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Transcription co-repressor
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PDB id
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1hku
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Contents |
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* Residue conservation analysis
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PDB id:
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| Name: |
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Transcription co-repressor
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Title:
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Ctbp/bars: a dual-function protein involved in transcription corepression and golgi membrane fission
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Structure:
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C-terminal binding protein 3. Chain: a. Fragment: residues 1-350. Synonym: ctbp3. Engineered: yes
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Source:
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Rattus norvegicus. Rat. Organism_taxid: 10116. Organ: brain. Expressed in: escherichia coli. Expression_system_taxid: 469008.
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Biol. unit:
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Dimer (from PDB file)
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Resolution:
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2.30Å
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R-factor:
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0.222
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R-free:
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0.281
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Authors:
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M.Nardini,S.Spano',C.Cericola,A.Pesce,A.Massaro,E.Millo, A.Luini,D.Corda,M.Bolognesi
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Key ref:
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M.Nardini
et al.
(2003).
CtBP/BARS: a dual-function protein involved in transcription co-repression and Golgi membrane fission.
Embo J,
22,
3122-3130.
PubMed id:
DOI:
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Date:
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11-Mar-03
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Release date:
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19-Jun-03
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PROCHECK
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Headers
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References
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Q9Z2F5
(CTBP1_RAT) -
C-terminal-binding protein 1
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Seq:
Struc:
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430 a.a.
332 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 1 residue position (black
cross)
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Gene Ontology (GO) functional annotation
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Biological process
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metabolic process
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2 terms
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Biochemical function
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nucleotide binding
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4 terms
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DOI no:
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Embo J
22:3122-3130
(2003)
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PubMed id:
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CtBP/BARS: a dual-function protein involved in transcription co-repression and Golgi membrane fission.
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M.Nardini,
S.Spanò,
C.Cericola,
A.Pesce,
A.Massaro,
E.Millo,
A.Luini,
D.Corda,
M.Bolognesi.
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ABSTRACT
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C-terminal-binding protein/brefeldin A-ADP ribosylated substrate (CtBP/BARS)
plays key roles in development and oncogenesis as a transcription co-repressor,
and in intracellular traffic as a promoter of Golgi membrane fission.
Co-repressor activity is regulated by NAD(H) binding to CtBP/BARS, while
membrane fission is associated with its acyl-CoA-dependent acyltransferase
activity. Here, we report the crystal structures of rat CtBP/BARS in a binary
complex with NAD(H), and in a ternary complex with a PIDLSKK peptide mimicking
the consensus motif (PXDLS) recognized in CtBP/BARS cellular partners. The
structural data show CtBP/BARS in a NAD(H)-bound dimeric form; the peptide
binding maps the recognition site for DNA-binding proteins and histone
deacetylases to an N-terminal region of the protein. The crystal structure
together with the site-directed mutagenesis data and binding experiments suggest
a rationale for the molecular mechanisms underlying the two fundamental
co-existing, but diverse, activities supported by CtBP/BARS in the nucleus and
in Golgi membranes.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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C.N.Birts,
L.M.Bergman,
and
J.P.Blaydes
(2011).
CtBPs promote mitotic fidelity through their activities in the cell nucleus.
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| |
Oncogene, 30,
1272-1280.
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|
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C.N.Birts,
R.Harding,
G.Soosaipillai,
T.Halder,
A.Azim-Araghi,
M.Darley,
R.I.Cutress,
A.C.Bateman,
and
J.P.Blaydes
(2010).
Expression of CtBP family protein isoforms in breast cancer and their role in chemoresistance.
|
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Biol Cell, 103,
1.
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D.L.Madison,
and
J.R.Lundblad
(2010).
C-terminal binding protein and poly(ADP)ribose polymerase 1 contribute to repression of the p21(waf1/cip1) promoter.
|
| |
Oncogene, 29,
6027-6039.
|
|
|
|
|
|
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K.J.McLaughlin,
C.M.Strain-Damerell,
K.Xie,
D.Brekasis,
A.S.Soares,
M.S.Paget,
and
C.L.Kielkopf
(2010).
Structural basis for NADH/NAD+ redox sensing by a Rex family repressor.
