CTBP1: Difference between revisions

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{{Infobox_gene}}
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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]].<ref name="pmid9535825">{{cite journal |vauthors=Schaeper U, Subramanian T, Lim L, Boyd JM, Chinnadurai G | title = 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 | journal = J. Biol. Chem. | volume = 273 | issue = 15 | pages = 8549–52 |date=April 1998 | pmid = 9535825 | doi = 10.1074/jbc.273.15.8549 }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}
<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{GNF_Protein_box
| image = PBB_Protein_CTBP1_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1hku.
| PDB = {{PDB2|1hku}}, {{PDB2|1hl3}}, {{PDB2|1mx3}}, {{PDB2|2hu2}}
| Name = C-terminal binding protein 1
| HGNCid = 2494
| Symbol = CTBP1
| AltSymbols =; BARS; MGC104684
| OMIM = 602618
| ECnumber =
| Homologene = 1015
| MGIid = 1201685
| GeneAtlas_image1 = PBB_GE_CTBP1_203392_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_CTBP1_212863_x_at_tn.png
| GeneAtlas_image3 = PBB_GE_CTBP1_213980_s_at_tn.png
| Function = {{GNF_GO|id=GO:0008022 |text = protein C-terminus binding}} {{GNF_GO|id=GO:0008134 |text = transcription factor binding}} {{GNF_GO|id=GO:0016491 |text = oxidoreductase activity}} {{GNF_GO|id=GO:0016616 |text = oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor}} {{GNF_GO|id=GO:0051287 |text = NAD binding}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}}
| Process = {{GNF_GO|id=GO:0006468 |text = protein amino acid phosphorylation}} {{GNF_GO|id=GO:0006564 |text = L-serine biosynthetic process}} {{GNF_GO|id=GO:0008152 |text = metabolic process}} {{GNF_GO|id=GO:0008285 |text = negative regulation of cell proliferation}} {{GNF_GO|id=GO:0019079 |text = viral genome replication}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 1487
    | Hs_Ensembl = ENSG00000159692
    | Hs_RefseqProtein = NP_001012632
    | Hs_RefseqmRNA = NM_001012614
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 4
    | Hs_GenLoc_start = 1195228
    | Hs_GenLoc_end = 1232925
    | Hs_Uniprot = Q13363
    | Mm_EntrezGene = 13016
    | Mm_Ensembl = ENSMUSG00000037373
    | Mm_RefseqmRNA = XM_990134
    | Mm_RefseqProtein = XP_995228
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 5
    | Mm_GenLoc_start = 33564581
    | Mm_GenLoc_end = 33591839
    | Mm_Uniprot = Q3TAT1
  }}
}}
'''C-terminal binding protein 1''', also known as '''CTBP1''', is a human [[gene]].


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
==Function==
{{PBB_Summary
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 [[corepressor]]s.<ref name="pmid9724649">{{cite journal |vauthors=Turner J, Crossley M | title = Cloning and characterization of mCtBP2, a co-repressor that associates with basic Krüppel-like factor and other mammalian transcriptional regulators | journal = EMBO J. | volume = 17 | issue = 17 | pages = 5129–40 |date=September 1998 | pmid = 9724649 | pmc = 1170841 | doi = 10.1093/emboj/17.17.5129 }}</ref> 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.<ref name=pmid11864595>{{cite journal  | author=Chinnadurai G |title=CtBP, an unconventional transcriptional corepressor in development and oncogenesis |journal=Mol. Cell |volume=9 |issue= 2 |pages= 213–24 |year= 2002 |pmid= 11864595 |doi=10.1016/S1097-2765(02)00443-4 }}</ref>
| section_title =  
 
