Wnt signaling: Is the party in the nucleus?

Genes and Development

Volumn 20, Issue 11, 2006, Pages 1394-1404

  Willert, Karl ^a   Jones, Katherine A ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b SALK INSTITUTE FOR BIOLOGICAL STUDIES   (United States)

Author keywords

catenin; APC; CtBP; Cyclic transcription; Histone methylation; Wnt signaling

Indexed keywords

ACTIN; APC PROTEIN; AXIN; BETA CATENIN; DNA; HISTONE METHYLTRANSFERASE; UVOMORULIN; WNT PROTEIN;

CANCER; CELL NUCLEUS; CELL PROLIFERATION; GENE EXPRESSION; GENE TARGETING; METHYLATION; POLYMERIZATION; PRIORITY JOURNAL; REVIEW; TRANSACTIVATION;

ANIMALS; BETA CATENIN; CELL NUCLEUS; GENES, APC; NEOPLASMS; SIGNAL TRANSDUCTION; STEM CELLS; WNT PROTEINS;

EID: 33744791463     PISSN: 08909369     EISSN: 15495477     Source Type: Journal    
DOI: 10.1101/gad.1424006     Document Type: Review

References (104)

1. Adelman, K., Wei, W., Ardehali, M.B., Werner, J., Zhu, B., Reinberg, D., and Lis, J.T. 2006. Drosophila Paf1 modulates chromatin structure at actively transcribed genes. Mol. Cell. Biol. 26: 250-260.
2. Ahumada, A., Slusarski, D.C., Liu, X., Moon, R.T., Malbon, C.C., and Wang, H.Y. 2002. Signaling of rat Frizzled-2 through phosphodiesterase and cyclic GMP. Science 298: 2006-2010.
3. Aulehla, A. and Herrmann, B.G. 2004. Segmentation in vertebrates: Clock and gradient finally joined. Genes & Dev. 18: 2060-2067.
4. Aulehla, A., Wehrle, C., Brand-Saberi, B., Kemler, R., Gossler, A., Kanzler, B., and Herrmann, B.G. 2003. Wnt3a plays a major role in the segmentation clock controlling somitogenesis. Dev. Cell 4: 395-406.
5. Barker, N., Hurlstone, A., Musisi, H., Miles, A., Bienz, M., and Clevers, H. 2001. The chromatin remodeling factor Brg-1 interacts with β-catenin to promote target gene activation. EMBO J. 20: 4935-4943.
6. Bauer, A., Chauvet, S., Huber, O., Usseglio, F., Rothbacher, U., Aragnol, D., Kemler, R., and Pradel, J. 2000. Pontin52 and reptin52 function as antagonistic regulators of β-catenin signalling activity. EMBO J. 19: 6121-6130.
7. Belenkaya, T.Y., Han, C., Standley, H.J., Lin, X., Houston, D.W., Heasman, J., and Lin, X. 2002. pygopus Encodes a nuclear protein essential for wingless/Wnt signaling. Development 129: 4089-4101.
8. Bienz, M. 2002. The subcellular destinations of APC proteins. Nat. Rev. Mol. Cell Biol. 3: 328-338.
9. _. 2005. β-Catenin: A pivot between cell adhesion and Wnt signalling. Curr. Biol. 15: R64-R67.
10. Bienz, M. and Clevers, H. 2003. Armadillo/β-catenin signals in the nucleus-Proof beyond a reasonable doubt? Nat. Cell Biol. 5: 179-182.
11. Bienz, M. and Hamada, F. 2004. Adenomatous polyposis coli proteins and cell adhesion. Curr. Opin. Cell Biol. 16: 528-535.
12. Blessing, C.A., Ugrinova, G.T., and Goodson, H.V. 2004. Actin and ARPs: Action in the nucleus. Trends Cell Biol. 14: 435-442.
13. Brembeck, F.H., Schwarz-Romond, T., Bakkers, J., Wilhelm, S., Hammerschmidt, M., and Birchmeier, W. 2004. Essential role of BCL9-2 in the switch between β-catenin's adhesive and transcriptional functions. Genes & Dev. 18: 2225-2230.
14. Cadigan, K.M. 2002. Wnt signaling - 20 years and counting. Trends Genet. 18: 340-342.
15. Cao, R. and Zhang, Y. 2004. The functions of E(Z)/EZH2-mediated methylation of lysine 27 in histone H3. Curr. Opin. Genet. Dev. 14: 155-164.