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| |
Mol Cell, 38,
563-575.
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PDB codes:
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L.Z.Zhao,
and
G.Chinnadurai
(2010).
Incapacitating CtBP to kill cancer.
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Cell Cycle, 9,
3645-3646.
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|
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M.G.Roukens,
M.Alloul-Ramdhani,
B.Baan,
K.Kobayashi,
J.Peterson-Maduro,
H.van Dam,
S.Schulte-Merker,
and
D.A.Baker
(2010).
Control of endothelial sprouting by a Tel-CtBP complex.
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Nat Cell Biol, 12,
933-942.
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J.H.Wei,
and
J.Seemann
(2009).
Mitotic division of the mammalian Golgi apparatus.
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Semin Cell Dev Biol, 20,
810-816.
|
|
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L.J.Zhao,
M.Kuppuswamy,
S.Vijayalingam,
and
G.Chinnadurai
(2009).
Interaction of ZEB and histone deacetylase with the PLDLS-binding cleft region of monomeric C-terminal binding protein 2.
|
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BMC Mol Biol, 10,
89.
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L.M.Bergman,
C.N.Birts,
M.Darley,
B.Gabrielli,
and
J.P.Blaydes
(2009).
CtBPs promote cell survival through the maintenance of mitotic fidelity.
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| |
Mol Cell Biol, 29,
4539-4551.
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|
|
|
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F.R.Salsbury,
S.T.Knutson,
L.B.Poole,
and
J.S.Fetrow
(2008).
Functional site profiling and electrostatic analysis of cysteines modifiable to cysteine sulfenic acid.
|
| |
Protein Sci, 17,
299-312.
|
|
|
|
|
|
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K.Alpadi,
V.G.Magupalli,
S.Käppel,
L.Köblitz,
K.Schwarz,
G.M.Seigel,
C.H.Sung,
and
F.Schmitz
(2008).
RIBEYE recruits Munc119, a mammalian ortholog of the Caenorhabditis elegans protein unc119, to synaptic ribbons of photoreceptor synapses.
|
| |
J Biol Chem, 283,
26461-26467.
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|
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M.Jose,
D.K.Nair,
W.D.Altrock,
T.Dresbach,
E.D.Gundelfinger,
and
W.Zuschratter
(2008).
Investigating interactions mediated by the presynaptic protein bassoon in living cells by Foerster's resonance energy transfer and fluorescence lifetime imaging microscopy.
|
| |
Biophys J, 94,
1483-1496.
|
|
|
|
|
|
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M.Kuppuswamy,
S.Vijayalingam,
L.J.Zhao,
Y.Zhou,
T.Subramanian,
J.Ryerse,
and
G.Chinnadurai
(2008).
Role of the PLDLS-binding cleft region of CtBP1 in recruitment of core and auxiliary components of the corepressor complex.
|
| |
Mol Cell Biol, 28,
269-281.
|
|
|
|
|
|
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P.Liberali,
E.Kakkonen,
G.Turacchio,
C.Valente,
A.Spaar,
G.Perinetti,
R.A.Böckmann,
D.Corda,
A.Colanzi,
V.Marjomaki,
and
A.Luini
(2008).
The closure of Pak1-dependent macropinosomes requires the phosphorylation of CtBP1/BARS.
|
| |
EMBO J, 27,
970-981.
|
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|
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P.Pelka,
J.N.Ablack,
G.J.Fonseca,
A.F.Yousef,
and
J.S.Mymryk
(2008).
Intrinsic structural disorder in adenovirus E1A: a viral molecular hub linking multiple diverse processes.
|
| |
J Virol, 82,
7252-7263.
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|
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R.Alpatov,
Y.Shi,
G.C.Munguba,
B.Moghimi,
J.H.Joo,
J.Bungert,
and
S.P.Sugrue
(2008).
Corepressor CtBP and nuclear speckle protein Pnn/DRS differentially modulate transcription and splicing of the E-cadherin gene.
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| |
Mol Cell Biol, 28,
1584-1595.
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R.K.Bruton,
P.Pelka,
K.L.Mapp,
G.J.Fonseca,
J.Torchia,
A.S.Turnell,
J.S.Mymryk,
and
R.J.Grand
(2008).