| summary_text = This gene encodes a protein that binds to the C-terminus of adenovirus E1A proteins. This phosphoprotein is a transcriptional repressor and may play a role during cellular proliferation. This protein and the product of a second closely related gene, CTBP2, can dimerize. 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.<ref>{{cite web | title = Entrez Gene: CTBP1 C-terminal binding protein 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1487| accessdate = }}</ref>
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.<ref>{{cite web | title = Entrez Gene: CTBP1 C-terminal binding protein 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1487| accessdate = }}</ref>
 
==Interactions==
CTBP1 has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[ACTL6B]],<ref name="pmid12565893">{{cite journal |vauthors=Oma Y, Nishimori K, Harata M | title = The brain-specific actin-related protein ArpN alpha interacts with the transcriptional co-repressor CtBP | journal = Biochem. Biophys. Res. Commun. | volume = 301 | issue = 2 | pages = 521–8 |date=February 2003 | pmid = 12565893 | doi = 10.1016/S0006-291X(02)03073-5| url =  }}</ref>
* [[ADP ribosylation factor|ARF]],<ref name="pmid16508011">{{cite journal |vauthors=Paliwal S, Pande S, Kovi RC, Sharpless NE, Bardeesy N, Grossman SR | title = Targeting of C-Terminal Binding Protein (CtBP) by ARF Results in p53-Independent Apoptosis | journal = Mol. Cell. Biol. | volume = 26 | issue = 6 | pages = 2360–72 |date=March 2006 | pmid = 16508011 | pmc = 1430274 | doi = 10.1128/MCB.26.6.2360-2372.2006 | url =  }}</ref>
* [[EVI1]]<ref name="pmid11568182">{{cite journal |vauthors=Chakraborty S, Senyuk V, Sitailo S, Chi Y, Nucifora G | title = 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 | journal = J. Biol. Chem. | volume = 276 | issue = 48 | pages = 44936–43 |date=November 2001 | pmid = 11568182 | doi = 10.1074/jbc.M106733200 | url =  }}</ref><ref name="pmid11313276">{{cite journal |vauthors=Izutsu K, Kurokawa M, Imai Y, Maki K, Mitani K, Hirai H | title = The corepressor CtBP interacts with Evi-1 to repress transforming growth factor beta signaling | journal = Blood | volume = 97 | issue = 9 | pages = 2815–22 |date=May 2001 | pmid = 11313276 | doi = 10.1182/blood.V97.9.2815| url =  }}</ref>
* [[FOXP2]],<ref name="pmid14701752">{{cite journal |vauthors=Li S, Weidenfeld J, Morrisey EE | title = Transcriptional and DNA Binding Activity of the Foxp1/2/4 Family Is Modulated by Heterotypic and Homotypic Protein Interactions | journal = Mol. Cell. Biol. | volume = 24 | issue = 2 | pages = 809–22 |date=January 2004 | pmid = 14701752 | pmc = 343786 | doi = 10.1128/MCB.24.2.809-822.2004| url =  }}</ref>
* [[HDAC1]],<ref name="pmid11022042">{{cite journal |vauthors=Zhang CL, McKinsey TA, Lu JR, Olson EN | title = Association of COOH-terminal-binding protein (CtBP) and MEF2-interacting transcription repressor (MITR) contributes to transcriptional repression of the MEF2 transcription factor | journal = J. Biol. Chem. | volume = 276 | issue = 1 | pages = 35–9 |date=January 2001 | pmid = 11022042 | doi = 10.1074/jbc.M007364200 | url =  }}</ref><ref name="pmid10995736">{{cite journal |vauthors=Melhuish TA, Wotton D | title = The interaction of the carboxyl terminus-binding protein with the Smad corepressor TGIF is disrupted by a holoprosencephaly mutation in TGIF | journal = J. Biol. Chem. | volume = 275 | issue = 50 | pages = 39762–6 |date=December 2000 | pmid = 10995736 | doi = 10.1074/jbc.C000416200 | url =  }}</ref><ref name="pmid9650586">{{cite journal |vauthors=Sundqvist A, Sollerbrant K, Svensson C | title = The carboxy-terminal region of adenovirus E1A activates transcription through targeting of a C-terminal binding protein-histone deacetylase complex | journal = FEBS Lett. | volume = 429 | issue = 2 | pages = 183–8 |date=June 1998 | pmid = 9650586 | doi = 10.1016/S0014-5793(98)00588-2| url =  }}</ref>
