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Volumn 8, Issue 1, 1998, Pages 95-102

β-catenin: A key mediator of Wnt signaling

Author keywords

[No Author keywords available]

Indexed keywords

BETA CATENIN; LYMPHOID ENHANCER FACTOR 1; PROTEIN; TRANSCRIPTION FACTOR;

EID: 0031888098     PISSN: 0959437X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-437X(98)80068-3     Document Type: Article
Times cited : (682)

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    • of outstanding interest. of special interest. By screening a Drosophila expression library with an antibody against human APC, the authors isolate an APC homolog, called D-APC. Even though D-APC interacts directly with Arm in vitro and reduces β-catenin levels when overexpressed in cells lacking wild-type APC, removal of zygotic D-APC did not alter Arm protein distribution and no phenotypes suggesting an inhibitory role in Wg signaling were observed. These results, in combination with the results in C. elegans [37] and the results in Xenopus [36], suggest a more complex function for APC in Wnt signaling than was previously thought.
    • of outstanding interest Hayashi S, Rubinfeld B, Souza B, Polakis P, Wieschaus E, Levine AJ. 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. of special interest Proc Natl Acad Sci USA. 94:1997;242-247 By screening a Drosophila expression library with an antibody against human APC, the authors isolate an APC homolog, called D-APC. Even though D-APC interacts directly with Arm in vitro and reduces β-catenin levels when overexpressed in cells lacking wild-type APC, removal of zygotic D-APC did not alter Arm protein distribution and no phenotypes suggesting an inhibitory role in Wg signaling were observed. These results, in combination with the results in C. elegans [37] and the results in Xenopus [36], suggest a more complex function for APC in Wnt signaling than was previously thought.
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    • Hayashi, S.1    Rubinfeld, B.2    Souza, B.3    Polakis, P.4    Wieschaus, E.5    Levine, A.J.6
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    • Adenomatous polyposis coli tumor suppressor protein has signaling activity in Xenopus laevis embryos resulting in the induction of an ectopic dorsoanterior axis
    • of outstanding interest. of special interest. Ectopic expression of APC in Xenopus embryos induces a secondary axis, suggesting a positive rather than a negative role for APC in Wnt signaling. This axis induction by APC is dependent on the availability of free β-catenin. These results in conjunction with the work in [37] suggest a more complex role for APC in the Wnt signaling pathway than simply targeting β-catenin for degradation.
    • of outstanding interest Vleminckx K, Wong E, Guger K, Rubinfeld B, Polakis P, Gumbiner BM. Adenomatous polyposis coli tumor suppressor protein has signaling activity in Xenopus laevis embryos resulting in the induction of an ectopic dorsoanterior axis. of special interest J Cell Biol. 136:1997;411-420 Ectopic expression of APC in Xenopus embryos induces a secondary axis, suggesting a positive rather than a negative role for APC in Wnt signaling. This axis induction by APC is dependent on the availability of free β-catenin. These results in conjunction with the work in [37] suggest a more complex role for APC in the Wnt signaling pathway than simply targeting β-catenin for degradation.
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    • Vleminckx, K.1    Wong, E.2    Guger, K.3    Rubinfeld, B.4    Polakis, P.5    Gumbiner, B.M.6
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    • Wnt signaling and an APC-related gene specify endoderm in early C. elegans embryos
    • of outstanding interest. The authors use both a genetic screen and an RNA-mediated interference (RNA) technique to identify genes involved in the specification of endoderm in early C. elegans embryos. The genes described are related to wnt/wingless (mom-2), porcupine (mom-1), frizzled (mom-5), β-catenin/armadillo (wrm-1), and APC (apr-1), all of which have been implicated in the transduction of the Wnt signal in other systems. Unlike in previously studied systems, wrm-1 acts to inhibit the activity of pop-1, a TCF homolog, presumably by facilitating the movement of POP-1 out of the nucleus. Several of these so-called mom mutants also display an abnormal orientation of certain mitotic spindles. pop-1 mutants do not display this effect, thus suggesting that the Wnt signaling pathway affects spindle orientation in a pop-1 independent pathway.
    • Rocheleau C, Downs W, Lin R, Wittmann C, Bei Y, Cha Y-H, Ali M, Priess J, Mello C. Wnt signaling and an APC-related gene specify endoderm in early C. elegans embryos. of outstanding interest Cell. 90:1997;707-716 The authors use both a genetic screen and an RNA-mediated interference (RNA) technique to identify genes involved in the specification of endoderm in early C. elegans embryos. The genes described are related to wnt/wingless (mom-2), porcupine (mom-1), frizzled (mom-5), β-catenin/armadillo (wrm-1), and APC (apr-1), all of which have been implicated in the transduction of the Wnt signal in other systems. Unlike in previously studied systems, wrm-1 acts to inhibit the activity of pop-1, a TCF homolog, presumably by facilitating the movement of POP-1 out of the nucleus. Several of these so-called mom mutants also display an abnormal orientation of certain mitotic spindles. pop-1 mutants do not display this effect, thus suggesting that the Wnt signaling pathway affects spindle orientation in a pop-1 independent pathway.
