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1
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0029781509
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Functional interaction of β-catenin with the transcription factor LEF-1
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of outstanding interest. These authors discovered the interaction between β-catenin and LEF-1 in a yeast two-hybrid screen, using β-catenin as a bait. They show that a ternary complex forms between β-catenin and DNA-bound LEF-1, and that LEF-1 overexpression in Xenopus embryos produces early axis duplication, that is a Wnt-1 overexpression phenotype, in a manner dependent on β-catenin.
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Behrens J, von Kies JP, Kühl M, Bruhn L, Wedlich D, Grosschedl R, Birchmeier W. Functional interaction of β-catenin with the transcription factor LEF-1. of outstanding interest Nature. 382:1996;638-642 These authors discovered the interaction between β-catenin and LEF-1 in a yeast two-hybrid screen, using β-catenin as a bait. They show that a ternary complex forms between β-catenin and DNA-bound LEF-1, and that LEF-1 overexpression in Xenopus embryos produces early axis duplication, that is a Wnt-1 overexpression phenotype, in a manner dependent on β-catenin.
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(1996)
Nature
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Behrens, J.1
Von Kies, J.P.2
Kühl, M.3
Bruhn, L.4
Wedlich, D.5
Grosschedl, R.6
Birchmeier, W.7
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2
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0001003110
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XTcf-3 transcription factor mediates β-catenin-axis formation in Xenopus embryos
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of outstanding interest. These authors report the isolation of XTcf-3, a TCF homologue expressed in early Xenopus embryos. The authors show that XTcf-3 binds to β-catenin and activates transcription in a β-catenin-dependent way. They also demonstrate that a dominant-negative form of XTcf-3 which cannot bind β-catenin suppresses axis formation in Xenopus embryos, implicating a function of XTcf-3 in responding to β-catenin signalling.
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Molenaar M, van de Wetering M, Oosterwegel M, Peterson-Maduro J, Godsave S, Korinek V, Roose J, Destrée O, Clevers H. XTcf-3 transcription factor mediates β-catenin-axis formation in Xenopus embryos. of outstanding interest Cell. 86:1996;391-399 These authors report the isolation of XTcf-3, a TCF homologue expressed in early Xenopus embryos. The authors show that XTcf-3 binds to β-catenin and activates transcription in a β-catenin-dependent way. They also demonstrate that a dominant-negative form of XTcf-3 which cannot bind β-catenin suppresses axis formation in Xenopus embryos, implicating a function of XTcf-3 in responding to β-catenin signalling.
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(1996)
Cell
, vol.86
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Molenaar, M.1
Van De Wetering, M.2
Oosterwegel, M.3
Peterson-Maduro, J.4
Godsave, S.5
Korinek, V.6
Roose, J.7
Destrée, O.8
Clevers, H.9
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3
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0345343608
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Nuclear localization of β-catenin by interaction with transcription factor LEF-1
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of outstanding interest. Lef1 was found among genes whose expression was induced in mouse embryonic stem cells with elevated free β-catenin. It is shown that LEF-1 binds β-catenin, that it can import β-catenin into the nucleus and that overexpression of LEF-1 in Xenopus embryos causes early axis duplication.
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Huber O, Korn R, McLaughlin J, Ohsugi M, Herrmann BG, Kemler R. Nuclear localization of β-catenin by interaction with transcription factor LEF-1. of outstanding interest Mech Dev. 59:1996;3-10 Lef1 was found among genes whose expression was induced in mouse embryonic stem cells with elevated free β-catenin. It is shown that LEF-1 binds β-catenin, that it can import β-catenin into the nucleus and that overexpression of LEF-1 in Xenopus embryos causes early axis duplication.
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Mech Dev
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Huber, O.1
Korn, R.2
McLaughlin, J.3
Ohsugi, M.4
Herrmann, B.G.5
Kemler, R.6
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4
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LEF-1, a nuclear factor coordinating signaling inputs from wingless and decapentaplegic
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of outstanding interest. The Wingless response sequence in the midgut enhancer of Ubx, a Wingless target gene, is identified as a binding site for LEF-1. The authors demonstrate that LEF-1 activates transcription in the fly embryo, and that it functions in an armadillo-dependent way to cause shaggy-like phenotypes. Evidence is a provided that dTCF acts through the Ubx enhancer in a context-dependent way, co-operating with the CRE-binding protein that responds to Decapentaplegic signalling.