* [[IKZF1]],<ref name="pmid10766745">{{cite journal |vauthors=Koipally J, Georgopoulos K | title = Ikaros interactions with CtBP reveal a repression mechanism that is independent of histone deacetylase activity | journal = J. Biol. Chem. | volume = 275 | issue = 26 | pages = 19594–602 |date=June 2000 | pmid = 10766745 | doi = 10.1074/jbc.M000254200 | url =  }}</ref>
* [[IKZF4]],<ref name="pmid12444977">{{cite journal |vauthors=Perdomo J, Crossley M | title = The Ikaros family protein Eos associates with C-terminal-binding protein corepressors | journal = Eur. J. Biochem. | volume = 269 | issue = 23 | pages = 5885–92 |date=December 2002 | pmid = 12444977 | doi = 10.1046/j.1432-1033.2002.03313.x| url =  }}</ref>
* [[KLF3]],<ref name="pmid9724649"/>
* [[KLF8]],<ref name="pmid10756197">{{cite journal |vauthors=van Vliet J, Turner J, Crossley M | title = Human Krüppel-like factor 8: a CACCC-box binding protein that associates with CtBP and represses transcription | journal = Nucleic Acids Res. | volume = 28 | issue = 9 | pages = 1955–62 |date=May 2000 | pmid = 10756197 | pmc = 103308 | doi = 10.1093/nar/28.9.1955}}</ref>
* [[Mdm2]],<ref name="pmid12867035">{{cite journal |vauthors=Mirnezami AH, Campbell SJ, Darley M, Primrose JN, Johnson PW, Blaydes JP | title = Hdm2 recruits a hypoxia-sensitive corepressor to negatively regulate p53-dependent transcription | journal = Curr. Biol. | volume = 13 | issue = 14 | pages = 1234–9 |date=July 2003 | pmid = 12867035 | doi = 10.1016/S0960-9822(03)00454-8| url =  }}</ref>
* [[MLL (gene)|MLL]],<ref name="pmid12829790">{{cite journal |vauthors=Xia ZB, Anderson M, Diaz MO, Zeleznik-Le NJ | title = MLL repression domain interacts with histone deacetylases, the polycomb group proteins HPC2 and BMI-1, and the corepressor C-terminal-binding protein | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 100 | issue = 14 | pages = 8342–7 |date=July 2003 | pmid = 12829790 | pmc = 166231 | doi = 10.1073/pnas.1436338100 | url =  }}</ref>
* [[NRIP1]],<ref name="pmid15060175">{{cite journal |vauthors=Castet A, Boulahtouf A, Versini G, Bonnet S, Augereau P, Vignon F, Khochbin S, Jalaguier S, Cavaillès V | title = Multiple domains of the Receptor-Interacting Protein 140 contribute to transcription inhibition | journal = Nucleic Acids Res. | volume = 32 | issue = 6 | pages = 1957–66 | year = 2004 | pmid = 15060175 | pmc = 390375 | doi = 10.1093/nar/gkh524 | url =  }}</ref><ref name="pmid18374649">{{cite journal |vauthors=Perissi V, Scafoglio C, Zhang J, Ohgi KA, Rose DW, Glass CK, Rosenfeld MG | title = TBL1 and TBLR1 Phosphorylation on Regulated Gene Promoters Overcomes Dual CtBP and NCoR/SMRT Transcriptional Repression Checkpoints | journal = Mol. Cell | volume = 29 | issue = 6 | pages = 755–66 |date=March 2008 | pmid = 18374649 | pmc = 2364611 | doi = 10.1016/j.molcel.2008.01.020 | url =  }}</ref>
* [[Pinin]],<ref name="pmid15542832">{{cite journal |vauthors=Alpatov R, Munguba GC, Caton P, Joo JH, Shi Y, Shi Y, Hunt ME, Sugrue SP | title = Nuclear Speckle-Associated Protein Pnn/DRS Binds to the Transcriptional Corepressor CtBP and Relieves CtBP- Mediated Repression of the E-Cadherin Gene | journal = Mol. Cell. Biol. | volume = 24 | issue = 23 | pages = 10223–35 |date=December 2004 | pmid = 15542832 | pmc = 529029 | doi = 10.1128/MCB.24.23.10223-10235.2004 | url =  }}</ref>
