Crystal structure of a β-catenin/Axin complex suggests a mechanism for the β-catenin destruction complex
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The “β-catenin destruction complex” is central to canonical Wnt/β-catenin signaling. The scaffolding protein Axin and the tumor suppressor adenomatous polyposis coli protein (APC) are critical components of this complex, required for rapid β-catenin turnover. We determined the crystal structure of a complex between β-catenin and the β-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 β-catenin and thus precludes the simultaneous binding of other β-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 β-catenin. We propose that a key function of APC in the β-catenin destruction complex is to remove phosphorylated β-catenin product from the active site.
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“product is also an axin-binding partner and is thought to remove NH2 terminally phosphorylated β-catenin from the axin complex for transfer to the degradation machinery (84).”
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“In agreement with the in vitro data, MUC1-CD also formed complexes with h-catenin(101-575) and h-catenin(301-575), but not with h-catenin( 1-101 ) or h-catenin(101- 301) (Supplementary Fig. S1E).”
BackgroundWnt Stabilization of β-Catenin Reveals Principles for Morphogen Receptor-Scaffold Assemblies
Kim, S., Huang, H., Zhao, M., Zhang, X., Zhang, A., Semonov, M. V., MacDonald, B. T., Zhang, X., Abreu, J. G., Peng, L., et al. (2013) · Science · doi:10.1126/science.1232389 · Cited by 230 · see citing works
“The β-catenin-binding α-helix, which is the only visible structure from a β-catenin/Axin-BCD (Xenopus) co-crystal (34), is shown above the alignment as a red-colored rod.”
InfluentialCorpet, D. E., & Pierre, F. (2005) · European Journal of Cancer · doi:10.1016/j.ejca.2005.06.006 · Cited by 230 · see citing works
“Axin promotes βcatenin phosphorylation that mediates its degradation in the proteasome (8).”
BackgroundDrugging Wnt signalling in cancer
Polakis, P. G. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.126 · Cited by 229 · see citing works
“…by sequence, cadherin, APC and ICAT, another inhibitor of b -catenin, share with TCF a chemically conserved motif within its extended region, such that the four proteins bind competitively to b -catenin (Eklof Spink et al , 2001; Huber and Weis, 2001; Graham et al , 2002; Xing et al , 2003).”
Qin, K. H., Yu, M. S., Fan, J., Wang, H., Zhao, P., Zhao, G., Zeng, W., Chen, C., Wang, Y., Wang, A., et al. (2023) · Genes & Diseases · doi:10.1016/j.gendis.2023.01.030 · Cited by 226 · see citing works
Wnt/beta-Catenin Signaling and Small Molecule Inhibitors
Voronkov, A. E., & Krauss, S. J. K. (2012) · Current Pharmaceutical Design · doi:10.2174/138161213804581837 · Cited by 224 · see citing works
The way Wnt works: Components and mechanism
Saito‐Diaz, K., Chen, T. W., Wang, X., Thorne, C. A., Wallace, H. A., Page, A. W., & Lee, E. N. (2012) · Growth Factors · doi:10.3109/08977194.2012.752737 · Cited by 215 · see citing works
“…repeats form a positively charged groove that mediates the interaction of b-catenin with other components of the Wnt pathway [e.g. APC, Axin, and T-cell factor (TCF)/LEF] as well as with E-cadherin (Huber et al. 1997; Graham et al. 2000; Huber and Weis 2001; Xing et al. 2003; Xing et al. 2004).”
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Crystal Structure of a Full-Length β-Catenin
Xing, Y., Takemaru, K., Liu, J., Berndt, J. D., Zheng, J., Moon, R. T., & Xu, W. (2008) · Structure · doi:10.1016/j.str.2007.12.021 · Cited by 214 · see citing works
Self-citationWnt/Beta-Catenin Signaling Regulation and a Role for Biomolecular Condensates
Schaefer, K. N., & Peifer, M. A. (2019) · Developmental Cell · doi:10.1016/j.devcel.2019.01.025 · Cited by 194 · see citing works
“The dispensability of APCs βCat binding sites is likely because Axin also plays a role in cytoplasmic retention of βCat in Drosophila (Tolwinski and Wieschaus, 2001), via the single βCat binding site in Axin’s intrinsically disordered region (Xing et al., 2003).”
