor cell line 32Dc13 and of murine bone marrow progenitors [13].
  • By using reporter gene assays, we demonstrate that AME represses gene transcription by CtBP1-dependent and CtBP1-independent mechanisms [13].
  • CtBP is a corepressor of transcription that acts by inhibiting coactivators and recruiting to promoter control elements (via interactions with DNA-binding transcription factors) a complex of proteins that modify histones, repress transcription and silence gene expression [14].

Anatomical context of CTBP1

  • Remarkably, their high expression occurs in subsets of deltaEF1-expressing tissues, e.g., cephalic and dorsal root ganglia, spinal cord, posterior-distal halves of the limb bud mesenchyme, and perichondrium of forming digits, supporting the conclusion that CtBP1 and -2 play crucial roles in the repressor action of deltaEF1 in these tissues [11].
  • Although there are some reports of CtBP with a cytoplasmic distribution after transfection, it is unclear how in normal cells a nuclear corepressor regulates the behavior of the Golgi complex at the onset of mitosis [14].
  • The transcriptional co-repressor C-terminal binding protein (CtBP) associates with centrosomes during mitosis [14].
  • For instance, Ctbp1 is predominantly expressed in the epiblast, whereas Ctbp2 is in the primitive streak at HH stage 3 [15].
  • Similarly, although both genes display similar expression patterns in early somitogenesis, in mature somites, Ctbp1 transcripts are located in myotomal cells, whereas Ctbp2 transcripts are observed in dermomyotomal cells [15].

Associations of CTBP1 with chemical compounds


Physical interactions of CTBP1

  • Additionally, E1A also displaced the histone methyltransferase G9a and the E-box repressor ZEB from the CtBP2 complex through the C-terminal CtBP-binding domain [22].
  • Corepressor CtBP1 interacts with and specifically inhibits CBP activity [23].
  • Furthermore, we show that full RIP140 corepressor activity is contributed both by C-terminal receptor-binding LXXLL motifs and interaction with the CtBP corepressor [24].
  • The brain-specific actin-related protein ArpN alpha interacts with the transcriptional co-repressor CtBP [25].
  • Mutation of the CtBP binding site on Pc2 abolishes E3 activity toward CtBP [26].

Enzymatic interactions of CTBP1


Regulatory relationships of CTBP1

  • Consistent with a change in localization, the K428R mutation abolished the ability of CtBP1 to repress the E-cadherin promoter activity [27].
  • CtBP interacts with Sin3A but not with the Mi-2 co-repressor and it represses transcription in a manner that is independent of histone deacetylase activity [28].
  • Our previous studies indicate that HIPK2 participates in a pathway of UV-triggered CtBP clearance that results in cell death [18].
  • A novel GATA factor transcriptionally represses yolk protein precursor genes in the mosquito Aedes aegypti via interaction with the CtBP corepressor [20].

Other interactions of CTBP1

  • As expected from the corepressor activity of CtBP, this mutation also impairs the HIC1-mediated transcriptional repression [29].
  • CtBP2, a close homolog of CtBP1, lacked the SUMOylation site and was not modified by SUMO-1 [27].
  • As a consequence of this interaction Pnn was capable of relieving the CtBP1-mediated repression of E-cadherin promoter activity [12].
  • To date, a single 48-kDa protein, CTBP1, has been shown to associate with this region [30].
  • CtIP was recently identified as a protein that associates with BRCA1 and two other nuclear factors, CtBP1 and Rb1 [31].

Analytical, diagnostic and therapeutic context of CTBP1

  • Using different approaches (titration of endogenous CtBPs, mutagenesis and transfection in CtBP knock-out cells), we find that recruitment of CtBPs only partially explains the negative regulation exerted by RIP140 [32].
  • Using polyclonal rabbit antibodies that were raised against a human CtBP1-GST fusion-protein, here we show by immunofluorescence laser-scanning confocal microscopy that in mitotic cells a species of CtBP becomes associated with the centrosomes at the onset of prophase and then throughout mitosis [14].
  • The mRNA expression levels of SNAIL and ZEB1, and of transcriptional regulators p300 and CtBP, were measured by RT-PCR in tumor and normal tissue from 101 colon carcinoma patients [2].
  • We have cloned the avian orthologues of Ctbp1 and Ctbp2 and examined their expression pattern by whole-mount in situ hybridization between Hamburger and Hamilton (HH) stages 3 and 24 [15].
  • Here we report the identification of a CtBP complex that contains the essential components for both gene targeting and coordinated histone modifications, allowing for the effective repression of genes targeted by CtBP [9].