16. Castellone, M.D., Teramoto, H., Williams, B.O., Druey, K.M., and Gutkind, J.S. 2005. Prostaglandin E2 promotes colon cancer cell growth through a Gs-axin-β-catenin signaling axis. Science 310: 1504-1510.
17. Cha, T.L., Zhou, B.P., Xia, W., Wu, Y., Yang, C.C., Chen, C.T., Ping, B., Otte, A.P., and Hung, M.C. 2005. Akt-mediated phosphorylation of EZH2 suppresses methylation of lysine 27 in histone H3. Science 310: 306-310.
18. Chen, J., Wu, A., Sun, H., Drakas, R., Garofalo, C., Cascio, S., Surmacz, E., and Baserga, R. 2005. Functional significance of type 1 insulin-like growth factor-mediated nuclear translocation of the insulin receptor substrate-1 and β-catenin. J. Biol. Chem. 280: 29912-29920.
19. Chinnadurai, G. 2002. CtBP, an unconventional transcriptional corepressor in development and oncogenesis. Mol. Cell 9: 213-224.
20. Choi, C.Y., Kim, Y.H., Kim, Y.O., Park, S.J., Kim, E.A., Riemenschneider, W., Gajewski, K., Schulz, R.A., and Kim, Y. 2005. Phosphorylation by the dHIPK2 protein kinase modulates the corepressor activity of Groucho. J. Biol. Chem. 280: 21427-21436.
21. Collins, R.T. and Treisman, J.E. 2000. Osa-containing Brahma chromatin remodeling complexes are required for the repression of wingless target genes. Genes & Dev. 14: 3140-3152.
22. Conacci-Sorrell, M., Simcha, I., Ben-Yedidia, T., Blechman, J., Savagner, P., and Ben-Ze'ev, A. 2003. Autoregulation of Ecadherin expression by cadherin-cadherin interactions: The roles of β-catenin signaling, Slug, and MAPK. J. Cell Biol. 163: 847-857.
23. Cong, F. and Varmus, H. 2004. Nuclear-cytoplasmic shuttling of Axin regulates subcellular localization of β-catenin. Proc. Natl. Acad. Sci. 101: 2882-2887.
24. Dale, J.K., Malapert, P., Chal, J., Vilhais-Neto, G., Maroto, M., Johnson, T., Jayasinghe, S., Trainor, P., Herrmann, B., and Pourquie, O. 2006. Oscillations of the snail genes in the presomitic mesoderm coordinate segmental patterning and morphogenesis in vertebrate somitogenesis. Dev. Cell 10: 355-366.
25. Daniels, D.L. and Weis, W.I. 2005. β-catenin directly displaces Groucho/TLE repressors from Tcf/Lef in Wnt-mediated transcription activation. Nat. Struct. Mol. Biol. 12: 364-371.
26. DasGupta, R., Kaykas, A., Moon, R.T., and Perrimon, N. 2005. Functional genomic analysis of the Wnt-wingless signaling pathway. Science 308: 826-833.
27. Davidson, G., Wu, W., Shen, J., Bilic, J., Fenger, U., Stannek, P., Glinka, A., and Niehrs, C. 2005. Casein kinase 1 γ couples Wnt receptor activation to cytoplasmic signal transduction. Nature 438: 867-872.
28. Ding, Q., Xia, W., Liu, J.C., Yang, J.Y., Lee, D.F., Xia, J., Bartholomeusz, G., Li, Y., Pan, Y., Li, Z., et al. 2005. Erk associates with and primes GSK-3β for its inactivation resulting in upregulation of β-catenin. Mol. Cell 19: 159-170.
29. Dou, Y., Milne, T.A., Tackett, A.J., Smith, E.R., Fukuda, A., Wysocka, J., Allis, C.D., Chait, B.T., Hess, J.L., and Roeder, R.G. 2005. Physical association and coordinate function of the H3 K4 methyltransferase MLL1 and the H4 K16 acetyltransferase MOF. Cell 121: 873-885.
30. Dravid, G., Ye, Z., Hammond, H., Chen, G., Pyle, A., Donovan, P., Yu, X., and Cheng, L. 2005. Defining the role of Wnt/β-catenin signaling in the survival, proliferation, and self-renewal of human embryonic stem cells. Stem Cells 23: 1489-1501.