Identification of a second CtBP binding site in adenovirus type 5 E1A conserved region 3.
|
| |
J Virol, 82,
8476-8486.
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|
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Y.Zhao,
J.Zhang,
H.Li,
Y.Li,
J.Ren,
M.Luo,
and
X.Zheng
(2008).
An NADPH sensor protein (HSCARG) down-regulates nitric oxide synthesis by association with argininosuccinate synthetase and is essential for epithelial cell viability.
|
| |
J Biol Chem, 283,
11004-11013.
|
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|
|
|
|
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A.Colanzi,
C.Hidalgo Carcedo,
A.Persico,
C.Cericola,
G.Turacchio,
M.Bonazzi,
A.Luini,
and
D.Corda
(2007).
The Golgi mitotic checkpoint is controlled by BARS-dependent fission of the Golgi ribbon into separate stacks in G2.
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EMBO J, 26,
2465-2476.
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G.Chinnadurai
(2007).
Transcriptional regulation by C-terminal binding proteins.
|
| |
Int J Biochem Cell Biol, 39,
1593-1607.
|
|
|
|
|
|
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L.J.Zhao,
T.Subramanian,
S.Vijayalingam,
and
G.Chinnadurai
(2007).
PLDLS-dependent interaction of E1A with CtBP: regulation of CtBP nuclear localization and transcriptional functions.
|
| |
Oncogene, 26,
7544-7551.
|
|
|
|
|
|
|
M.D.Stern,
H.Aihara,
K.H.Cho,
G.T.Kim,
G.Horiguchi,
G.A.Roccaro,
E.Guevara,
H.H.Sun,
D.Negeri,
H.Tsukaya,
and
Y.Nibu
(2007).
Structurally related Arabidopsis ANGUSTIFOLIA is functionally distinct from the transcriptional corepressor CtBP.
|
| |
Dev Genes Evol, 217,
759-769.
|
|
|
|
|
|
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P.Mani-Telang,
and
D.N.Arnosti
(2007).
Developmental expression and phylogenetic conservation of alternatively spliced forms of the C-terminal binding protein corepressor.
|
| |
Dev Genes Evol, 217,
127-135.
|
|
|
|
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|
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Q.Zhang,
S.Y.Wang,
C.Fleuriel,
D.Leprince,
J.V.Rocheleau,
D.W.Piston,
and
R.H.Goodman
(2007).
Metabolic regulation of SIRT1 transcription via a HIC1:CtBP corepressor complex.
|
| |
Proc Natl Acad Sci U S A, 104,
829-833.
|
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|
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R.Bartz,
J.Seemann,
J.K.Zehmer,
G.Serrero,
K.D.Chapman,
R.G.Anderson,
and
P.Liu
(2007).
Evidence that mono-ADP-ribosylation of CtBP1/BARS regulates lipid storage.
|
| |
Mol Biol Cell, 18,
3015-3025.
|
|
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|
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S.Vucetic,
H.Xie,
L.M.Iakoucheva,
C.J.Oldfield,
A.K.Dunker,
Z.Obradovic,
and
V.N.Uversky
(2007).
Functional anthology of intrinsic disorder. 2. Cellular components, domains, technical terms, developmental processes, and coding sequence diversities correlated with long disordered regions.
|
| |
J Proteome Res, 6,
1899-1916.
|
|
|
|
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|
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X.Li,
D.Kaloyanova,
M.van Eijk,
R.Eerland,
G.van der Goot,
V.Oorschot,
J.Klumperman,
F.Lottspeich,
V.Starkuviene,
F.T.Wieland,
and
J.B.Helms
(2007).
Involvement of a Golgi-resident GPI-anchored protein in maintenance of the Golgi structure.
|
| |
Mol Biol Cell, 18,
1261-1271.
|
|
|
|
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|
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X.Zheng,
X.Dai,
Y.Zhao,
Q.Chen,
F.Lu,
D.Yao,
Q.Yu,
X.Liu,
C.Zhang,
X.Gu,
and
M.Luo
(2007).
Restructuring of the dinucleotide-binding fold in an NADP(H) sensor protein.
|
| |
Proc Natl Acad Sci U S A, 104,
8809-8814.