BackgroundInhibition of GSK3 by Wnt signalling – two contrasting models
Metcalfe, C., & Bienz, M. (2011) · Journal of Cell Science · doi:10.1242/jcs.091991 · Cited by 181 · see citing works
“Furthermore, the high affinity of APC for b-catenin also depends on its phosphorylation by GSK3 (Ha et al., 2004; Rubinfeld et al., 1996; Xing et al., 2003).”
BackgroundAPC Is Essential for Targeting Phosphorylated β-Catenin to the SCFβ-TrCP Ubiquitin Ligase
Su, Y., Fu, C., Ishikawa, S., Stella, A., Kojima, M., Shitoh, K., Schreiber, E. M., Day, B. W., & Liu, B. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.10.023 · Cited by 174 · see citing works
“This model supports a previously proposed hypothesis that phosphorylated b-catenin must be turned over to APC before it is released from the kinase complex (Xing et al., 2003, 2004).”
Messing up disorder: how do missense mutations in the tumor suppressor protein APC lead to cancer?
Minde, D., Anvarian, Z., Rüdiger, S., & Maurice, M. M. (2011) · Molecular Cancer · doi:10.1186/1476-4598-10-101 · Cited by 162 · see citing works
“catenin, whereas unphosphorylated does not [21,25].”
Regulation of Wnt/β‐catenin signaling by protein kinases
Verheyen, E. M., & Gottardi, C. J. (2009) · Developmental Dynamics · doi:10.1002/dvdy.22019 · Cited by 158 · see citing works
“DNA binding factors (Graham et al., 2000; von Kries et al., 2000; Huber and Weis, 2001; Xing et al., 2003).”
Mechanistic insights into Wnt–β-catenin pathway activation and signal transduction
Maurice, M. M., & Angers, S. (2025) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00823-y · Cited by 161 · see citing works
“indicating that these interactions do not occur simultaneously 223,238,250 .”
Thermodynamics of β-Catenin-Ligand Interactions
Choi, H., Huber, A. H., & Weis, W. I. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m511338200 · Cited by 157 · see citing works
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Targeting the β-catenin nuclear transport pathway in cancer
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Direct targeting of β ‐catenin in the Wnt signaling pathway: Current progress and perspectives
Wang, Z., Li, Z., & Ji, H. (2021) · Medicinal Research Reviews · doi:10.1002/med.21787 · Cited by 144 · see citing works
AXIN1 and AXIN2 variants in gastrointestinal cancers
Mazzoni, S. M., & Fearon, E. R. (2014) · Cancer Letters · doi:10.1016/j.canlet.2014.09.018 · Cited by 140 · see citing works
“These mutations contribute to CRC development by stabilizing the “free” signaling pool of β-catenin via disruption of the “β-catenin destruction complex”, which includes the APC (adenomatous polyposis coli) [2–4], AXIN1 [5–7], AXIN2 [8,9], and GSK3β proteins [10,11].”
BackgroundAdamska, M., Larroux, C., Adamski, M., Green, K., Lovas, E., Koop, D., Richards, G. S., Zwafink, C., & Degnan, B. M. (2010) · Evolution & Development · doi:10.1111/j.1525-142x.2010.00435.x · Cited by 139 · see citing works
“The domains and motifs responsible for interactions of Axin with b-catenin, GSK3, and APC have been experimentally determined (Ikeda et al. 1998; Fagotto et al. 1999; Jho et al. 1999; Salic et al. 2000; Spink et al. 2000; Xing et al. 2003).”
BackgroundCell regulation by the Apc protein
McCartney, B. M., & Näthke, I. S. (2008) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2008.02.001 · Cited by 137 · see citing works
Fu, Y., Huang, B., Shi, Z., Han, J., Wang, Y., Huangfu, J., & Wu, W. (2013) · EMBO Molecular Medicine · doi:10.1002/emmm.201202218 · Cited by 120 · see citing works
“In the absence of Wnt ligand, b -catenin is captured by the scaffold protein, Axin, which facilitates sequential phosphorylation by casein kinase 1 (CK1) and glycogen synthase kinase 3 b (GSK3 b ) in the destruction complex (Liu et al, 2002; Xing et al, 2003).”
The Axin1 scaffold protein promotes formation of a degradation complex for c‐Myc
Arnold, H., Zhang, X., Daniel, C. J., Tibbitts, D., Escamilla‐Powers, J. R., Farrell, A., Tokarz, S. A., Morgan, C. W., & Sears, R. C. (2009) · The EMBO Journal · doi:10.1038/emboj.2008.279 · Cited by 117 · see citing works
“The adenomatous polyposis coli (APC) gene product has a critical function in the recruitment and turnover of b-catenin on the Axin1 scaffold protein (Xing et al, 2003).”