* [[RBBP8]],<ref name="pmid9535825" /><ref name="pmid10196224">{{cite journal |vauthors=Li S, Chen PL, Subramanian T, Chinnadurai G, Tomlinson G, Osborne CK, Sharp ZD, Lee WH | title = Binding of CtIP to the BRCT repeats of BRCA1 involved in the transcription regulation of p21 is disrupted upon DNA damage | journal = J. Biol. Chem. | volume = 274 | issue = 16 | pages = 11334–8 |date=April 1999 | pmid = 10196224 | doi = 10.1074/jbc.274.16.11334| url =  }}</ref> and
* [[Homeobox protein TGIF1|TGIF1]].<ref name="pmid10995736"/>
{{Div col end}}


==References==
==References==
{{reflist|2}}
{{reflist}}
 
==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin|35em}}
{{PBB_Further_reading
*{{cite journal  | author=Chinnadurai G |title=CtBP, an unconventional transcriptional corepressor in development and oncogenesis |journal=Mol. Cell |volume=9 |issue= 2 |pages= 213–24 |year= 2002 |pmid= 11864595 |doi=10.1016/S1097-2765(02)00443-4 }}
| citations =
*{{cite journal  | author=Schaeper U |title=Molecular cloning and characterization of a cellular phosphoprotein that interacts with a conserved C-terminal domain of adenovirus E1A involved in negative modulation of oncogenic transformation |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=92 |issue= 23 |pages= 10467–71 |year= 1995 |pmid= 7479821 |doi=10.1073/pnas.92.23.10467 | pmc=40632 |name-list-format=vanc| author2=Boyd JM | author3=Verma S  | display-authors=3  | last4=Uhlmann  | first4=E  | last5=Subramanian  | first5=T  | last6=Chinnadurai  | first6=G  }}
*{{cite journal  | author=Chinnadurai G |title=CtBP, an unconventional transcriptional corepressor in development and oncogenesis. |journal=Mol. Cell |volume=9 |issue= 2 |pages= 213-24 |year= 2002 |pmid= 11864595 |doi=  }}
*{{cite journal  | author=Boyd JM |title=A region in the C-terminus of adenovirus 2/5 E1a protein is required for association with a cellular phosphoprotein and important for the negative modulation of T24-ras mediated transformation, tumorigenesis and metastasis |journal=EMBO J. |volume=12 |issue= 2 |pages= 469–78 |year= 1993 |pmid= 8440238 |doi=  | pmc=413230  |name-list-format=vanc| author2=Subramanian T | author3=Schaeper U  | display-authors=3  | last4=La Regina  | first4=M  | last5=Bayley  | first5=S  | last6=Chinnadurai  | first6=G  }}
*{{cite journal  | author=Schaeper U, Boyd JM, Verma S, ''et al.'' |title=Molecular cloning and characterization of a cellular phosphoprotein that interacts with a conserved C-terminal domain of adenovirus E1A involved in negative modulation of oncogenic transformation. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=92 |issue= 23 |pages= 10467-71 |year= 1995 |pmid= 7479821 |doi=  }}
*{{cite journal  | author=Schaeper U |title=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 |journal=J. Biol. Chem. |volume=273 |issue= 15 |pages= 8549–52 |year= 1998 |pmid= 9535825 |doi=10.1074/jbc.273.15.8549 |name-list-format=vanc| author2=Subramanian T | author3=Lim L  | display-authors=3  | last4=Boyd  | first4=JM  | last5=Chinnadurai  | first5=G  }}
*{{cite journal | author=Boyd JM, Subramanian T, Schaeper U, ''et al.'' |title=A region in the C-terminus of adenovirus 2/5 E1a protein is required for association with a cellular phosphoprotein and important for the negative modulation of T24-ras mediated transformation, tumorigenesis and metastasis. |journal=EMBO J. |volume=12 |issue= 2 |pages= 469-78 |year= 1993 |pmid= 8440238 |doi=  }}
*{{cite journal  |vauthors=Sundqvist A, Sollerbrant K, Svensson C |title=The carboxy-terminal region of adenovirus E1A activates transcription through targeting of a C-terminal binding protein-histone deacetylase complex |journal=FEBS Lett. |volume=429 |issue= 2 |pages= 183–8 |year= 1998 |pmid= 9650586 |doi=10.1016/S0014-5793(98)00588-2 }}
