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APP induces neuronal apoptosis through APP-BP1-mediated downregulation of β-catenin

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Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease associated with progressive dementia. This mini-review focuses on how the amyloid precursor protein (APP) plays a central role in AD and Down syndrome as the regulator of the APP-BP1/hUba3 activated neddylation pathway. It is argued that the physiological function of APP is to downregulate the level of β-catenin. However, this APP function is abnormally amplified in patients with familial AD (FAD) mutations in APP and presenilins, resulting in the hyperactivation of neddylation and the decrease of β-catenin below a threshold level. Evidence in the literature is summarized to show that dysfunction of APP in downregulating β-catenin may underlie the mechanism of neuronal death in AD and Down syndrome.

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References

  1. Glenner GG, Wong CW. Alzheimer’s disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 1984; 120(3): 885–890.

    CAS  PubMed  Google Scholar 

  2. Glenner GG, Wong CW. Alzheimer’s disease and Down’s syndrome: Sharing of a unique cerebrovascular amyloid fibril protein. Biochem Biophys Res Commun 1984; 122(3): 1131–1135.

    CAS  PubMed  Google Scholar 

  3. van Duinen SG, Castaño EM, Prelli F, Bots GT, Luyendijk W, Frangione B. Hereditary cerebral hemorrhage with amyloidosis in patients of Dutch origin is related to Alzheimer disease. Proc Natl Acad Sci USA 1987; 84(16): 5991–5994.

    CAS  PubMed  Google Scholar 

  4. Levy E, Carman MD, Fernandez-Madrid IJ, et al. Mutation of the Alzheimer’s disease amyloid gene in hereditary cerebral hemorrhage, Dutch type. Science 1990; 248(4959): 1124–1126.

    CAS  PubMed  Google Scholar 

  5. Goate A, Chartier-Harlin MC, Mullan M, et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature 1991; 349(6311): 704–706.

    CAS  PubMed  Google Scholar 

  6. Murrell J, Farlow M, Ghetti B, Benson MD. A mutation in the amyloid precursor protein associated with hereditary Alzheimer’s disease. Science 1991; 254(5028): 97–99.

    CAS  PubMed  Google Scholar 

  7. Chartier-Harlin MC, Crawford F, Houlden H, et al. Early-onset Alzheimer’s disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene. Nature 1991; 353(6347): 844–846.

    Article  CAS  PubMed  Google Scholar 

  8. Hendriks L, van Duijn CM, Cras P, et al. Presenile dementia and cerebral haemorrhage linked to a mutation at codon 692 of the beta-amyloid precursor protein gene. Nat Genet 1992; 1(3): 218–221.

    Article  CAS  PubMed  Google Scholar 

  9. Mullan M, Crawford F, Axelman K, et al. A pathogenic mutation for probable Alzheimer’s disease in the APP gene at the N-terminus of beta-amyloid. Nat Genet 1992; 1(5): 345–347.

    Article  CAS  PubMed  Google Scholar 

  10. Citron M, Oltersdorf T, Haass C, et al. Mutation of the beta-amyloid precursor protein in familial Alzheimer’s disease increases beta-protein production. Nature 1992; 360(6405): 672–674.

    Article  CAS  PubMed  Google Scholar 

  11. Suzuki N, Cheung TT, Cai XD, et al. An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta APP717) mutants. Science 1994; 264(5163): 1336–1340.

    CAS  PubMed  Google Scholar 

  12. Goate A, Chartier-Harlin MC, Mullan M, et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature 1991; 349(6311): 704–706.

    CAS  PubMed  Google Scholar 

  13. Mattson MP. Apoptosis in neurodegenerative disorders. Nautre Rev Mol Cell Biol 2000; 1: 120–129.

    Article  CAS  Google Scholar 

  14. Arendt T. Dysregulation of neuronal differentiation and cell cycle control in Alzheimer’s disease. J Neural Transm Suppl 2002; (62): 77–85.

    CAS  PubMed  Google Scholar 

  15. Keller JN, Keith BH, Markesbery WR. Impaired proteasome function in Alzheimer’s disease. J Neurochem 2000; 75(1): 436–439.