    • (1997) Cell , vol.90 , pp. 707-716
    • Rocheleau, C.1    Downs, W.2    Lin, R.3    Wittmann, C.4    Bei, Y.5    Cha Y-H6    Ali, M.7    Priess, J.8    Mello, C.9
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    • Analysis of the signaling activities of localization mutants of β-catenin during axis specification in Xenopus
    • of special interest. A membrane-tethered β-catenin is still able to induce a secondary axis in Xenopus even though it fails to enter the nucleus itself. The authors argue that overexpression of this mislocalized β-catenin competes with the endogenous degradation machinery thus permitting accumulation and subsequent nuclear entry of the endogenous β-catenin.
    • Miller J, Moon R. Analysis of the signaling activities of localization mutants of β-catenin during axis specification in Xenopus. of special interest J Cell Biol. 139:1997;229-243 A membrane-tethered β-catenin is still able to induce a secondary axis in Xenopus even though it fails to enter the nucleus itself. The authors argue that overexpression of this mislocalized β-catenin competes with the endogenous degradation machinery thus permitting accumulation and subsequent nuclear entry of the endogenous β-catenin.
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    • Miller, J.1    Moon, R.2
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    • The segment polarity gene armadillo encodes a functionally modular protein that is the Drosophila homolog of human plakoglobin
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    • LEF-1, a nuclear factor coordinating signaling inputs from wingless and decapentaplegic
    • of special interest. LEF-1 activates transcription of Ubx in the midgut by binding to a TCF-binding site in the Wingless-responsive element of the Ubx promoter. Arm forms a stable ternary complex with LEF-1 and DNA and is required for LEF-1-dependent activation. Overexpression of LEF-1 displays similar phenotypes as ubiquitously expressed wingless, demonstrating that LEF-1 overexpression bypasses the Wingless signal. Furthermore, wingless and decapentaplegic signaling work synergistically to affect this process.
    • 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 special interest Cell. 88:1997;777-787 LEF-1 activates transcription of Ubx in the midgut by binding to a TCF-binding site in the Wingless-responsive element of the Ubx promoter. Arm forms a stable ternary complex with LEF-1 and DNA and is required for LEF-1-dependent activation. Overexpression of LEF-1 displays similar phenotypes as ubiquitously expressed wingless, demonstrating that LEF-1 overexpression bypasses the Wingless signal. Furthermore, wingless and decapentaplegic signaling work synergistically to affect this process.
    • (1997) Cell , vol.88 , pp. 777-787
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    • Establishment of the dorso-ventral axis in Xenopus embryos is presaged by early asymmetries in beta-catenin that are modulated by the Wnt signaling pathway
    • of special interest. By careful confocal microscopy, the authors argue that at the two cell stage more cytoplasmic β-catenin has accumulated on the future dorsal side of the Xenopus embryo. By later stages, β-catenin accumulates in dorsal but not ventral nuclei. Based on these results, the authors suggest that β-catenin asymmetries presage and may specify dorsal-ventral differences in gene expression.
    • Larabell CA, Torres M, Rowning BA, Yost C, Miller JR, Wu M, Kimelman D, Moon RT. Establishment of the dorso-ventral axis in Xenopus embryos is presaged by early asymmetries in beta-catenin that are modulated by the Wnt signaling pathway. of special interest J Cell Biol. 136:1997;1123-1136 By careful confocal microscopy, the authors argue that at the two cell stage more cytoplasmic β-catenin has accumulated on the future dorsal side of the Xenopus embryo. By later stages, β-catenin accumulates in dorsal but not ventral nuclei. Based on these results, the authors suggest that β-catenin asymmetries presage and may specify dorsal-ventral differences in gene expression.
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    • Larabell, C.A.1    Torres, M.2    Rowning, B.A.3    Yost, C.4    Miller, J.R.5    Wu, M.6    Kimelman, D.7    Moon, R.T.8
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    • A β-catenin/XTcf-3 complex binds to the Siamois promoter to regulate dorsal axis specification in Xenopus
    • of outstanding interest. The promoter of the dorsalizing homeobox gene siamois in Xenopus is shown to be a direct target of the β-catenin/XTCF-3 complex, thus establishing a link between the Wnt pathway and the activation of genes involved in specifying the dorsal axis. The authors also demonstrate that XTCF-3 in the absence of β-catenin, and hence in the absence of a Wnt signal, can act as a transcriptional repressor. The dorsal activation in combination with ventral repression of the siamois promoter is hypothesized to result in a very restricted pattern of siamois expression.