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Riese J, Yu X, Munnerlyn A, Eresh S, Hsu S-C, Grosschedl R, Bienz M. LEF-1, a nuclear factor coordinating signaling inputs from wingless and decapentaplegic. of outstanding interest Cell. 88:1997;777-787 The Wingless response sequence in the midgut enhancer of Ubx, a Wingless target gene, is identified as a binding site for LEF-1. The authors demonstrate that LEF-1 activates transcription in the fly embryo, and that it functions in an armadillo-dependent way to cause shaggy-like phenotypes. Evidence is a provided that dTCF acts through the Ubx enhancer in a context-dependent way, co-operating with the CRE-binding protein that responds to Decapentaplegic signalling.
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(1997)
Cell
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Riese, J.1
Yu, X.2
Munnerlyn, A.3
Eresh, S.4
Hsu S-C5
Grosschedl, R.6
Bienz, M.7
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5
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0030999806
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Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF
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of outstanding interest. Isolation of dTCF, the Drosophila homologue of LEF-1, and description of the loss-of-function phenotypes in fly embryos. These phenotypes mimic armadillo and wingless phenotypes, strongly indicating that dTCF is an obligatory target factor for Wingless signalling. Epistasis experiments place dTCF downstream of Armadillo.
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Van de Wetering M, Cavallo R, Dooijes D, van Beest M, van Es J, Loureiro J, Ypma A, Hursh D, Jones T, Bejsovec A, et al. Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF. of outstanding interest Cell. 88:1997;789-799 Isolation of dTCF, the Drosophila homologue of LEF-1, and description of the loss-of-function phenotypes in fly embryos. These phenotypes mimic armadillo and wingless phenotypes, strongly indicating that dTCF is an obligatory target factor for Wingless signalling. Epistasis experiments place dTCF downstream of Armadillo.
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(1997)
Cell
, vol.88
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Van De Wetering, M.1
Cavallo, R.2
Dooijes, D.3
Van Beest, M.4
Van Es, J.5
Loureiro, J.6
Ypma, A.7
Hursh, D.8
Jones, T.9
Bejsovec, A.10
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6
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0031043238
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Pangolin encodes a Lef-1 homologue that acts downstream of Armadillo to transduce the Wingless signal in Drosophila
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of outstanding interest. Identification of pangolin as a suppressor of a Wingless overexpression phenotype in the fly eye. The authors show that pangolin encodes a Drosophila LEF-1 homologue and that pangolin hypomorphic mutations mimic loss of wingless function in several developmental contexts. Point mutations are identified in the amino-terminal domain of Pangolin which reduce binding to Armadillo.
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Brunner E, Peter O, Schweizer L, Basler K. pangolin encodes a Lef-1 homologue that acts downstream of Armadillo to transduce the Wingless signal in Drosophila. of outstanding interest Nature. 385:1997;829-833 Identification of pangolin as a suppressor of a Wingless overexpression phenotype in the fly eye. The authors show that pangolin encodes a Drosophila LEF-1 homologue and that pangolin hypomorphic mutations mimic loss of wingless function in several developmental contexts. Point mutations are identified in the amino-terminal domain of Pangolin which reduce binding to Armadillo.
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Nature
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Brunner, E.1
Peter, O.2
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Basler, K.4
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Identification and cloning of TCF-1, a T lymphocyte-specific transcription factor containing a sequence-specific HMG box
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Nusse R. A versatile transcriptional effector of Wingless signaling. Cell. 89:1997;321-323.
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0030975671
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-/- colon carcinoma
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of outstanding interest. Isolation of hTcf-4, the T cell factor (TCF) expressed in the human colonic epithelium. The authors show that colon carcinoma cells lacking adenomatous polyposis coli protein (APC) contain a constitutively active hTcf-4/β-catenin complex whose transcriptional activity is abrogated by reintroduction of APC. This study strongly indicates that deregulated TCF is the most common cause of colon cancer.