  1. Association of class I histone deacetylases with transcriptional corepressor CtBP. Subramanian, T., Chinnadurai, G. FEBS Lett. (2003) [Pubmed]
  2. The expression levels of the transcriptional regulators p300 and CtBP modulate the correlations between SNAIL, ZEB1, E-cadherin and vitamin D receptor in human colon carcinomas. Peña, C., García, J.M., García, V., Silva, J., Domínguez, G., Rodríguez, R., Maximiano, C., García de Herreros, A., Muñoz, A., Bonilla, F. Int. J. Cancer (2006) [Pubmed]
  3. The APC tumor suppressor counteracts beta-catenin activation and H3K4 methylation at Wnt target genes. Sierra, J., Yoshida, T., Joazeiro, C.A., Jones, K.A. Genes Dev. (2006) [Pubmed]
  4. Redox sensor CtBP mediates hypoxia-induced tumor cell migration. Zhang, Q., Wang, S.Y., Nottke, A.C., Rocheleau, J.V., Piston, D.W., Goodman, R.H. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  5. Interaction between a cellular protein that binds to the C-terminal region of adenovirus E1A (CtBP) and a novel cellular protein is disrupted by E1A through a conserved PLDLS motif. Schaeper, U., Subramanian, T., Lim, L., Boyd, J.M., Chinnadurai, G. J. Biol. Chem. (1998) [Pubmed]
  6. Evaluation of quality of life and symptoms after translabyrinthine acoustic neuroma surgery. Andersson, G., Ekvall, L., Kinnefors, A., Nyberg, G., Rask-Andersen, H. The American journal of otology. (1997) [Pubmed]
  7. The polycomb protein Pc2 is a SUMO E3. Kagey, M.H., Melhuish, T.A., Wotton, D. Cell (2003) [Pubmed]
  8. Homeodomain interacting protein kinase 2 promotes apoptosis by downregulating the transcriptional corepressor CtBP. Zhang, Q., Yoshimatsu, Y., Hildebrand, J., Frisch, S.M., Goodman, R.H. Cell (2003) [Pubmed]
  9. Coordinated histone modifications mediated by a CtBP co-repressor complex. Shi, Y., Sawada, J., Sui, G., Affar, e.l. .B., Whetstine, J.R., Lan, F., Ogawa, H., Luke, M.P., Nakatani, Y., Shi, Y. Nature (2003) [Pubmed]
  10. Acetylation at a lysine residue adjacent to the CtBP binding motif within adenovirus 12 E1A causes structural disruption and limited reduction of CtBP binding. Molloy, D., Mapp, K.L., Webster, R., Gallimore, P.H., Grand, R.J. Virology (2006) [Pubmed]
  11. Identification of CtBP1 and CtBP2 as corepressors of zinc finger-homeodomain factor deltaEF1. Furusawa, T., Moribe, H., Kondoh, H., Higashi, Y. Mol. Cell. Biol. (1999) [Pubmed]
  12. Nuclear speckle-associated protein Pnn/DRS binds to the transcriptional corepressor CtBP and relieves CtBP-mediated repression of the E-cadherin gene. Alpatov, R., Munguba, G.C., Caton, P., Joo, J.H., Shi, Y., Shi, Y., Hunt, M.E., Sugrue, S.P. Mol. Cell. Biol. (2004) [Pubmed]
  13. The leukemia-associated transcription repressor AML1/MDS1/EVI1 requires CtBP to induce abnormal growth and differentiation of murine hematopoietic cells. Senyuk, V., Chakraborty, S., Mikhail, F.M., Zhao, R., Chi, Y., Nucifora, G. Oncogene (2002) [Pubmed]
  14. The transcriptional co-repressor C-terminal binding protein (CtBP) associates with centrosomes during mitosis. Spyer, M., Allday, M.J. Cell Cycle (2006) [Pubmed]
  15. Expression of avian C-terminal binding proteins (Ctbp1 and Ctbp2) during embryonic development. Van Hateren, N., Shenton, T., Borycki, A.G. Dev. Dyn. (2006) [Pubmed]
  16. The human candidate tumor suppressor gene HIC1 recruits CtBP through a degenerate GLDLSKK motif. Deltour, S., Pinte, S., Guerardel, C., Wasylyk, B., Leprince, D. Mol. Cell. Biol. (2002) [Pubmed]