    • Brannon M, Gomperts M, Sumoy L, Moon R, Kimelman D. A β-catenin/XTcf-3 complex binds to the Siamois promoter to regulate dorsal axis specification in Xenopus. of outstanding interest Genes Dev. 11:1997;2359-2370 The promoter of the dorsalizing homeobox gene siamois in Xenopus is shown to be a direct target of the β-catenin/XTCF-3 complex, thus establishing a link between the Wnt pathway and the activation of genes involved in specifying the dorsal axis. The authors also demonstrate that XTCF-3 in the absence of β-catenin, and hence in the absence of a Wnt signal, can act as a transcriptional repressor. The dorsal activation in combination with ventral repression of the siamois promoter is hypothesized to result in a very restricted pattern of siamois expression.
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    • Wnt signaling polarizes an early C. elegans blastomere to distinguish endoderm from mesoderm
    • of outstanding interest. In a genetic screen in C. elegans for mutants that produce more mesoderm at the expense of endoderm, the authors identify five genes, mom-1 through mom-5. mom-2 encodes a Wnt protein which signals to a neighboring cell to adopt an endoderm fate. In mom-2 mutants, POP-1 - a TCF-related protein, which normally is at relatively low levels in the nucleus of this neighboring cell - accumulates to higher levels, suggesting that mom-2's role is to reduce nuclear levels of POP-1. This result contradicts findings in other systems where TCF is thought to be activated by Wnt signaling. The authors furthermore characterize a mitotic spindle defect in mom mutants and suggest that Wnt signaling regulates cytoskeletal polarity.
    • Thorpe CJ, Schlesinger A, Carter JC, Bowerman B. Wnt signaling polarizes an early C. elegans blastomere to distinguish endoderm from mesoderm. of outstanding interest Cell. 90:1997;695-705 In a genetic screen in C. elegans for mutants that produce more mesoderm at the expense of endoderm, the authors identify five genes, mom-1 through mom-5. mom-2 encodes a Wnt protein which signals to a neighboring cell to adopt an endoderm fate. In mom-2 mutants, POP-1 - a TCF-related protein, which normally is at relatively low levels in the nucleus of this neighboring cell - accumulates to higher levels, suggesting that mom-2's role is to reduce nuclear levels of POP-1. This result contradicts findings in other systems where TCF is thought to be activated by Wnt signaling. The authors furthermore characterize a mitotic spindle defect in mom mutants and suggest that Wnt signaling regulates cytoskeletal polarity.
    • (1997) Cell , vol.90 , pp. 695-705
    • Thorpe, C.J.1    Schlesinger, A.2    Carter, J.C.3    Bowerman, B.4
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    • The role of RhoA in tissue polarity and Frizzled signaling
    • of special interest. The authors demonstrate that hypomorphic alleles of RhoA p21 GTPase give rise to phenotypes that are very similar to those of tissue polarity mutants, namely frizzled and dsh. Genetic evidence is provided that JNK/SAPK-like kinases act in the Fz/RhoA-mediated polarity signaling. This pathway may represent a novel Wnt pathway that does not involve Arm and TCF.
    • Strutt DI, Weber U, Mlodzik M. The role of RhoA in tissue polarity and Frizzled signaling. of special interest Nature. 387:1997;292-295 The authors demonstrate that hypomorphic alleles of RhoA p21 GTPase give rise to phenotypes that are very similar to those of tissue polarity mutants, namely frizzled and dsh. Genetic evidence is provided that JNK/SAPK-like kinases act in the Fz/RhoA-mediated polarity signaling. This pathway may represent a novel Wnt pathway that does not involve Arm and TCF.
    • (1997) Nature , vol.387 , pp. 292-295
    • Strutt, D.I.1    Weber, U.2    Mlodzik, M.3
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    • 0030771851 scopus 로고    scopus 로고
    • Accumulation of Armadillo induced by Wingless, Dishevelled, and dominant negative Zeste-white 3 leads to elevated DE-cadherin in Drosophila Clone 8 wing disc cells
    • of special interest. Activation of the Wingless pathway in Drosophila cell culture by overexpression of dsh or dominant negative zeste-white 3 leads to the transcriptional activation of the DE-cadherin gene. The authors speculate that DE-cadherin is a direct transcriptional target of the β-catenin/Arm-TCF complex and hence of the Wnt pathway. These results demonstrate that Wingless signaling, at least indirectly, can modulate cell adhesion.
    • Yanagawa S, Lee J-S, Haruna T, Oda H, Uemura T, Takeichi M, Ishimoto A. Accumulation of Armadillo induced by Wingless, Dishevelled, and dominant negative Zeste-white 3 leads to elevated DE-cadherin in Drosophila Clone 8 wing disc cells. of special interest J Biol Chem. 272:1997;25243-25251 Activation of the Wingless pathway in Drosophila cell culture by overexpression of dsh or dominant negative zeste-white 3 leads to the transcriptional activation of the DE-cadherin gene. The authors speculate that DE-cadherin is a direct transcriptional target of the β-catenin/Arm-TCF complex and hence of the Wnt pathway. These results demonstrate that Wingless signaling, at least indirectly, can modulate cell adhesion.
    • (1997) J Biol Chem , vol.272 , pp. 25243-25251
    • Yanagawa, S.1    Lee J-S2    Haruna, T.3    Oda, H.4    Uemura, T.5    Takeichi, M.6    Ishimoto, A.7
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    • Binding to cadherins antagonizes the signaling activity of β-catenin during axis formation in Xenopus
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    • Fagotto, F.1    Funayama, N.2    Gluck, U.3    Gumbiner, B.M.4


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