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-/- colon carcinoma. of outstanding interest Science. 275:1997;1784-1787 Isolation of hTcf-4, the T cell factor (TCF) expressed in the human colonic epithelium. The authors show that colon carcinoma cells lacking adenomatous polyposis coli protein (APC) contain a constitutively active hTcf-4/β-catenin complex whose transcriptional activity is abrogated by reintroduction of APC. This study strongly indicates that deregulated TCF is the most common cause of colon cancer.
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(1997)
Science
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Korinek, V.1
Barker, N.2
Morin, P.J.3
Van Wichen, D.4
De Weger, R.5
Kinzler, K.W.6
Vogelstein, B.7
Clevers, H.8
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20
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0030949463
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Activation of β-catenin-Tcf signaling in colon cancer by mutations in β-catenin or APC
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of outstanding interest. Identification of point mutations in β-catenin from colon carcinoma cells that contain functional APC. It is demonstrated that these mutations, like carboxy-terminal truncations of APC, lead to elevated β-catenin levels and cause deregulated transcriptional activity of TCF. This study identifies β-catenin as an oncogene.
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Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B, Kinzler KW. Activation of β-catenin-Tcf signaling in colon cancer by mutations in β-catenin or APC. of outstanding interest Science. 275:1997;1787-1790 Identification of point mutations in β-catenin from colon carcinoma cells that contain functional APC. It is demonstrated that these mutations, like carboxy-terminal truncations of APC, lead to elevated β-catenin levels and cause deregulated transcriptional activity of TCF. This study identifies β-catenin as an oncogene.
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(1997)
Science
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Morin, P.J.1
Sparks, A.B.2
Korinek, V.3
Barker, N.4
Clevers, H.5
Vogelstein, B.6
Kinzler, K.W.7
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21
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0030900696
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Stabilization of β-catenin by genetic defects in melanoma cell lines
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of outstanding interest. Identification of mutations in β-catenin or APC in a substantial fraction of human melanoma cell lines. As in the colon carcinoma cells, these mutations cause high β-catenin levels and a constitutive LEF-1/β-catenin complex. Thus, TCF deregulation is likely to cause cancer in tissues other than the colon.
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Rubinfeld B, Robbins P, El-Gamil M, Albert I, Porfiri E, Polakis P. Stabilization of β-catenin by genetic defects in melanoma cell lines. of outstanding interest Science. 275:1997;1790-1792 Identification of mutations in β-catenin or APC in a substantial fraction of human melanoma cell lines. As in the colon carcinoma cells, these mutations cause high β-catenin levels and a constitutive LEF-1/β-catenin complex. Thus, TCF deregulation is likely to cause cancer in tissues other than the colon.
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Science
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Rubinfeld, B.1
Robbins, P.2
El-Gamil, M.3
Albert, I.4
Porfiri, E.5
Polakis, P.6
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Induction of a β-catenin-LEF-1 complex by Wnt-1 and transforming mutants of β-catenin
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of outstanding interest. of special interest. This study confirms the data in Korinek 1997, Morin 1997 and Rubinfeld 1997 [19-21], and shows that LEF-1 transcription is induced de novo as a consequence of high β-catenin levels in colon carcinoma cells. This implicates LEF-1 in addition to hTcf-4 in colon tumourigenesis.
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of outstanding interest Porfiri E, Rubinfeld B, Albert I, Hovanes K, Waterman M, Polakis P. Induction of a β-catenin-LEF-1 complex by Wnt-1 and transforming mutants of β-catenin. of special interest Oncogene. 15:1997;2833-2839 This study confirms the data in Korinek 1997, Morin 1997 and Rubinfeld 1997 [19-21], and shows that LEF-1 transcription is induced de novo as a consequence of high β-catenin levels in colon carcinoma cells. This implicates LEF-1 in addition to hTcf-4 in colon tumourigenesis.
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Oncogene
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Porfiri, E.1
Rubinfeld, B.2
Albert, I.3
Hovanes, K.4
Waterman, M.5
Polakis, P.6
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Embryonic axis induction by the Armadillo repeat domain of β-catenin: Evidence for intracellular signaling
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The axis-inducing activity, stability, and subcellular-distribution of β-catenin is regulated in Xenopus embryos by glycogen-synthase kinase-3
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Bienz M. Endoderm induction in Drosophila: the nuclear targets of the inducing signals. Curr Opin Genet Dev. 7:1997;683-688.