*{{cite journal  | author=Katsanis N, Fisher EM |title=A novel C-terminal binding protein (CTBP2) is closely related to CTBP1, an adenovirus E1A-binding protein, and maps to human chromosome 21q21.3. |journal=Genomics |volume=47 |issue= 2 |pages= 294-9 |year= 1998 |pmid= 9479502 |doi= 10.1006/geno.1997.5115 }}
*{{cite journal  |vauthors=Fuks F, Milner J, Kouzarides T |title=BRCA2 associates with acetyltransferase activity when bound to P/CAF |journal=Oncogene |volume=17 |issue= 19 |pages= 2531–4 |year= 1998 |pmid= 9824164 |doi= 10.1038/sj.onc.1202475 }}
*{{cite journal | author=Schaeper U, Subramanian T, Lim L, ''et al.'' |title=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. |journal=J. Biol. Chem. |volume=273 |issue= 15 |pages= 8549-52 |year= 1998 |pmid= 9535825 |doi=  }}
*{{cite journal  | author=Sewalt RG |title=C-Terminal Binding Protein Is a Transcriptional Repressor That Interacts with a Specific Class of Vertebrate Polycomb Proteins |journal=Mol. Cell. Biol. |volume=19 |issue= 1 |pages= 777–87 |year= 1999 |pmid= 9858600 |doi=  | pmc=83934 |name-list-format=vanc| author2=Gunster MJ  | author3=van der Vlag J  | display-authors=3  | last4=Satijn  | first4=DP  | last5=Otte  | first5=AP  }}
*{{cite journal  | author=Sundqvist A, Sollerbrant K, Svensson C |title=The carboxy-terminal region of adenovirus E1A activates transcription through targeting of a C-terminal binding protein-histone deacetylase complex. |journal=FEBS Lett. |volume=429 |issue= 2 |pages= 183-8 |year= 1998 |pmid= 9650586 |doi=  }}
*{{cite journal  | author=Li S |title=Binding of CtIP to the BRCT repeats of BRCA1 involved in the transcription regulation of p21 is disrupted upon DNA damage |journal=J. Biol. Chem. |volume=274 |issue= 16 |pages= 11334–8 |year= 1999 |pmid= 10196224 |doi=10.1074/jbc.274.16.11334  |name-list-format=vanc| author2=Chen PL  | author3=Subramanian T  | display-authors=3  | last4=Chinnadurai  | first4=G  | last5=Tomlinson  | first5=G | last6=Osborne | first6=CK  | last7=Sharp  | first7=ZD  | last8=Lee  | first8=WH }}
*{{cite journal | author=Fuks F, Milner J, Kouzarides T |title=BRCA2 associates with acetyltransferase activity when bound to P/CAF. |journal=Oncogene |volume=17 |issue= 19 |pages= 2531-4 |year= 1998 |pmid= 9824164 |doi= 10.1038/sj.onc.1202475 }}
*{{cite journal  |vauthors=Postigo AA, Dean DC |title=ZEB represses transcription through interaction with the corepressor CtBP |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=96 |issue= 12 |pages= 6683–8 |year= 1999 |pmid= 10359772 |doi=10.1073/pnas.96.12.6683  | pmc=21975  }}
*{{cite journal  | author=Sewalt RG, Gunster MJ, van der Vlag J, ''et al.'' |title=C-Terminal binding protein is a transcriptional repressor that interacts with a specific class of vertebrate Polycomb proteins. |journal=Mol. Cell. Biol. |volume=19 |issue= 1 |pages= 777-87 |year= 1999 |pmid= 9858600 |doi=  }}
*{{cite journal  |vauthors=Criqui-Filipe P, Ducret C, Maira SM, Wasylyk B |title=Net, a negative Ras-switchable TCF, contains a second inhibition domain, the CID, that mediates repression through interactions with CtBP and de-acetylation |journal=EMBO J. |volume=18 |issue= 12 |pages= 3392–403 |year= 1999 |pmid= 10369679 |doi= 10.1093/emboj/18.12.3392  | pmc=1171419 }}
*{{cite journal  | author=Li S, Chen PL, Subramanian T, ''et al.'' |title=Binding of CtIP to the BRCT repeats of BRCA1 involved in the transcription regulation of p21 is disrupted upon DNA damage. |journal=J. Biol. Chem. |volume=274 |issue= 16 |pages= 11334-8 |year= 1999 |pmid= 10196224 |doi= }}