    CAS  PubMed  Google Scholar 

  16. Keller JN, Hanni KB, Markesbery WR. Possible involvement of proteasome inhibition in aging: Implications for oxidative stress. Mechanisms of Aging and Dev 2000; 113: 61–70.

    CAS  Google Scholar 

  17. van Leeuwen FW, de Kleijn DP, van den Hurk HH, et al. Frameshift mutants of beta amyloid precursor protein and ubiquitin-B in Alzheimer’s and Down patients. Science 1998; 279(5348): 242–247.

    CAS  PubMed  Google Scholar 

  18. Lam YA, Pickart CM, Alban A, et al. Inhibition of the ubiquitin-proteasome system in Alzheimer’s disease. Proc Natl Acad Sci USA 2000; 97(18): 9902–9906.

    CAS  PubMed  Google Scholar 

  19. Chow N, Korenberg JR, Chen XN, Neve RL. APP-BP1, a novel protein that binds to the carboxyl-terminal region of the amyloid precursor protein. J Biol Chem 1996; 271(19): 11339–11346.

    CAS  PubMed  Google Scholar 

  20. Chen Y, McPhie DL, Hirschberg J, Neve RL. The amyloid precursor protein-binding protein APP-BP1 drives the cell cycle through the S-M checkpoint and causes apoptosis in neurons.J Biol Chem 2000; 275(12): 8929–8935.

    CAS  PubMed  Google Scholar 

  21. Osaka F, Kawasaki H, Aida N, et al. A new NEDD8-ligating system for cullin-4A. Genes Dev 1998; 12(15): 2263–2268.

    CAS  PubMed  Google Scholar 

  22. Gong L, Yeh ET. Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway. J Biol Chem 1999; 274(17): 12036–12042.

    CAS  PubMed  Google Scholar 

  23. Hori T, Osaka F, Chiba T, et al. Covalent modification of all members of human cullin family proteins by NEDD8. Oncogene 1999; 18(48): 6829–6834.

    CAS  PubMed  Google Scholar 

  24. Hirschberg J, Marcus M. Isolation of temperature-sensitive mutants.Methods Enzymol 1987; 151: 145–150.

    CAS  PubMed  Google Scholar 

  25. Handeli S, Weintraub H. The ts41 mutation in Chinese hamster cells leads to successive S phases in the absence of intervening G2, M, and G1. Cell 1992; 71(4): 599–611.

    CAS  PubMed  Google Scholar 

  26. Tateishi K, Omata M, Tanaka K, Chiba T. The NEDD8 system is essential for cell cycle progression and morphogenetic pathway in mice. J Cell Biol 2001; 155(4): 571–579.

    CAS  PubMed  Google Scholar 

  27. Chen Y, Liu W, McPhie DL, Hassinger L, Neve RL. APP-BP1 mediates APP-induced apoptosis and DNA synthesis and is increased in Alzheimer’s disease brain. J Cell Biol 2003; 163(1): 27–33.

    CAS  PubMed  Google Scholar 

  28. Chen Y, Liu W, Naumovski L, Neve RL. ASPP2 inhibits APP-BP1-mediated NEDD8 conjugation to cullin-1 and decreases APP-BP1-induced cell proliferation and neuronal apoptosis. J Neurochem 2003; 85(3): 801–809.

    CAS  PubMed  Google Scholar 

  29. Deshaies RJ. SCF and Cullin/Ring H2-based ubiquitin ligases. Annu Rev Cell Dev Biol 1999; 15: 435–467.

    Article  CAS  PubMed  Google Scholar 

  30. del Pozo JC, Estelle M. F-box proteins and protein degradation: An emerging theme in cellular regulation. Plant Mol Biol 2000; 44(2): 123–128.

    CAS  PubMed  Google Scholar 

  31. Kipreos ET, Lander LE, Wing JP, He WW, Hedgecock EM. cul-1 is required for cell cycle exit in C. elegans and identifies a novel gene family. Cell 1996; 85(6): 829–839.