BackgroundResultPhosphorylation-Dependent Regulation of WNT/Beta-Catenin Signaling
Shah, K., & Kazi, J. U. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.858782 · Cited by 116 · see citing works
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β‐catenin as a potential key target for tumor suppression
Fu, Y., Zheng, S., An, N., Athanasopoulos, T., Popplewell, L. J., Liang, A., Li, K., Hu, C., & Zhu, Y. (2011) · International Journal of Cancer · doi:10.1002/ijc.26102 · Cited by 101 · see citing works
“It has been reported that the phosphorylated N-terminal of b-catenin represents the recognition site for b-TrCP.61 Phosphorylation of APC by GSK3b and CK1 induces a conformational change that allows the 20-amino acid repeat region of APC to compete with Axin for binding to b-catenin, already phosphorylated by GSK3b an…”
BackgroundSignaling Pathways in Thyroid Cancer and Their Therapeutic Implications
Jin, S., Borkhuu, O., Bao, W., & Yang, Y. (2016) · Journal of Clinical Medicine Research · doi:10.14740/jocmr2480w · Cited by 100 · see citing works
“Wnt pathway includes canonical Wnt pathway (Wnt-β-catenin pathway) and non-canonical pathway (WntCa2+ or Wnt-NK pathway) [145].”
BackgroundMolecular regulation and pharmacological targeting of the β‐catenin destruction complex
van Kappel, E. C., & Maurice, M. M. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13922 · Cited by 88 · see citing works
“Crystal structures of axin – β -catenin and axin – GSK3 complexes show that the disordered axin segments involved turn into helices upon binding (Dajani et al., 2003; Xing et al., 2003).”
Tyrosine residues 654 and 670 in β-catenin are crucial in regulation of Met–β-catenin interactions
Zeng, G., Apte, U. M., Micsenyi, A., et al. (2006) · Experimental Cell Research · doi:10.1016/j.yexcr.2006.08.003 · Cited by 93 · see citing works
“Although crystal structure like the ones described previously would be needed to determine this, we examined the amino acid sequence around the residues 654 and 670 [36,38].”
Agelastatin A: a novel inhibitor of osteopontin-mediated adhesion, invasion, and colony formation
Mason, C. K., McFarlane, S., Johnston, P. G., Crowe, P., Erwin, P. J., Domostoj, M. M., Campbell, F. C., Manaviazar, S., Hale, K. J., & El‐Tanani, M. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-07-2251 · Cited by 93 · see citing works
“Genes already known or suspected to have a down-regulatory effect on h-catenin-mediated signaling include APC, axin (40), conductin/axil, y-TRCP (41), DAPPER (42), NOTCH1 (43), PPA2 (44), presenilin (40), TLE/Groucho, TSC1/2 (45), tuberin-hamartin (46), thyroid hormone receptor (47), and p300/CRBP (48).”
BackgroundRoberts, D. M., Pronobis, M. I., Poulton, J. S., Waldmann, J. D., Stephenson, E. M., Hanna, S., & Peifer, M. A. (2011) · Molecular Biology of the Cell · doi:10.1091/mbc.e10-11-0871 · Cited by 90 · see citing works
“Comparing ßcat localization in wild type and APC mutant cells and tissues suggested that APC and Axin can retain ßcat in the cytoplasm (Tolwinski and Wieschaus, 2001; Krieghoff et al., 2006; McCartney et al., 2006).”
BackgroundInfluentialZhang, Q., Yang, X., Wu, J., Ye, S., Gong, J., Cheng, W. M., Luo, Z., Yu, J., Liu, Y., Zeng, W., et al. (2023) · Cell Discovery · doi:10.1038/s41421-022-00515-x · Cited by 88 · see citing works
Phage Selection of Chemically Stabilized α-Helical Peptide Ligands
Diderich, P., Bertoldo, D., Dessen, P., Maola, K. M. G., Pizzitola, I., Held, W., Huelsken, J., & Heinis, C. (2016) · ACS Chemical Biology · doi:10.1021/acschembio.5b00963 · Cited by 87 · see citing works
CK2 Controls the Recruitment of Wnt Regulators to Target Genes In Vivo
Wang, S., & Jones, K. A. (2006) · Current Biology · doi:10.1016/j.cub.2006.09.034 · Cited by 86 · see citing works
Premise and peril of Wnt signaling activation through GSK-3β inhibition
Law, S. M., & Zheng, J. (2022) · iScience · doi:10.1016/j.isci.2022.104159 · Cited by 85 · see citing works
“Axin also plays an important role in bringing b-catenin and GSK-3b together so that the phosphorylation and subsequent b-catenin can occur in states where there is no Wnt agonist available (Xing et al., 2003).”
