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* Residue conservation analysis
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Enzyme class:
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Chains A, B:
E.C.?
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Genes Dev
17:2753-2764
(2003)
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PubMed id:
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Crystal structure of a beta-catenin/axin complex suggests a mechanism for the beta-catenin destruction complex.
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Y.Xing,
W.K.Clements,
D.Kimelman,
W.Xu.
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ABSTRACT
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The "beta-catenin destruction complex" is central to canonical Wnt/beta-catenin
signaling. The scaffolding protein Axin and the tumor suppressor adenomatous
polyposis coli protein (APC) are critical components of this complex, required
for rapid beta-catenin turnover. We determined the crystal structure of a
complex between beta-catenin and the beta-catenin-binding domain of Axin
(Axin-CBD). The Axin-CBD forms a helix that occupies the groove formed by the
third and fourth armadillo repeats of beta-catenin and thus precludes the
simultaneous binding of other beta-catenin partners in this region. Our
biochemical studies demonstrate that, when phosphorylated, the 20-amino acid
repeat region of APC competes with Axin for binding to beta-catenin. We propose
that a key function of APC in the beta-catenin destruction complex is to remove
phosphorylated beta-catenin product from the active site.
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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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G.Drechsel,
J.Bergler,
K.Wippel,
N.Sauer,
K.Vogelmann,
and
S.Hoth
(2011).
C-terminal armadillo repeats are essential and sufficient for association of the plant U-box armadillo E3 ubiquitin ligase SAUL1 with the plasma membrane.
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J Exp Bot,
62,
775-785.
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E.M.Kohler,
K.Brauburger,
J.Behrens,
and
J.Schneikert
(2010).
Contribution of the 15 amino acid repeats of truncated APC to beta-catenin degradation and selection of APC mutations in colorectal tumours from FAP patients.
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Oncogene,
29,
1663-1671.
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M.Adamska,
C.Larroux,
M.Adamski,
K.Green,
E.Lovas,
D.Koop,
G.S.Richards,
C.Zwafink,
and
B.M.Degnan
(2010).
Structure and expression of conserved Wnt pathway components in the demosponge Amphimedon queenslandica.
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Evol Dev,
12,
494-518.
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S.A.Kremer,
N.Erdeniz,
W.Peterson-Nedry,
E.A.Swanson,
and
M.Wehrli
(2010).
In vivo analysis in Drosophila reveals differential requirements of contact residues in Axin for interactions with GSK3beta or beta-catenin.
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Dev Biol,
337,
110-123.
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B.T.MacDonald,
K.Tamai,
and
X.He
(2009).
Wnt/beta-catenin signaling: components, mechanisms, and diseases.
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Dev Cell,
17,
9.
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C.Y.Ou,
J.H.Kim,
C.K.Yang,
and
M.R.Stallcup
(2009).
Requirement of cell cycle and apoptosis regulator 1 for target gene activation by Wnt and beta-catenin and for anchorage-independent growth of human colon carcinoma cells.
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J Biol Chem,
284,
20629-20637.
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H.K.Arnold,
X.Zhang,
C.J.Daniel,
D.Tibbitts,
J.Escamilla-Powers,
A.Farrell,
S.Tokarz,
C.Morgan,
and
R.C.Sears
(2009).
The Axin1 scaffold protein promotes formation of a degradation complex for c-Myc.
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EMBO J,
28,
500-512.
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I.V.Chia,
M.J.Kim,
K.Itoh,
S.Y.Sokol,
and
F.Costantini
(2009).
Both the RGS domain and the six C-terminal amino acids of mouse Axin are required for normal embryogenesis.
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Genetics,
181,
1359-1368.
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K.M.Cadigan,
and
M.Peifer
(2009).
Wnt signaling from development to disease: insights from model systems.
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Cold Spring Harbor Perspect Biol,
1,
a002881.
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R.Mo,
T.L.Chew,
M.T.Maher,
G.Bellipanni,
E.S.Weinberg,
and
C.J.Gottardi
(2009).
The terminal region of beta-catenin promotes stability by shielding the Armadillo repeats from the axin-scaffold destruction complex.
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J Biol Chem,
284,
28222-28231.
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A.Klaus,
and
W.Birchmeier
(2008).
Wnt signalling and its impact on development and cancer.
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Nat Rev Cancer,
8,
387-398.
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B.M.McCartney,
and
I.S.Näthke
(2008).
Cell regulation by the Apc protein Apc as master regulator of epithelia.
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Curr Opin Cell Biol,
20,
186-193.
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C.Perez-Plasencia,
A.Duenas-Gonzalez,
and
B.Alatorre-Tavera
(2008).
Second hit in cervical carcinogenesis process: involvement of wnt/beta catenin pathway.
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Int Arch Med,
1,
10.
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G.Upadhyay,
W.Goessling,
T.E.North,
R.Xavier,
L.I.Zon,
and
V.Yajnik
(2008).
Molecular association between beta-catenin degradation complex and Rac guanine exchange factor DOCK4 is essential for Wnt/beta-catenin signaling.
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Oncogene,
27,
5845-5855.
