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Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3–independent ß-catenin degradation
Lilia Topol,
Xueyuan Jiang,
Hosoon Choi,
Lisa Garrett-Beal,
Peter J. Carolan, and
Yingzi Yang
Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892
Address correspondence to Yingzi Yang, Genetic Disease Research Branch, National Human Genome Research Institute, NIH, 49 Convent Dr., Room 4A68, Bethesda, MD 20892. Tel: (301) 402-2034. Fax: (301) 402-2170. email: yyang{at}nhgri.nih.gov
Abstract:
Wnts are secreted signaling molecules that can transduce theirsignals through several different pathways. Wnt-5a is considereda noncanonical Wnt as it does not signal by stabilizing ß-cateninin many biological systems. We have uncovered a new noncanonicalpathway through which Wnt-5a antagonizes the canonical Wnt pathwayby promoting the degradation of ß-catenin. This pathwayis Siah2 and APC dependent, but GSK-3 and ß-TrCP independent.Furthermore, we provide evidence that Wnt-5a also acts in vivoto promote ß-catenin degradation in regulating mammalianlimb development and possibly in suppressing tumor formation.
Wnt Signaling in Normal and Malignant Hematopoiesis.
W. Lento, K. Congdon, C. Voermans, M. Kritzik, and T. Reya (2013)
Cold Spring Harb Perspect Biol
5, a008011
|Abstract »|Full Text »|PDF »
The Wnt Coreceptor Ryk Regulates Wnt/Planar Cell Polarity by Modulating the Degradation of the Core Planar Cell Polarity Component Vangl2.
P. Andre, Q. Wang, N. Wang, B. Gao, A. Schilit, M. M. Halford, S. A. Stacker, X. Zhang, and Y. Yang (2012)
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Cold Spring Harb Perspect Biol
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The Role of Canonical WNT Signaling Pathway in Oral Carcinogenesis: A Comprehensive Review.
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Targeting of Noncanonical Wnt5a Signaling by AP-1 Blocker Dominant-Negative Jun When It Inhibits Skin Carcinogenesis.
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Rack1 is required for Vangl2 membrane localization and planar cell polarity signaling while attenuating canonical Wnt activity.
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Identification of Predictive Markers of Response to the MEK1/2 Inhibitor Selumetinib (AZD6244) in K-ras-Mutated Colorectal Cancer.
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PNAS
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Carcinogenesis
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M. J. Nemeth, L. Topol, S. M. Anderson, Y. Yang, and D. M. Bodine (2007)
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Endocrinology
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R. J. MacLeod, M. Hayes, and I. Pacheco (2007)
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Mol. Endocrinol.
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Development
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beta-Catenin Signaling Pathway Is Crucial for Bone Morphogenetic Protein 2 to Induce New Bone Formation.
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PNAS
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Development
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WNT Pathways in the Neonatal Ovine Uterus: Potential Specification of Endometrial Gland Morphogenesis by SFRP2.
Sfrp1 and Sfrp2 regulate anteroposterior axis elongation and somite segmentation during mouse embryogenesis.
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Development
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Bioinformatics
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Genes & Dev.
19, 164-175
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Zebrafish Dapper1 and Dapper2 play distinct roles in Wnt-mediated developmental processes.
J. S. Waxman, A. M. Hocking, C. L. Stoick, and R. T. Moon (2004)
Development
131, 5909-5921
|Abstract »|Full Text »|PDF »
Analysis of Wnt Gene Expression in Prostate Cancer: Mutual Inhibition by WNT11 and the Androgen Receptor.
H. Zhu, M. Mazor, Y. Kawano, M. M. Walker, H. Y. Leung, K. Armstrong, J. Waxman, and R. M. Kypta (2004)
Cancer Res.
64, 7918-7926
|Abstract »|Full Text »|PDF »
Wnt/{beta}-catenin signaling is sufficient and necessary for synovial joint formation.
X. Guo, T. F. Day, X. Jiang, L. Garrett-Beal, L. Topol, and Y. Yang (2004)
Genes & Dev.
18, 2404-2417
|Abstract »|Full Text »|PDF »
Multiple Mechanisms for Wnt11-mediated Repression of the Canonical Wnt Signaling Pathway.
P. Maye, J. Zheng, L. Li, and D. Wu (2004)
J. Biol. Chem.
279, 24659-24665
|Abstract »|Full Text »|PDF »
Inhibition of Wnt-1 Signaling Induces Apoptosis in {beta}-Catenin-Deficient Mesothelioma Cells.
L. You, B. He, K. Uematsu, Z. Xu, J. Mazieres, A. Lee, F. McCormick, and D. M. Jablons (2004)
Cancer Res.
64, 3474-3478
|Abstract »|Full Text »|PDF »
Interactions between Sox9 and {beta}-catenin control chondrocyte differentiation.
H. Akiyama, J. P. Lyons, Y. Mori-Akiyama, X. Yang, R. Zhang, Z. Zhang, J. M. Deng, M. M. Taketo, T. Nakamura, R. R. Behringer, et al. (2004)
Genes & Dev.
18, 1072-1087
|Abstract »|Full Text »|PDF »
Wnt5a is required for proper epithelial-mesenchymal interactions in the uterus.
M. Mericskay, J. Kitajewski, and D. Sassoon (2004)
Development
131, 2061-2072
|Abstract »|Full Text »|PDF »