*{{cite journal  | author=Holmes M |title=hFOG-2, a novel zinc finger protein, binds the co-repressor mCtBP2 and modulates GATA-mediated activation |journal=J. Biol. Chem. |volume=274 |issue= 33 |pages= 23491–8 |year= 1999 |pmid= 10438528 |doi=10.1074/jbc.274.33.23491 |name-list-format=vanc| author2=Turner J  | author3=Fox A  | display-authors=3  | last4=Chisholm  | first4=O  | last5=Crossley  | first5=M  | last6=Chong  | first6=B  }}
*{{cite journal  | author=Postigo AA, Dean DC |title=ZEB represses transcription through interaction with the corepressor CtBP. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=96 |issue= 12 |pages= 6683-8 |year= 1999 |pmid= 10359772 |doi=  }}
*{{cite journal  |vauthors=Furusawa T, Moribe H, Kondoh H, Higashi Y |title=Identification of CtBP1 and CtBP2 as Corepressors of Zinc Finger-Homeodomain Factor δEF1 |journal=Mol. Cell. Biol. |volume=19 |issue= 12 |pages= 8581–90 |year= 2000 |pmid= 10567582 |doi= 10.1128/mcb.19.12.8581| pmc=84984 }}
*{{cite journal | author=Criqui-Filipe P, Ducret C, Maira SM, Wasylyk B |title=Net, a negative Ras-switchable TCF, contains a second inhibition domain, the CID, that mediates repression through interactions with CtBP and de-acetylation. |journal=EMBO J. |volume=18 |issue= 12 |pages= 3392-403 |year= 1999 |pmid= 10369679 |doi= 10.1093/emboj/18.12.3392 }}
*{{cite journal  |vauthors=Yu X, Baer R |title=Nuclear localization and cell cycle-specific expression of CtIP, a protein that associates with the BRCA1 tumor suppressor |journal=J. Biol. Chem. |volume=275 |issue= 24 |pages= 18541–9 |year= 2000 |pmid= 10764811 |doi= 10.1074/jbc.M909494199 }}
*{{cite journal  | author=Holmes M, Turner J, Fox A, ''et al.'' |title=hFOG-2, a novel zinc finger protein, binds the co-repressor mCtBP2 and modulates GATA-mediated activation. |journal=J. Biol. Chem. |volume=274 |issue= 33 |pages= 23491-8 |year= 1999 |pmid= 10438528 |doi=  }}
*{{cite journal  |vauthors=Koipally J, Georgopoulos K |title=Ikaros interactions with CtBP reveal a repression mechanism that is independent of histone deacetylase activity |journal=J. Biol. Chem. |volume=275 |issue= 26 |pages= 19594–602 |year= 2000 |pmid= 10766745 |doi= 10.1074/jbc.M000254200 }}
*{{cite journal | author=Furusawa T, Moribe H, Kondoh H, Higashi Y |title=Identification of CtBP1 and CtBP2 as corepressors of zinc finger-homeodomain factor deltaEF1. |journal=Mol. Cell. Biol. |volume=19 |issue= 12 |pages= 8581-90 |year= 2000 |pmid= 10567582 |doi=  }}
*{{cite journal  |vauthors=Melhuish TA, Wotton D |title=The interaction of the carboxyl terminus-binding protein with the Smad corepressor TGIF is disrupted by a holoprosencephaly mutation in TGIF |journal=J. Biol. Chem. |volume=275 |issue= 50 |pages= 39762–6 |year= 2001 |pmid= 10995736 |doi= 10.1074/jbc.C000416200 }}
*{{cite journal  | author=Yu X, Baer R |title=Nuclear localization and cell cycle-specific expression of CtIP, a protein that associates with the BRCA1 tumor suppressor. |journal=J. Biol. Chem. |volume=275 |issue= 24 |pages= 18541-9 |year= 2000 |pmid= 10764811 |doi= 10.1074/jbc.M909494199 }}
*{{cite journal  |vauthors=Zhang CL, McKinsey TA, Lu JR, Olson EN |title=Association of COOH-terminal-binding protein (CtBP) and MEF2-interacting transcription repressor (MITR) contributes to transcriptional repression of the MEF2 transcription factor |journal=J. Biol. Chem. |volume=276 |issue= 1 |pages= 35–9 |year= 2001 |pmid= 11022042 |doi= 10.1074/jbc.M007364200 }}