    CAS  PubMed  Google Scholar 

  32. Kaelin WG Jr. Molecular basis of the VHL hereditary cancer syndrome. Nat Rev Cancer 2002; 2(9): 673–682.

    Article  CAS  PubMed  Google Scholar 

  33. Pintard L, Kurz T, Glaser S, Willis JH, Peter M, Bowerman B. Neddylation and deneddylation of CUL-3 is required to target MEI-1/Katanin for degradation at the meiosis-to-mitosis transition in C. elegans. Curr Biol 2003; 13(11): 911–921.

    CAS  PubMed  Google Scholar 

  34. Zhong W, Feng H, Santiago FE, Kipreos ET. CUL-4 ubiquitin ligase maintains genome stability by restraining DNA-replication licensing. Nature 2003; 423(6942): 885–889.

    CAS  PubMed  Google Scholar 

  35. Kang J, Lemaire HG, Unterbeck A, et al. The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor. Nature 1987; 325(6106): 733–736.

    CAS  PubMed  Google Scholar 

  36. Storey E, Spurck T, Pickett-Heaps J, Beyreuther K, Masters CL. The amyloid precursor protein of Alzheimer’s disease is found on the surface of static but not activity motile portions of neurites. Brain Res 1996; 735(1): 59–66.

    CAS  PubMed  Google Scholar 

  37. Jung SS, Nalbantoglu J, Cashman NR. Alzheimer’s beta-amyloid precursor protein is expressed on the surface of immediately ex vivo brain cells: A flow cytometric study. J Neurosci Res 1996; 46(3): 336–348.

    CAS  PubMed  Google Scholar 

  38. Qiu WQ, Ferreira A, Miller C, Koo EH, Selkoe DJ. Cell-surface ?-amyloid precursor protein stimulates neurite outgrowth of hippocampal neurons in an isoform-dependent manner. J Neurosci 1995; 15: 2157–2167.

    CAS  PubMed  Google Scholar 

  39. Marquez-Sterling NR, Lo AC, Sisodia SS, Koo EH. Trafficking of cell-surface beta-amyloid precursor protein: Evidence that a sorting intermediate participates in synaptic vesicle recycling. J Neurosci 1997; 17(1): 140–151.

    CAS  PubMed  Google Scholar 

  40. Koo EH, Squazzo SL, Selkoe DJ, Koo CH. Trafficking of cell-surface amyloid beta-protein precursor. I. Secretion, endocytosis and recycling as detected by labeled monoclonal antibody. J Cell Sci 1996; 109(Pt 5): 991–998.

    CAS  PubMed  Google Scholar 

  41. Yamazaki T, Koo EH, Selkoe DJ. Trafficking of cell-surface amyloid beta-protein precursor. II. Endocytosis, recycling and lysosomal targeting detected by immunolocalization. J Cell Sci 1996; 109(Pt 5): 999–1008.

    CAS  PubMed  Google Scholar 

  42. Small DH, Nurcombe V, Reed G, et al. A heparin-binding domain in the amyloid protein precursor of Alzheimer’s disease is involved in the regulation of neurite outgrowth. J Neurosci 1994; 14(4): 2117–2127.

    CAS  PubMed  Google Scholar 

  43. Kibbey MC, Jucker M, Weeks BS, Neve RL, Van Nostrand WE, Kleinman HK. beta-Amyloid precursor protein binds to the neurite-promoting IKVAV site of laminin. Proc Natl Acad Sci USA 1993; 90(21): 10150–10153.

    CAS  PubMed  Google Scholar 

  44. Beher D, Hesse L, Masters CL, Multhaup G. Regulation of amyloid protein precursor (APP) binding to collagen and mapping of the binding sites on APP and collagen type I. J Biol Chem 1996; 271(3): 1613–1620.

    CAS  PubMed  Google Scholar 

  45. Caceres J, Brandan E. Interaction between Alzheimer’s disease beta A4 precursor protein (APP) and the extracellular matrix: Evidence for the participation of heparan sulfate proteoglycans. J Cell Biochem 1997; 65(2): 145–158.

    CAS  PubMed  Google Scholar 

  46. Miyazaki K, Hasegawa M, Funahashi K, Umeda M. A metalloproteinase inhibitor domain in Alzheimer amyloid protein precursor. Nature 1993; 362(6423): 839–841.