BackgroundThe Third 20 Amino Acid Repeat Is the Tightest Binding Site of APC for β-Catenin
Liu, J., Xing, Y., Hinds, T. R., Zheng, J., & Xu, W. (2006) · Journal of Molecular Biology · doi:10.1016/j.jmb.2006.04.064 · Cited by 83 · see citing works
Self-citationSET7/9 regulates cancer cell proliferation by influencing β‐catenin stability
Shen, C., Wang, D., Liu, X., Gu, B., Du, Y., Wei, F., Cao, L., Song, B., Lu, X., Yang, Q., et al. (2015) · The FASEB Journal · doi:10.1096/fj.15-273540 · Cited by 82 · see citing works
“In addition, the phosphorylation of b-catenin at Ser45 by casein kinase (CK)-1a, which primes phosphorylation, induces subsequent phosphorylation by glycogen synthase kinase (GSK)-3b at residues Thr41, Ser37, and Ser33 (15, 16).”
BackgroundInfluentialEnhancing the Cell Permeability of Stapled Peptides with a Cyclic Cell-Penetrating Peptide
Dougherty, P. G., Wen, J., Pan, X., Koley, A., Ren, J.-G., Sahni, A., Basu, R., Salim, H., Kubi, G. A., Qian, Z., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00456 · Cited by 83 · see citing works
Therapeutic stapled peptides: Efficacy and molecular targets
Li, Y., Wu, M., Fu, Y., Xue, J., Yuan, F., Qu, T., Rissanou, A. N., Wang, Y., Li, X., & Hu, H. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107137 · Cited by 85 · see citing works
Xu, P., Ianes, C., Gärtner, F., Liu, C., Burster, T., Bakulev, V. A., Rachidi, N., Knippschild, U., & Bischof, J. (2019) · Gene · doi:10.1016/j.gene.2019.144005 · Cited by 79 · see citing works
Multifunctional arm repeat domains in plants.
Samuel, M., Salt, J. N., Shiu, S., & Goring, D. (2006) · International Review of Cytology · doi:10.1016/s0074-7696(06)53001-3 · Cited by 76 · see citing works
“…its diVerent binding partners, cadherin, TCF, APC, and Axin, have been solved, and interestingly, the binding partners interact with diVerent, but overlapping, regions in the b‐catenin Arm repeat domain (Graham et al., 2000; Harris and Peifer, 2005; Huber and Weis, 2001; Xing et al., 2003, 2004).”
BackgroundCatrow, J. L., Zhang, Y., Zhang, M., & Ji, H. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b00223 · Cited by 83 · see citing works
Second hit in cervical carcinogenesis process: involvement of wnt/beta catenin pathway
Pérez‐Plasencia, C., Dueñas‐González, A., & Alatorre, B. (2008) · International Archives of Medicine · doi:10.1186/1755-7682-1-10 · Cited by 78 · see citing works
“When β-catenin binds to APC, it displaces the union of axin because the binding affinity of β-catenin increases dramatically upon phosphorylation and because the binding motifs of APC to axin and β-catenin overlap [47].”
BackgroundThe Evolutionary Origin of Epithelial Cell–Cell Adhesion Mechanisms
Miller, P. W., Clarke, D. N., Weis, W. I., Lowe, C. J., & Nelson, W. J. (2013) · Current topics in membranes · doi:10.1016/b978-0-12-417027-8.00008-8 · Cited by 76 · see citing works
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Lin, Z., Gao, C., Ning, Y., He, X., Wu, W., & Chen, Y. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m804039200 · Cited by 73 · see citing works
de la Roche, M., Ibrahim, A. E. K., Mieszczanek, J., & Bienz, M. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-2682 · Cited by 71 · see citing works
An Oncogenic Hub: β-Catenin as a Molecular Target for Cancer Therapeutics
Takemaru, K., Ohmitsu, M., & Li, F. Q. (2008) · Handbook of experimental pharmacology · doi:10.1007/978-3-540-72843-6_11 · Cited by 70 · see citing works
Bala, P., Rennhack, J. P., Aitymbayev, D., Morris, C. X., Moyer, S. M., Duronio, G. N., Doan, K. T., Li, Z., Liang, X., Hornick, J. L., et al. (2023) · Science Advances · doi:10.1126/sciadv.adf0927 · Cited by 67 · see citing works
Upadhyay, G., Goessling, W., North, T. E., Xavier, R. J., Zon, L. I., & Yajnik, V. (2008) · Oncogene · doi:10.1038/onc.2008.202 · Cited by 65 · see citing works
“In the literature, phosphorylated APC has been shown to be more efficient in b-catenin binding (Xing et al., 2003).”