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PDB code:
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|
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A.Verger,
K.G.Quinlan,
L.A.Crofts,
S.Spanò,
D.Corda,
E.P.Kable,
F.Braet,
and
M.Crossley
(2006).
Mechanisms directing the nuclear localization of the CtBP family proteins.
|
| |
Mol Cell Biol, 26,
4882-4894.
|
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|
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D.Corda,
A.Colanzi,
and
A.Luini
(2006).
The multiple activities of CtBP/BARS proteins: the Golgi view.
|
| |
Trends Cell Biol, 16,
167-173.
|
|
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|
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G.Egea,
F.Lázaro-Diéguez,
and
M.Vilella
(2006).
Actin dynamics at the Golgi complex in mammalian cells.
|
| |
Curr Opin Cell Biol, 18,
168-178.
|
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|
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H.Tsukaya
(2006).
Mechanism of leaf-shape determination.
|
| |
Annu Rev Plant Biol, 57,
477-496.
|
|
|
|
|
|
|
K.G.Quinlan,
A.Verger,
A.Kwok,
S.H.Lee,
J.Perdomo,
M.Nardini,
M.Bolognesi,
and
M.Crossley
(2006).
Role of the C-terminal binding protein PXDLS motif binding cleft in protein interactions and transcriptional repression.
|
| |
Mol Cell Biol, 26,
8202-8213.
|
|
|
|
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|
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K.G.Quinlan,
M.Nardini,
A.Verger,
P.Francescato,
P.Yaswen,
D.Corda,
M.Bolognesi,
and
M.Crossley
(2006).
Specific recognition of ZNF217 and other zinc finger proteins at a surface groove of C-terminal binding proteins.
|
| |
Mol Cell Biol, 26,
8159-8172.
|
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PDB code:
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|
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L.J.Zhao,
T.Subramanian,
and
G.Chinnadurai
(2006).
Changes in C-terminal binding protein 2 (CtBP2) corepressor complex induced by E1A and modulation of E1A transcriptional activity by CtBP2.
|
| |
J Biol Chem, 281,
36613-36623.
|
|
|
|
|
|
|
L.J.Zhao,
T.Subramanian,
Y.Zhou,
and
G.Chinnadurai
(2006).
Acetylation by p300 regulates nuclear localization and function of the transcriptional corepressor CtBP2.
|
| |
J Biol Chem, 281,
4183-4189.
|
|
|
|
|
|
|
L.M.Bergman,
and
J.P.Blaydes
(2006).
C-terminal binding proteins: emerging roles in cell survival and tumorigenesis.
|
| |
Apoptosis, 11,
879-888.
|
|
|
|
|
|
|
L.M.Bergman,
L.Morris,
M.Darley,
A.H.Mirnezami,
S.C.Gunatilake,
and
J.P.Blaydes
(2006).
Role of the unique N-terminal domain of CtBP2 in determining the subcellular localisation of CtBP family proteins.
|
| |
BMC Cell Biol, 7,
35.
|
|
|
|
|
|
|
M.Nardini,
D.Svergun,
P.V.Konarev,
S.Spanò,
M.Fasano,
C.Bracco,
A.Pesce,
A.Donadini,
C.Cericola,
F.Secundo,
A.Luini,
D.Corda,
and
M.Bolognesi
(2006).
The C-terminal domain of the transcriptional corepressor CtBP is intrinsically unstructured.
|
| |
Protein Sci, 15,
1042-1050.
|
|
|
|
|
|
|
N.Stankovic-Valentin,
A.Verger,
S.Deltour-Balerdi,
K.G.Quinlan,
M.Crossley,
and
D.Leprince
(2006).
A L225A substitution in the human tumour suppressor HIC1 abolishes its interaction with the corepressor CtBP.
|
| |
FEBS J, 273,
2879-2890.
|
|
|
|
|
|
|
Q.Zhang,
S.Y.Wang,
A.C.Nottke,
J.V.Rocheleau,
D.W.Piston,
and
R.H.Goodman
(2006).