  17. Huntingtin is present in the nucleus, interacts with the transcriptional corepressor C-terminal binding protein, and represses transcription. Kegel, K.B., Meloni, A.R., Yi, Y., Kim, Y.J., Doyle, E., Cuiffo, B.G., Sapp, E., Wang, Y., Qin, Z.H., Chen, J.D., Nevins, J.R., Aronin, N., DiFiglia, M. J. Biol. Chem. (2002) [Pubmed]
  18. Homeodomain-interacting protein kinase-2 mediates CtBP phosphorylation and degradation in UV-triggered apoptosis. Zhang, Q., Nottke, A., Goodman, R.H. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  19. Metabolic regulation of SIRT1 transcription via a HIC1:CtBP corepressor complex. Zhang, Q., Wang, S.Y., Fleuriel, C., Leprince, D., Rocheleau, J.V., Piston, D.W., Goodman, R.H. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  20. A novel GATA factor transcriptionally represses yolk protein precursor genes in the mosquito Aedes aegypti via interaction with the CtBP corepressor. Martín, D., Piulachs, M.D., Raikhel, A.S. Mol. Cell. Biol. (2001) [Pubmed]
  21. Phosphorylation of CtBP1 by cAMP-dependent protein kinase modulates induction of CYP17 by stimulating partnering of CtBP1 and 2. Dammer, E.B., Sewer, M.B. J. Biol. Chem. (2008) [Pubmed]
  22. Changes in C-terminal Binding Protein 2 (CtBP2) Corepressor Complex Induced by E1A and Modulation of E1A Transcriptional Activity by CtBP2. Zhao, L.J., Subramanian, T., Chinnadurai, G. J. Biol. Chem. (2006) [Pubmed]
  23. Corepressor CtBP1 interacts with and specifically inhibits CBP activity. Senyuk, V., Sinha, K.K., Nucifora, G. Arch. Biochem. Biophys. (2005) [Pubmed]
  24. Regulation of subnuclear localization is associated with a mechanism for nuclear receptor corepression by RIP140. Tazawa, H., Osman, W., Shoji, Y., Treuter, E., Gustafsson, J.A., Zilliacus, J. Mol. Cell. Biol. (2003) [Pubmed]
  25. The brain-specific actin-related protein ArpN alpha interacts with the transcriptional co-repressor CtBP. Oma, Y., Nishimori, K., Harata, M. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  26. Multiple activities contribute to Pc2 E3 function. Kagey, M.H., Melhuish, T.A., Powers, S.E., Wotton, D. EMBO J. (2005) [Pubmed]
  27. Opposed regulation of corepressor CtBP by SUMOylation and PDZ binding. Lin, X., Sun, B., Liang, M., Liang, Y.Y., Gast, A., Hildebrand, J., Brunicardi, F.C., Melchior, F., Feng, X.H. Mol. Cell (2003) [Pubmed]
  28. Ikaros interactions with CtBP reveal a repression mechanism that is independent of histone deacetylase activity. Koipally, J., Georgopoulos, K. J. Biol. Chem. (2000) [Pubmed]
  29. A L225A substitution in the human tumour suppressor HIC1 abolishes its interaction with the corepressor CtBP. Stankovic-Valentin, N., Verger, A., Deltour-Balerdi, S., Quinlan, K.G., Crossley, M., Leprince, D. FEBS J. (2006) [Pubmed]
  30. A novel C-terminal binding protein (CTBP2) is closely related to CTBP1, an adenovirus E1A-binding protein, and maps to human chromosome 21q21.3. Katsanis, N., Fisher, E.M. Genomics (1998) [Pubmed]
  31. Nuclear localization and cell cycle-specific expression of CtIP, a protein that associates with the BRCA1 tumor suppressor. Yu, X., Baer, R. J. Biol. Chem. (2000) [Pubmed]
  32. Multiple domains of the Receptor-Interacting Protein 140 contribute to transcription inhibition. Castet, A., Boulahtouf, A., Versini, G., Bonnet, S., Augereau, P., Vignon, F., Khochbin, S., Jalaguier, S., Cavaillès, V. Nucleic Acids Res. (2004) [Pubmed]
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