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of special interest. Identification of Xenopus siamois as the first known target gene for β-catenin and XTcf-3 in a vertebrate. Mutation of the TCF binding sites within the siamois enhancer not only decreases β-catenin-dependent transcriptional activation in the dorsal Xenopus embryo, but also causes transcriptional derepression in the ventral embryo. This suggests a repressive function of XTcf-3 in unstimulated cells.
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Brannon M, Gomperts M, Sumoy L, Moon RT, Kimelman D. A β-catenin/XTcf-3 complex binds to the siamois promoter to regulate dorsal axis specification in Xenopus. of special interest Genes Dev. 11:1997;2359-2370 Identification of Xenopus siamois as the first known target gene for β-catenin and XTcf-3 in a vertebrate. Mutation of the TCF binding sites within the siamois enhancer not only decreases β-catenin-dependent transcriptional activation in the dorsal Xenopus embryo, but also causes transcriptional derepression in the ventral embryo. This suggests a repressive function of XTcf-3 in unstimulated cells.
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Genes Dev
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Expression cloning of Siamois, a Xenopus homeobox gene expressed in dorsal-vegetal cells of blastulae and able to induce a complete secondary axis
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Binding of Gsk3β to the APC-β-catenin complex and regulation of complex assembly
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of special interest. A biochemical analysis, showing that APC binds to Gsk3β in vivo, that APC is a substrate of Gsk3β in vitro, and that phosphorylation of APC by Gsk3β enhances in vitro binding of APC to β-catenin. These results suggest that APC is a component of the Wnt signalling pathway as its activity might be regulated by Gsk-3.
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Rubinfeld B, Albert I, Porfiri E, Fiol C, Munemitsu S, Polakis P. Binding of Gsk3β to the APC-β-catenin complex and regulation of complex assembly. of special interest Science. 272:1996;1023-1026 A biochemical analysis, showing that APC binds to Gsk3β in vivo, that APC is a substrate of Gsk3β in vitro, and that phosphorylation of APC by Gsk3β enhances in vitro binding of APC to β-catenin. These results suggest that APC is a component of the Wnt signalling pathway as its activity might be regulated by Gsk-3.
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Science
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A Drosophila homolog of the tumor suppressor gene adenomatous polyposis coli down-regulates β-catenin but its zygotic expression is not essential for the regulation of Armadillo
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of special interest. Genetic and reverse genetic approaches are used to demonstrate that C. elegans genes related to Wnt signal transduction components are required for endoderm specification in the early embryo. The regulatory relationships between these components are somewhat surprising: the genetic analysis implies that wrm-1 (worm β-catenin) synergises with apr-1 (worm APC), while both genes antagonise pop-1 (TCF). This is in contrast to the situation in flies and vertebrates (see Figure 1 of my review). Also, mom-5 (a worm frizzled-like gene and putative Wnt receptor) suppresses mom-2 (a worm Wnt), suggesting functional antagonism between these two genes.
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Rocheleau CE, Downs WD, Lin R, Wittmann C, Bei Y, Cha Y-H, Ali M, Priess JR, Mello CC. Wnt signaling and an APC-related gene specify endoderm in early C. elegans embryos. of special interest Cell. 90:1997;707-716 Genetic and reverse genetic approaches are used to demonstrate that C. elegans genes related to Wnt signal transduction components are required for endoderm specification in the early embryo. The regulatory relationships between these components are somewhat surprising: the genetic analysis implies that wrm-1 (worm β-catenin) synergises with apr-1 (worm APC), while both genes antagonise pop-1 (TCF). This is in contrast to the situation in flies and vertebrates (see Figure 1 of my review). Also, mom-5 (a worm frizzled-like gene and putative Wnt receptor) suppresses mom-2 (a worm Wnt), suggesting functional antagonism between these two genes.
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Cell
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Rocheleau, C.E.1
Downs, W.D.2
Lin, R.3
Wittmann, C.4
Bei, Y.5
Cha Y-H6
Ali, M.7
Priess, J.R.8
Mello, C.C.9
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36
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