*{{cite journal  | author=Koipally J, Georgopoulos K |title=Ikaros interactions with CtBP reveal a repression mechanism that is independent of histone deacetylase activity. |journal=J. Biol. Chem. |volume=275 |issue= 26 |pages= 19594-602 |year= 2000 |pmid= 10766745 |doi= 10.1074/jbc.M000254200 }}
*{{cite journal  | author=Izutsu K |title=The corepressor CtBP interacts with Evi-1 to repress transforming growth factor beta signaling |journal=Blood |volume=97 |issue= 9 |pages= 2815–22 |year= 2001 |pmid= 11313276 |doi=10.1182/blood.V97.9.2815  |name-list-format=vanc| author2=Kurokawa M  | author3=Imai Y  | display-authors=3  | last4=Maki  | first4=K  | last5=Mitani  | first5=K  | last6=Hirai  | first6=H  }}
*{{cite journal  | author=Melhuish TA, Wotton D |title=The interaction of the carboxyl terminus-binding protein with the Smad corepressor TGIF is disrupted by a holoprosencephaly mutation in TGIF. |journal=J. Biol. Chem. |volume=275 |issue= 50 |pages= 39762-6 |year= 2001 |pmid= 10995736 |doi= 10.1074/jbc.C000416200 }}
*{{cite journal  | author=Palmer S |title=Evi-1 transforming and repressor activities are mediated by CtBP co-repressor proteins |journal=J. Biol. Chem. |volume=276 |issue= 28 |pages= 25834–40 |year= 2001 |pmid= 11328817 |doi= 10.1074/jbc.M102343200  |name-list-format=vanc| author2=Brouillet JP  | author3=Kilbey A  | display-authors=3  | last4=Fulton  | first4=R  | last5=Walker  | first5=M  | last6=Crossley  | first6=M  | last7=Bartholomew  | first7=C }}
*{{cite journal | author=Zhang CL, McKinsey TA, Lu JR, Olson EN |title=Association of COOH-terminal-binding protein (CtBP) and MEF2-interacting transcription repressor (MITR) contributes to transcriptional repression of the MEF2 transcription factor. |journal=J. Biol. Chem. |volume=276 |issue= 1 |pages= 35-9 |year= 2001 |pmid= 11022042 |doi= 10.1074/jbc.M007364200 }}
*{{cite journal  | author=Schuierer M |title=Induction of AP-2alpha expression by adenoviral infection involves inactivation of the AP-2rep transcriptional corepressor CtBP1 |journal=J. Biol. Chem. |volume=276 |issue= 30 |pages= 27944–9 |year= 2001 |pmid= 11373277 |doi= 10.1074/jbc.M100070200  |name-list-format=vanc| author2=Hilger-Eversheim K  | author3=Dobner T  | display-authors=3  | last4=Bosserhoff  | first4=AK  | last5=Moser  | first5=M  | last6=Turner  | first6=J  | last7=Crossley  | first7=M  | last8=Buettner  | first8=R }}
*{{cite journal  | author=Izutsu K, Kurokawa M, Imai Y, ''et al.'' |title=The corepressor CtBP interacts with Evi-1 to repress transforming growth factor beta signaling. |journal=Blood |volume=97 |issue= 9 |pages= 2815-22 |year= 2001 |pmid= 11313276 |doi=  }}
*{{cite journal  | author=Palmer S, Brouillet JP, Kilbey A, ''et al.'' |title=Evi-1 transforming and repressor activities are mediated by CtBP co-repressor proteins. |journal=J. Biol. Chem. |volume=276 |issue= 28 |pages= 25834-40 |year= 2001 |pmid= 11328817 |doi= 10.1074/jbc.M102343200 }}
*{{cite journal  | author=Schuierer M, Hilger-Eversheim K, Dobner T, ''et al.'' |title=Induction of AP-2alpha expression by adenoviral infection involves inactivation of the AP-2rep transcriptional corepressor CtBP1. |journal=J. Biol. Chem. |volume=276 |issue= 30 |pages= 27944-9 |year= 2001 |pmid= 11373277 |doi= 10.1074/jbc.M100070200 }}
}}
{{refend}}
{{refend}}


{{protein-stub}}
==External links==
{{WikiDoc Sources}}
* {{UCSC gene info|CTBP1}}
{{PDB Gallery|geneid=1487}}
{{Transcription coregulators}}
 
[[Category:Transcription coregulators]]

Revision as of 10:09, 30 August 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
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View/Edit Human

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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