    CAS  PubMed  Google Scholar 

  47. Higashi S, Miyazaki K. Novel processing of beta-amyloid precursor protein catalyzed by membrane type 1 matrix metalloproteinase releases a fragment lacking the inhibitor domain against gelatinase A. Biochemistry 2003; 42(21): 6514–6526.

    CAS  PubMed  Google Scholar 

  48. Scheuermann S, Hambsch B, Hesse L, et al. Homodimerization of amyloid precursor protein and its implication in the amyloidogenic pathway of Alzheimer’s disease. J Biol Chem 2001; 276(36): 33923–33929.

    CAS  PubMed  Google Scholar 

  49. Nishimoto I, Okamoto T, Matsuura Y, Okamoto T, Murayama Y, Ogata E. Alzheimer amyloid protein precursor complexes with brain GTP-binding protein G(o). Nature 1993; 362: 75–79.

    CAS  PubMed  Google Scholar 

  50. Russo T, Faraonio R, Minopoli G, De Candia P, De Renzis S, Zambrano N. Fe65 and the protein network centered around the cytosolic domain of the Alzheimer’s ?-amyloid precursor protein. FEBS Lett 1998; 434: 1–7.

    CAS  PubMed  Google Scholar 

  51. Watanabe T, Sukegawa J, Sukegawa I, et al. A 127-kDa protein (UV-DDB) binds to the cytoplasmic domain of the Alzheimer’s amyloid precursor protein. J Neurochem 1999; 72: 549–556.

    CAS  PubMed  Google Scholar 

  52. Cao X, Sudhof TC. A transcriptionally [correction of transcriptively] active complex of APP with Fe65 and histone acetyltransferase Tip60. Science 2001; 293(5527): 115–120.

    CAS  PubMed  Google Scholar 

  53. Scheinfeld MH, Roncarati R, Vito P, Lopez PA, Abdallah M, D’Adamio L. Jun NH2-terminal kinase (JNK) interacting protein 1 (JIP1) binds the cytoplasmic domain of the Alzheimer’s beta-amyloid precursor protein (APP). J Biol Chem 2002; 277(5): 3767–3775.

    CAS  PubMed  Google Scholar 

  54. Zheng H, Jiang M, Trumbauer ME, et al. beta-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity. Cell 1995; 81(4): 525–531.

    CAS  PubMed  Google Scholar 

  55. Suzuki T, Oishi M, Marshak DR, Czernik AJ, Nairn AC, Greengard P. Cell cycle-dependent regulation of the phosphorylation and metabolism of the Alzheimer amyloid precursor protein. EMBO J 1994; 13(5): 1114–1122.

    CAS  PubMed  Google Scholar 

  56. Suzuki T, Ando K, Isohara T, et al. Phosphorylation of Alzheimer beta-amyloid precursor-like proteins. Biochemistry 1997; 36(15): 4643–4649.

    CAS  PubMed  Google Scholar 

  57. Nishimura I, Uetsuki T, Dani SU, et al. Degeneration in vivo of rat hippocampal neurons by wild-type Alzheimer amyloid precursor protein overexpressed by adenovirus-mediated gene transfer. J Neurosci 1998; 18(7): 2387–2398.

    CAS  PubMed  Google Scholar 

  58. Rohn TT, Ivins KJ, Bahr BA, Cotman CW, Cribbs DH. Amonoclonal antibody to amyloid precursor protein induces neuronal apoptosis. J Neurochem 2000; 74(6): 2331–2342.

    CAS  PubMed  Google Scholar 

  59. Wisniewski KE, Wisniewski HM, Wen GY. Occurrence of neuropathological changes and dementia of Alzheimer’s disease in Down’s syndrome. Ann Neurol 1985; 17(3): 278–282.

    CAS  PubMed  Google Scholar 

  60. Bouillot C, Prochiantz A, Rougon G, Allinquant B. Axonal amyloid precursor protein expressed by neurons in vitro is present in a membrane fraction with caveolae-like properties. J Biol Chem 1996; 271(13): 7640–7644.