BackgroundEnzo, M. V., Rastrelli, M., Rossi, C. R., Hladnik, U., & Segat, D. (2015) · Molecular and Cellular Therapies · doi:10.1186/s40591-015-0038-2 · Cited by 64 · see citing works
“APC can be phosphorylated by CK1/GSK3 increasing its affinity for the same β-catenin domain as Axin, suggesting the role of APC in removing the phosphorylated β-catenin molecules from the complex [20,22,62].”
Ou, C. Y., Kim, J. H., Yang, C. K., & Stallcup, M. R. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.014332 · Cited by 64 · see citing works
Structural basis of coactivation of liver receptor homolog-1 by β-catenin
Yumoto, F., Nguyen, P., Sablin, E. P., Baxter, J. D., Webb, P., & Fletterick, R. J. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1117036108 · Cited by 63 · see citing works
“X-ray structures of the ARM have been determined with interacting fragments of TCF-4 (41, 42), inhibitor of beta-catenin and TCF-4 (ICAT) (43), Axin (44), B-cell chronic lymphocytic leukemia/lymphoma 9 (BCL9) (45), and others (37, 38).”
MethodFang, W., Chen, W.-W., Fu, A. K. Y., & Ip, N. Y. (2013) · Neuron · doi:10.1016/j.neuron.2013.06.017 · Cited by 61 · see citing works
“Intriguingly, blocking the interaction between nuclear Axin and b-catenin by expressing the Axin point mutant (CIDm) that was unable to bind b-catenin in the nucleus (Xing et al., 2003) inhibited neuronal differentiation and maintained the NPC pool (Figures 7E and 7F), particularly IPs (Figures S7F and S7G).”
BackgroundMethodStratford, E. W., Daffinrud, J., Munthe, E., Castro, R., Waaler, J., Krauss, S. J. K., & Myklebost, O. (2013) · Cancer Medicine · doi:10.1002/cam4.170 · Cited by 61 · see citing works
“b-catenin associates with the DC, is phosphorylated by CK1-a and GSK3b [10–12], and subsequently ubiquitinated and degraded [13, 14].”
BackgroundKoelman, E. M. R., Yeste-Vázquez, A., & Grossmann, T. N. (2022) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2022.116920 · Cited by 63 · see citing works
Fujimuro, M., Liu, J., Zhu, J. K., Yokosawa, H., & Hayward, S. D. (2005) · Journal of Virology · doi:10.1128/jvi.79.16.10429-10441.2005 · Cited by 60 · see citing works
“The lower level of phosphorylation supported by CKI may reflect fewer CKI priming sites in LANA(1-340) than for MAPK or, alternatively, CKI priming may be underestimated.”
BackgroundMethodInfluentialThe Role of CTNNB1 in Endometrial Cancer
Ledinek, Ž., Sobočan, M., & Knez, J. (2022) · Disease Markers · doi:10.1155/2022/1442441 · Cited by 61 · see citing works
“It binds with axin on Thr257, Ile296, Ser250, and Trp338 residues [37], none of which were found to be mutated in EC.”
Backgroundvan Leeuwen, I. M. M., Byrne, H. M., Jensen, O. E., & King, J. R. (2007) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2007.01.019 · Cited by 59 · see citing works
Critical Scaffolding Regions of the Tumor Suppressor Axin1 Are Natively Unfolded
Noutsou, M., Duarte, A. M. S., Anvarian, Z., Didenko, T., Minde, D. P., Kuper, I., de Ridder, I., Oikonomou, C., Friedler, A., Boelens, R., et al. (2011) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.11.013 · Cited by 58 · see citing works
Wnt signaling: the good and the bad
Chen, X., Yang, J., Evans, P. M., & Liu, C. (2008) · Acta Biochimica et Biophysica Sinica · doi:10.1111/j.1745-7270.2008.00440.x · Cited by 56 · see citing works
“The structure of part of this destruction complex has been solved [103–112].”