31. Drees, F., Pokutta, S., Yamada, S., Nelson, W.J., and Weis, W.I. 2005. α-Catenin is a molecular switch that binds E-cadherin -β-catenin and regulates actin-filament assembly. Cell 123: 903-915.
32. Dubrulle, J. and Pourquie, O. 2004. Coupling segmentation to axis formation. Development 131: 5783-5793.
33. Ezhkova, E. and Tansey, W.P. 2004. Proteasomal ATPases link ubiquitylation of histone H2B to methylation of histone H3. Mol. Cell 13: 435-442.
34. Galceran, J., Sustmann, C., Hsu, S.C., Folberth, S., and Grosschedl, R. 2004. LEF1-mediated regulation of Delta-like1 links Wnt and Notch signaling in somitogenesis. Genes & Dev. 18: 2718-2723.
35. Giannini, A.L., Vivanco, M., and Kypta, R.M. 2000. α-Catenin inhibits β-catenin signaling by preventing formation of a β-catenin*T-cell factor*DNA complex. J. Biol. Chem. 275: 21883-21888.
36. Gottardi, C.J. and Gumbiner, B.M. 2004. Distinct molecular forms of α-catenin are targeted to adhesive or transcriptional complexes. J. Cell Biol. 167: 339-349.
37. Gregorieff, A. and Clevers, H. 2005. Wnt signaling in the intestinal epithelium: From endoderm to cancer. Genes & Dev. 19: 877-890.
38. Ha, N.C., Tonozuka, T., Stamos, J.L., Choi, H.J., and Weis, W.I. 2004. Mechanism of phosphorylation-dependent binding of APC to β-catenin and its role in β-catenin degradation. Mol. Cell 15: 511-521.
39. Habas, R. and Dawid, I.B. 2005. Dishevelled and Wnt signaling: Is the nucleus the final frontier? J. Biol. 4: 2.
40. Hamada, F. and Bienz, M. 2004. The APC tumor suppressor binds to C-terminal binding protein to divert nuclear β-catenin from TCF. Dev. Cell 7: 677-685.
41. Hammerlein, A., Weiske, J., and Huber, O. 2005. A second protein kinase CK1-mediated step negatively regulates Wnt signalling by disrupting the lymphocyte enhancer factor-1/β-catenin complex. Cell. Mol. Life Sci. 62: 606-618.
42. Harris, T.J. and Peifer, M. 2005. Decisions, decisions: β-Catenin chooses between adhesion and transcription. Trends Cell Biol. 15: 234-237.
43. Hoffmans, R., Stadeli, R., and Basler, K. 2005. Pygopus and legless provide essential transcriptional coactivator functions to armadillo/β- catenin. Curr. Biol. 15: 1207-1211.
44. Hofmann, M., Schuster-Gossler, K., Watabe-Rudolph, M., Aulehla, A., Herrmann, B.G., and Gossler, A. 2004. WNT signaling, in synergy with T/TBX6, controls Notch signaling by regulating Dll1 expression in the presomitic mesoderm of mouse embryos. Genes & Dev. 18: 2712-2717.
45. Huber, M.A., Kraut, N., and Beug, H. 2005. Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr. Opin. Cell Biol. 17: 548-558.
46. Jonsson, Z.O., Jha, S., Wohlschlegel, J.A., and Dutta, A. 2004. Rvb1p/Rvb2p recruit Arp5p and assemble a functional Ino80 chromatin remodeling complex. Mol. Cell 16: 465-477.
47. Kadrmas, J.L. and Beckerle, M.C. 2004. The LIM domain: From the cytoskeleton to the nucleus. Nat. Rev. Mol. Cell Biol. 5: 920-931.
48. Katanaev, V.L., Ponzielli, R., Semeriva, M., and Tomlinson, A. 2005. Trimeric G protein-dependent frizzled signaling in Drosophila. Cell 120: 111-122.
49. Kawamura, A., Koshida, S., Hijikata, H., Ohbayashi, A., Kondoh, H., and Takada, S. 2005. Groucho-associated transcriptional repressor ripply1 is required for proper transition from the presomitic mesoderm to somites. Dev. Cell 9: 735-744.