    CAS  PubMed  Google Scholar 

  61. Riddell DR, Christie G, Hussain I, Dingwall C. Compartmentalization of beta-secretase (Asp2) into low-buoyant density, noncaveolar lipid rafts. Curr Biol 2001; 11(16): 1288–1293.

    CAS  PubMed  Google Scholar 

  62. Lee SJ, Liyanage U, Bickel PE, Xia W, Lansbury PT Jr, Kosik KS. A detergent-insoluble membrane compartment contains A beta in vivo. Nat Med 1998; 4(6): 730–4.

    CAS  PubMed  Google Scholar 

  63. Simons M, Keller P, De Strooper B, Beyreuther K, Dotti CG, Simons K. Cholesterol depletion inhibits the generation of beta-amyloid in hippocampal neurons. Proc Natl Acad Sci USA 1998; 95(11): 6460–6464.

    CAS  PubMed  Google Scholar 

  64. Tun H, Marlow L, Pinnix I, Kinsey R, Sambamurti K. Lipid rafts play an important role in A beta biogenesis by regulating the beta-secretase pathway. J Mol Neurosci 2002; 19(1/2): 31–35.

    CAS  PubMed  Google Scholar 

  65. Ehehalt R, Keller P, Haass C, Thiele C, Simons K. Amyloidogenic processing of the Alzheimer beta-amyloid precursor protein depends on lipid rafts. J Cell Biol 2003; 160(1): 113–123.

    CAS  PubMed  Google Scholar 

  66. Read MA, Brownell JE, Gladysheva TB, et al. Nedd8 modification of cul-1 activates SCF(beta(TrCP))-dependent ubiquitination of IkappaBalpha. Mol Cell Biol 2000; 20(7): 2326–2333.

    CAS  PubMed  Google Scholar 

  67. Ohh M, Kim WY, Moslehi JJ, et al. An intact NEDD8 pathway is required for Cullin-dependent ubiquitylation in mammalian cells. EMBO Rep 2002; 3(2): 177–182.

    CAS  PubMed  Google Scholar 

  68. Bruni P, Minopoli G, Brancaccio T, et al. Fe65, a ligand of the Alzheimer’s beta-amyloid precursor protein, blocks cell cycle progression by down-regulating thymidylate synthase expression. J Biol Chem 2002; 277(38): 35481–35488.

    CAS  PubMed  Google Scholar 

  69. Rassoulzadegan M, Yang Y, Cuzin F. APLP2, a member of the Alzheimer precursor protein family, is required for correct genomic segregation in dividing mouse cells. EMBO J 1998; 17(16): 4647–4656.

    CAS  PubMed  Google Scholar 

  70. Esler WP, Wolfe MS. A portrait of Alzheimer secretases-Newfeatures and familiar faces. Science 2001; 293(5534): 1449–1454.

    CAS  PubMed  Google Scholar 

  71. Ho A, Sudhof TC. Binding of F-spondin to amyloid-beta precursor protein: A candidate amyloid-beta precursor protein ligand that modulates amyloid-beta precursor protein cleavage. Proc Natl Acad Sci USA 2004; 101(8): 2548–2553.

    CAS  PubMed  Google Scholar 

  72. Murayama M, Tanaka S, Palacino J, et al. Direct association of presenilin-1 with beta-catenin. FEBS Lett 1998; 433(1/2): 73–77.

    CAS  PubMed  Google Scholar 

  73. Yu G, Chen F, Levesque G, et al. The presenilin 1 protein is a component of a high molecular weight intracellular complex that contains beta-catenin. J Biol Chem 1998; 273(26): 16470–16475.

    CAS  PubMed  Google Scholar 

  74. Nelson WJ, Nusse R. Convergence of Wnt, ?-catenin, and cadherin pathways. Science 2004; 303: 1483–1487.

    CAS  PubMed  Google Scholar 

  75. Zhang Z, Hartmann H, Do VM, et al. Destabilization of beta-catenin by mutations in presenilin-1 potentiates neuronal apoptosis. Nature 1998; 395(6703): 698–702.