BackgroundDrechsel, G., Bergler, J., Wippel, K., et al. (2010) · Journal of Experimental Botany · doi:10.1093/jxb/erq313 · Cited by 58 · see citing works
“Scale bars in E and F represent 50 lm. 2000; Huber and Weis, 2001; Xing et al., 2003, 2004).”
BackgroundVac8p, an Armadillo Repeat Protein, Coordinates Vacuole Inheritance With Multiple Vacuolar Processes
Tang, F., Peng, Y., Nau, J. J., et al. (2006) · Traffic · doi:10.1111/j.1600-0854.2006.00458.x · Cited by 56 · see citing works
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Identification and in vivo role of the Armadillo-Legless interaction
Hoffmans, R., & Basler, K. (2004) · Development · doi:10.1242/dev.01296 · Cited by 54 · see citing works
“Another stable and thus constitutively active form of Arm is ∆Arm, in which a large N-terminal region comprising the GSK3β phosphorylation and α-catenin-binding sites is replaced by a myristoylation signal (Zecca et al., 1996).”
BackgroundChai, G., Ma, C., Bao, K., Zheng, L., Wang, X., Sun, Z., Saló, E., Adell, T., & Wu, W. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.113662 · Cited by 51 · see citing works
Non-small molecule PROTACs (NSM-PROTACs): Protein degradation kaleidoscope
Ma, S., Ji, J., Tong, Y., Zhu, Y., Dou, J., Zhang, X., Xu, S., Zhu, T., Xu, X., You, Q., et al. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.02.022 · Cited by 57 · see citing works
The Roles of Intrinsic Disorder in Orchestrating the Wnt-Pathway
Xue, B., Dunker, A. K., & Uversky, V. N. (2012) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/073911012010525024 · Cited by 49 · see citing works
Swarup, S., & Verheyen, E. M. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1017548108 · Cited by 48 · see citing works
“These phosphorylation events trigger the APC-mediated extraction of β-catenin/Arm from the complex and its subsequent transfer to the Skp1-Cul1-Fbox (SCF) E3 ubiquitin ligase (9, 10).”
BackgroundHahne, G., & Grossmann, T. N. (2013) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2013.02.050 · Cited by 46 · see citing works
Signaling from the Adherens Junction
McEwen, A. E., Escobar, D. E., & Gottardi, C. J. (2012) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-94-007-4186-7_8 · Cited by 45 · see citing works
“…et al. 2001) (through binding residues in β-catenin that overlap with those that engage phospho-destruction components, APC and Axin, (Ha et al. 2004; Xing et al. 2003, 2004)), it is easy to see how cadherin cytodomain clipping could potentially liberate a substantial pool of β-catenin/cadherin…”
BackgroundHelical Repeat Structure of Apoptosis Inhibitor 5 Reveals Protein-Protein Interaction Modules
Han, B.-G., Kim, K. H., Lee, S. J., Jeong, K.-C., Cho, J., Noh, K. H., Kim, T. W., Kim, S. J., Yoon, H. J., Suh, S. W., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.317594 · Cited by 45 · see citing works
- Authors
- Xing, Y., Clements, W. K., Kimelman, D., & Xu, W.
- Affiliations
- University of Washington (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2003-01-01
- Volume
- 17
- Issue
- 22
- Pages
- 2753-2764
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC280624
- OpenAlex
- W2041827225
- Semantic Scholar
- f02d1678de9728664b949b5fed44792fbdcc704e
- Cited by
- 237
- References
- 50
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 10 · 2023: 9 · 2022: 15 · 2021: 9 · 2020: 10 · 2019: 11 · 2018: 7 · 2017: 10 · 2016: 7 · 2015: 9 · 2014: 16 · 2013: 12 · 2012: 14
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (CA 90351, R01CA090351)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD027262, HD27262)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- β-catenin, Axin, β-catenin destruction complex, Wnt/β-catenin signaling, adenomatous polyposis coli, armadillo repeats, protein-protein complex structure, β-catenin phosphorylation, protein turnover, tumor suppressor
- MeSH terms
- Amino Acid Sequence, Animals, Binding Sites, Cytoskeletal Proteins, Humans, Models, Molecular, Molecular Sequence Data, Phosphorylation, Protein Binding, Protein Conformation, Proteins, Repressor Proteins, Xenopus laevis, Signal Transduction, Trans-Activators, Sequence Homology, Amino Acid, Crystallography, X-Ray, Adenomatous Polyposis Coli Protein, Xenopus Proteins, beta Catenin, Axin Protein
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