Redox sensor CtBP mediates hypoxia-induced tumor cell migration.
|
| |
Proc Natl Acad Sci U S A, 103,
9029-9033.
|
|
|
|
|
|
|
E.A.Sickmier,
D.Brekasis,
S.Paranawithana,
J.B.Bonanno,
M.S.Paget,
S.K.Burley,
and
C.L.Kielkopf
(2005).
X-ray structure of a Rex-family repressor/NADH complex insights into the mechanism of redox sensing.
|
| |
Structure, 13,
43-54.
|
|
|
PDB code:
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|
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|
|
E.D.Prescott,
and
D.Zenisek
(2005).
Recent progress towards understanding the synaptic ribbon.
|
| |
Curr Opin Neurobiol, 15,
431-436.
|
|
|
|
|
|
|
J.L.Gallop,
P.J.Butler,
and
H.T.McMahon
(2005).
Endophilin and CtBP/BARS are not acyl transferases in endocytosis or Golgi fission.
|
| |
Nature, 438,
675-678.
|
|
|
|
|
|
|
J.S.Yang,
S.Y.Lee,
S.Spanò,
H.Gad,
L.Zhang,
Z.Nie,
M.Bonazzi,
D.Corda,
A.Luini,
and
V.W.Hsu
(2005).
A role for BARS at the fission step of COPI vesicle formation from Golgi membrane.
|
| |
EMBO J, 24,
4133-4143.
|
|
|
|
|
|
|
L.G.Smith,
and
D.G.Oppenheimer
(2005).
Spatial control of cell expansion by the plant cytoskeleton.
|
| |
Annu Rev Cell Dev Biol, 21,
271-295.
|
|
|
|
|
|
|
M.Bonazzi,
S.Spanò,
G.Turacchio,
C.Cericola,
C.Valente,
A.Colanzi,
H.S.Kweon,
V.W.Hsu,
E.V.Polishchuck,
R.S.Polishchuck,
M.Sallese,
T.Pulvirenti,
D.Corda,
and
A.Luini
(2005).
CtBP3/BARS drives membrane fission in dynamin-independent transport pathways.
|
| |
Nat Cell Biol, 7,
570-580.
|
|
|
|
|
|
|
P.Struffi,
and
D.N.Arnosti
(2005).
Functional interaction between the Drosophila knirps short range transcriptional repressor and RPD3 histone deacetylase.
|
| |
J Biol Chem, 280,
40757-40765.
|
|
|
|
|
|
|
C.Hidalgo Carcedo,
M.Bonazzi,
S.Spanò,
G.Turacchio,
A.Colanzi,
A.Luini,
and
D.Corda
(2004).
Mitotic Golgi partitioning is driven by the membrane-fissioning protein CtBP3/BARS.
|
| |
Science, 305,
93-96.
|
|
|
|
|
|
|
G.van Meer,
and
H.Sprong
(2004).
Membrane lipids and vesicular traffic.
|
| |
Curr Opin Cell Biol, 16,
373-378.
|
|
|
|
|
|
|
M.Sutrias-Grau,
and
D.N.Arnosti
(2004).
CtBP contributes quantitatively to Knirps repression activity in an NAD binding-dependent manner.
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| |
Mol Cell Biol, 24,
5953-5966.
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N.Altan-Bonnet,
R.Sougrat,
and
J.Lippincott-Schwartz
(2004).
Molecular basis for Golgi maintenance and biogenesis.
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| |
Curr Opin Cell Biol, 16,
364-372.
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|
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R.Alpatov,
G.C.Munguba,
P.Caton,
J.H.Joo,
Y.Shi,
Y.Shi,
M.E.Hunt,
and
S.P.Sugrue
(2004).
Nuclear speckle-associated protein Pnn/DRS binds to the transcriptional corepressor CtBP and relieves CtBP-mediated repression of the E-cadherin gene.
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| |
Mol Cell Biol, 24,
10223-10235.
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C.C.Fjeld,
W.T.Birdsong,
and
R.H.Goodman
(2003).
Differential binding of NAD+ and NADH allows the transcriptional corepressor carboxyl-terminal binding protein to serve as a metabolic sensor.
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| |
Proc Natl Acad Sci U S A, 100,
9202-9207.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