    CAS  PubMed  Google Scholar 

  76. Xia X, Qian S, Soriano S, et al. Loss of presenilin 1 is associated with enhanced beta-catenin signaling and skin tumorigenesis. Proc Natl Acad Sci USA 2001; 98(19): 10863–10868.

    CAS  PubMed  Google Scholar 

  77. Marambaud P, Wen PH, Dutt A, et al. A CBP binding transcriptional repressor produced by the PS1/epsilon-cleavage of N-cadherin is inhibited by PS1 FAD mutations. Cell 2003; 114(5): 635–645.

    CAS  PubMed  Google Scholar 

  78. Killick R, Pollard CC, Asuni AA, et al. Presenilin 1 independently regulates ?-catenin stability and transcriptional activity. J Biol Chem 2001; 276(51): 48554–48561.

    CAS  PubMed  Google Scholar 

  79. Kang DE, Soriano S, Xia X, et al. Presenilin couples the paired phosphorylation of beta-catenin independent of axin: Implications for beta-catenin activation in tumorigenesis. Cell 2002; 110(6): 751–762.

    CAS  PubMed  Google Scholar 

  80. Heyn SN, Vulliet PR. Presenilin 1 mutations increase amyloid precursor protein production and proteolysis in Xenopus laevis oocytes. Brain Res 2001; 904(2): 189–198.

    CAS  PubMed  Google Scholar 

  81. van Broeckhoven C, Haan J, Bakker E, et al. Amyloid beta protein precursor gene and hereditary cerebral hemorrhage with amyloidosis (Dutch). Science 1990; 248(4959): 1120–1122.

    CAS  PubMed  Google Scholar 

  82. Grabowski TJ, Cho HS, Vonsattel JP, Rebeck GW, Greenberg SM. Novel amyloid precursor protein mutation in an Iowa family with dementia and severe cerebral amyloid angiopathy. Ann Neurol 2001; 49(6): 697–705.

    CAS  PubMed  Google Scholar 

  83. Weihl CC, Miller RJ, Roos RP. The role of beta-catenin stability in mutant PS1-associated apoptosis. Neuroreport 1999; 10(12): 2527–2532.

    CAS  PubMed  Google Scholar 

  84. Ertekin-Taner N, Ronald J, Asahara H, et al. Fine mapping of the alpha-T catenin gene to a quantitative trait locus on chromosome 10 in late-onset Alzheimer’s disease pedigrees. Hum Mol Genet 2003; 12(23): 3133–3143.

    CAS  PubMed  Google Scholar 

  85. Vasioukhin V, Bauer C, Degenstein L, Wise B, Fuchs E. Hyperproliferation and defects in epithelial polarity upon conditional ablation of alpha-catenin in skin. Cell 2001; 104(4): 605–617.

    CAS  PubMed  Google Scholar 

  86. Giles RH, van Es JH, Clevers H. Caught up in a Wnt storm: Wnt signaling in cancer. Biochim Biophys Acta 2003; 1653(1): 1–24.

    CAS  PubMed  Google Scholar 

  87. Chenn A, Walsh CA. Regulation of cerebral cortical size by control of cell cycle exit in neural precursors. Science 2002; 297(5580): 365–369.

    CAS  PubMed  Google Scholar 

  88. Kirazov E, Kirazov L, Bigl V, Schliebs R. Ontogenetic changes in protein level of amyloid precursor protein (APP) in growth cones and synaptosomes from rat brain and prenatal expression pattern of APP mRNA isoforms in developing rat embryo. Int J Dev Neurosci 2001; 19(3): 287–296.

    CAS  PubMed  Google Scholar 

  89. Okano H. Stem cell biology of the central nervous system. J Neurosci Res 2002; 69: 698–707.

    CAS  PubMed  Google Scholar 

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  1. Department of Geriatrics, College of Medicine, University of Arkansas for Medical Sciences, AR, 72205, USA

    Y. Z. Chen

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Chen, Y.Z. APP induces neuronal apoptosis through APP-BP1-mediated downregulation of β-catenin. Apoptosis 9, 415–422 (2004). https://doi.org/10.1023/B:APPT.0000031447.05354.9f

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