CTBP1

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Identifiers
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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
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C-terminal-binding protein 1 also known as CtBP1 is a protein that in humans is encoded by the CTBP1 gene.[1]

Function

The CtBP1 protein was originally identified as a human protein that bound a PLDLS motif in the C-terminus of adenovirus E1A proteins. It and the related protein CTBP2 were later shown to function as transcriptional corepressors.[2] That is, regulatory proteins that bind to sequence-specific DNA-binding proteins and help turn genes off. CtBPs do this by recruiting histone modifying enzymes that add repressive histone marks and remove activating marks. CtBP proteins can also self-associate and presumably bring together gene regulatory complexes.[3]

CtBP1 is broadly expressed from embryo to adult, while CtBP2 has a somewhat more restricted pattern of expression. CtBPs have multiple biological roles and appear to be most important in regulating the epithelial to mesenchymal transition, as well as influencing metabolism. They do the latter by binding NADH in preference to NAD+, thereby sensing the NADH/NAD+ ratio. When bound it undergoes a conformational change that allows it to dimerize and associate with its partner proteins and silence specific genes.

During skeletal and T cell development, CtBP1 and CtBP2 associate with the PLDLSL domain of δEF1, a cellular zinc finger-homeodomain protein, and thereby enhances δEF1-induced transcriptional silencing. CtBP also binds the Kruppel-like factors family of zinc finger proteins KLF3, KLF8 and KLF12. In addition, CtBP complexes with CtIP, a 125 kDa protein that recognizes distinctly different protein motifs from CtBP. CtIP binds to the BRCT repeats within the breast cancer gene BRCA1 and enables CtBP to influence BRCA1 activity. Both proteins can also interact with a polycomb group protein complex which participates in regulation of gene expression during development. Alternative splicing of transcripts from this gene results in multiple transcript variants.[4]

Interactions

CTBP1 has been shown to interact with:

References

  1. ↑ 1.0 1.1 Schaeper U, Subramanian T, Lim L, Boyd JM, Chinnadurai G (April 1998). "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". J. Biol. Chem. 273 (15): 8549–52. doi:10.1074/jbc.273.15.8549. PMID 9535825.
  2. ↑ 2.0 2.1 Turner J, Crossley M (September 1998). "Cloning and characterization of mCtBP2, a co-repressor that associates with basic Krüppel-like factor and other mammalian transcriptional regulators". EMBO J. 17 (17): 5129–40. doi:10.1093/emboj/17.17.5129. PMC 1170841. PMID 9724649.
  3. ↑ Chinnadurai G (2002). "CtBP, an unconventional transcriptional corepressor in development and oncogenesis". Mol. Cell. 9 (2): 213–24. doi:10.1016/S1097-2765(02)00443-4. PMID 11864595.
  4. ↑ "Entrez Gene: CTBP1 C-terminal binding protein 1".
  5. ↑ Oma Y, Nishimori K, Harata M (February 2003). "The brain-specific actin-related protein ArpN alpha interacts with the transcriptional co-repressor CtBP". Biochem. Biophys. Res. Commun. 301 (2): 521–8. doi:10.1016/S0006-291X(02)03073-5. PMID 12565893.
  6. ↑ Paliwal S, Pande S, Kovi RC, Sharpless NE, Bardeesy N, Grossman SR (March 2006). "Targeting of C-Terminal Binding Protein (CtBP) by ARF Results in p53-Independent Apoptosis". Mol. Cell. Biol. 26 (6): 2360–72. doi:10.1128/MCB.26.6.2360-2372.2006. PMC 1430274. PMID 16508011.
  7. ↑ Chakraborty S, Senyuk V, Sitailo S, Chi Y, Nucifora G (November 2001). "Interaction of EVI1 with cAMP-responsive element-binding protein-binding protein (CBP) and p300/CBP-associated factor (P/CAF) results in reversible acetylation of EVI1 and in co-localization in nuclear speckles". J. Biol. Chem. 276 (48): 44936–43. doi:10.1074/jbc.M106733200. PMID 11568182.
  8. ↑ Izutsu K, Kurokawa M, Imai Y, Maki K, Mitani K, Hirai H (May 2001). "The corepressor CtBP interacts with Evi-1 to repress transforming growth factor beta signaling". Blood. 97 (9): 2815–22. doi:10.1182/blood.V97.9.2815. PMID 11313276.
  9. ↑ Li S, Weidenfeld J, Morrisey EE (January 2004). "Transcriptional and DNA Binding Activity of the Foxp1/2/4 Family Is Modulated by Heterotypic and Homotypic Protein Interactions". Mol. Cell. Biol. 24 (2): 809–22. doi:10.1128/MCB.24.2.809-822.2004. PMC 343786. PMID 14701752.
  10. ↑ Zhang CL, McKinsey TA, Lu JR, Olson EN (January 2001). "Association of COOH-terminal-binding protein (CtBP) and MEF2-interacting transcription repressor (MITR) contributes to transcriptional repression of the MEF2 transcription factor". J. Biol. Chem. 276 (1): 35–9. doi:10.1074/jbc.M007364200. PMID 11022042.
  11. ↑ 11.0 11.1 Melhuish TA, Wotton D (December 2000). "The interaction of the carboxyl terminus-binding protein with the Smad corepressor TGIF is disrupted by a holoprosencephaly mutation in TGIF". J. Biol. Chem. 275 (50): 39762–6. doi:10.1074/jbc.C000416200. PMID 10995736.
  12. ↑ Sundqvist A, Sollerbrant K, Svensson C (June 1998). "The carboxy-terminal region of adenovirus E1A activates transcription through targeting of a C-terminal binding protein-histone deacetylase complex". FEBS Lett. 429 (2): 183–8. doi:10.1016/S0014-5793(98)00588-2. PMID 9650586.
  13. ↑ Koipally J, Georgopoulos K (June 2000). "Ikaros interactions with CtBP reveal a repression mechanism that is independent of histone deacetylase activity". J. Biol. Chem. 275 (26): 19594–602. doi:10.1074/jbc.M000254200. PMID 10766745.
  14. ↑ Perdomo J, Crossley M (December 2002). "The Ikaros family protein Eos associates with C-terminal-binding protein corepressors". Eur. J. Biochem. 269 (23): 5885–92. doi:10.1046/j.1432-1033.2002.03313.x. PMID 12444977.
  15. ↑ van Vliet J, Turner J, Crossley M (May 2000). "Human Krüppel-like factor 8: a CACCC-box binding protein that associates with CtBP and represses transcription". Nucleic Acids Res. 28 (9): 1955–62. doi:10.1093/nar/28.9.1955. PMC 103308. PMID 10756197.
  16. ↑ Mirnezami AH, Campbell SJ, Darley M, Primrose JN, Johnson PW, Blaydes JP (July 2003). "Hdm2 recruits a hypoxia-sensitive corepressor to negatively regulate p53-dependent transcription". Curr. Biol. 13 (14): 1234–9. doi:10.1016/S0960-9822(03)00454-8. PMID 12867035.
  17. ↑ Xia ZB, Anderson M, Diaz MO, Zeleznik-Le NJ (July 2003). "MLL repression domain interacts with histone deacetylases, the polycomb group proteins HPC2 and BMI-1, and the corepressor C-terminal-binding protein". Proc. Natl. Acad. Sci. U.S.A. 100 (14): 8342–7. doi:10.1073/pnas.1436338100. PMC 166231. PMID 12829790.
  18. ↑ Castet A, Boulahtouf A, Versini G, Bonnet S, Augereau P, Vignon F, Khochbin S, Jalaguier S, Cavaillès V (2004). "Multiple domains of the Receptor-Interacting Protein 140 contribute to transcription inhibition". Nucleic Acids Res. 32 (6): 1957–66. doi:10.1093/nar/gkh524. PMC 390375. PMID 15060175.
  19. ↑ Perissi V, Scafoglio C, Zhang J, Ohgi KA, Rose DW, Glass CK, Rosenfeld MG (March 2008). "TBL1 and TBLR1 Phosphorylation on Regulated Gene Promoters Overcomes Dual CtBP and NCoR/SMRT Transcriptional Repression Checkpoints". Mol. Cell. 29 (6): 755–66. doi:10.1016/j.molcel.2008.01.020. PMC 2364611. PMID 18374649.
  20. ↑ Alpatov R, Munguba GC, Caton P, Joo JH, Shi Y, Shi Y, Hunt ME, Sugrue SP (December 2004). "Nuclear Speckle-Associated Protein Pnn/DRS Binds to the Transcriptional Corepressor CtBP and Relieves CtBP- Mediated Repression of the E-Cadherin Gene". Mol. Cell. Biol. 24 (23): 10223–35. doi:10.1128/MCB.24.23.10223-10235.2004. PMC 529029. PMID 15542832.
  21. ↑ Li S, Chen PL, Subramanian T, Chinnadurai G, Tomlinson G, Osborne CK, Sharp ZD, Lee WH (April 1999). "Binding of CtIP to the BRCT repeats of BRCA1 involved in the transcription regulation of p21 is disrupted upon DNA damage". J. Biol. Chem. 274 (16): 11334–8. doi:10.1074/jbc.274.16.11334. PMID 10196224.

Further reading

External links

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