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I.M.Somorjai,
and
A.Martinez-Arias
(2008).
Wingless signalling alters the levels, subcellular distribution and dynamics of Armadillo and E-cadherin in third instar larval wing imaginal discs.
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PLoS ONE,
3,
e2893.
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M.S.Cortese,
V.N.Uversky,
and
A.K.Dunker
(2008).
Intrinsic disorder in scaffold proteins: getting more from less.
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Prog Biophys Mol Biol,
98,
85.
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X.Chen,
J.Yang,
P.M.Evans,
and
C.Liu
(2008).
Wnt signaling: the good and the bad.
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Acta Biochim Biophys Sin (Shanghai),
40,
577-594.
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X.Guo,
A.Ramirez,
D.S.Waddell,
Z.Li,
X.Liu,
and
X.F.Wang
(2008).
Axin and GSK3- control Smad3 protein stability and modulate TGF- signaling.
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Genes Dev,
22,
106-120.
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Y.Su,
C.Fu,
S.Ishikawa,
A.Stella,
M.Kojima,
K.Shitoh,
E.M.Schreiber,
B.W.Day,
and
B.Liu
(2008).
APC is essential for targeting phosphorylated beta-catenin to the SCFbeta-TrCP ubiquitin ligase.
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Mol Cell,
32,
652-661.
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Z.Lin,
C.Gao,
Y.Ning,
X.He,
W.Wu,
and
Y.G.Chen
(2008).
The pseudoreceptor BMP and activin membrane-bound inhibitor positively modulates Wnt/beta-catenin signaling.
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J Biol Chem,
283,
33053-33058.
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I.C.Tsai,
M.Woolf,
D.W.Neklason,
W.W.Branford,
H.J.Yost,
R.W.Burt,
and
D.M.Virshup
(2007).
Disease-associated casein kinase I delta mutation may promote adenomatous polyps formation via a Wnt/beta-catenin independent mechanism.
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Int J Cancer,
120,
1005-1012.
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M.Ritco-Vonsovici,
A.Ababou,
and
M.Horton
(2007).
Molecular plasticity of beta-catenin: new insights from single-molecule measurements and MD simulation.
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Protein Sci,
16,
1984-1998.
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R.L.Daugherty,
and
C.J.Gottardi
(2007).
Phospho-regulation of Beta-catenin adhesion and signaling functions.
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Physiology (Bethesda),
22,
303-309.
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S.Choi,
E.A.Gustafson-Wagner,
Q.Wang,
S.M.Harlan,
H.W.Sinn,
J.L.Lin,
and
J.J.Lin
(2007).
The intercalated disk protein, mXinalpha, is capable of interacting with beta-catenin and bundling actin filaments [corrected].
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J Biol Chem,
282,
36024-36036.
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D.Kimelman,
and
W.Xu
(2006).
beta-catenin destruction complex: insights and questions from a structural perspective.
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Oncogene,
25,
7482-7491.
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F.Tang,
Y.Peng,
J.J.Nau,
E.J.Kauffman,
and
L.S.Weisman
(2006).
Vac8p, an armadillo repeat protein, coordinates vacuole inheritance with multiple vacuolar processes.
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Traffic,
7,
1368-1377.
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G.Zeng,
U.Apte,
A.Micsenyi,
A.Bell,
and
S.P.Monga
(2006).
Tyrosine residues 654 and 670 in beta-catenin are crucial in regulation of Met-beta-catenin interactions.
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Exp Cell Res,
312,
3620-3630.
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H.Clevers
(2006).
Wnt/beta-catenin signaling in development and disease.
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Cell,
127,
469-480.
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J.Sierra,
T.Yoshida,
C.A.Joazeiro,
and
K.A.Jones
(2006).
The APC tumor suppressor counteracts beta-catenin activation and H3K4 methylation at Wnt target genes.
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Genes Dev,
20,
586-600.
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J.N.Jensen,
E.Cameron,
M.V.Garay,
T.W.Starkey,
R.Gianani,
and
J.Jensen
(2005).
Recapitulation of elements of embryonic development in adult mouse pancreatic regeneration.
|
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Gastroenterology,
128,
728-741.
|
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|
|
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M.Fujimuro,
J.Liu,
J.Zhu,
H.Yokosawa,
and
S.D.Hayward
(2005).
Regulation of the interaction between glycogen synthase kinase 3 and the Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen.
|
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J Virol,
79,
10429-10441.
|
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R.Nusse
(2005).
Wnt signaling in disease and in development.
|
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Cell Res,
15,
28-32.
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C.Y.Logan,
and
R.Nusse
(2004).
The Wnt signaling pathway in development and disease.
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Annu Rev Cell Dev Biol,
20,
781-810.
|
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Y.Xing,
W.K.Clements,
I.Le Trong,
T.R.Hinds,
R.Stenkamp,
D.Kimelman,
and
W.Xu
(2004).
Crystal structure of a beta-catenin/APC complex reveals a critical role for APC phosphorylation in APC function.
|
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Mol Cell,
15,
523-533.
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PDB code:
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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
code is
shown on the right.
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}
}
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