50. Kinzler, K.W. and Vogelstein, B. 1996. Lessons from hereditary colorectal cancer. Cell 87: 159-170.
51. Kohn, A.D. and Moon, R.T. 2005. Wnt and calcium signaling: β-Catenin-independent pathways. Cell Calcium 38: 439-446.
52. Kramps, T., Peter, O., Brunner, E., Nellen, D., Froesch, B., Chatterjee, S., Murone, M., Zullig, S., and Basler, K. 2002. Wnt/wingless signaling requires BCL9/legless-mediated recruitment of pygopus to the nuclear β-catenin-TCF complex. Cell 109: 47-60.
53. Kuhnert, F., Davis, C.R., Wang, H.T., Chu, P., Lee, M., Yuan, J., Nusse, R., and Kuo, C.J. 2004. Essential requirement for Wnt signaling in proliferation of adult small intestine and colon revealed by adenoviral expression of Dickkopf-1. Proc. Natl. Acad. Sci. 101: 266-271.
54. Lee, E., Salic, A., Kruger, R., Heinrich, R., and Kirschner, M.W. 2003. The roles of APC and Axin derived from experimental and theoretical analysis of the Wnt pathway. PLoS Biol. 1: E10.
55. Liu, B.Y., McDermott, S.P., Khwaja, S.S., and Alexander, C.M. 2004. The transforming activity of Wnt effectors correlates with their ability to induce the accumulation of mammary progenitor cells. Proc. Natl. Acad. Sci. 101: 4158-4163.
56. Liu, X., Rubin, J.S., and Kimmel, A.R. 2005. Rapid, Wnt-induced changes in GSK3β associations that regulate β-catenin stabilization are mediated by Gβ proteins. Curr. Biol. 15: 1989-1997.
57. Lowry, W.E., Blanpain, C., Nowak, J.A., Guasch, G., Lewis, L., and Fuchs, E. 2005. Defining the impact of β-catenin/Tcf transactivation on epithelial stem cells. Genes & Dev. 19: 1596-1611.
58. Merrill, B.J., Gat, U., DasGupta, R., and Fuchs, E. 2001. Tcf3 and Lef1 regulate lineage differentiation of multipotent stem cells in skin. Genes & Dev. 15: 1688-1705.
59. Moon, R.T., Kohn, A.D., De Ferrari, G.V., and Kaykas, A. 2004. WNT and β-catenin signalling: Diseases and therapies. Nat. Rev. Genet. 5: 691-701.
60. Morales, A.V., Yasuda, Y., and Ish-Horowicz, D. 2002. Periodic Lunatic fringe expression is controlled during segmentation by a cyclic transcriptional enhancer responsive to notch signaling. Dev. Cell 3: 63-74.
61. Mosimann, C., Hausmann, G., and Basler, K. 2006. Parafibromin/Hyrax activates Wnt/Wg target gene transcription by direct association with β-catenin/Armadillo. Cell 125: 327-341.
62. Nelson, W.J. and Nusse, R. 2004. Convergence of Wnt, β-catenin, and cadherin pathways. Science 303: 1483-1487.
63. Nolz, J.C., Gomez, T.S., and Billadeau, D.D. 2005. The Ezh2 methyltransferase complex: Actin up in the cytosol. Trends Cell Biol. 15: 514-517.
64. Nusse, R., van Ooyen, A., Cox, D., Fung, Y.K., and Varmus, H. 1984. Mode of proviral activation of a putative mammary oncogene (int-1) on mouse chromosome 15. Nature 307: 131-136.
65. Olave, I.A., Reck-Peterson, S.L., and Crabtree, G.R. 2002. Nuclear actin and actin-related proteins in chromatin remodeling. Annu. Rev. Biochem. 71: 755-781.
66. Parker, D.S., Jemison, J., and Cadigan, K.M. 2002. Pygopus, a nuclear PHD-finger protein required for Wingless signaling in Drosophila. Development 129: 2565-2576.
67. Perissi, V. and Rosenfeld, M.G. 2005. Controlling nuclear receptors: The circular logic of cofactor cycles. Nat. Rev. Mol. Cell Biol. 6: 542-554.
68. Pinto, D., Gregorieff, A., Begthel, H., and Clevers, H. 2003. Canonical Wnt signals are essential for homeostasis of the intestinal epithelium. Genes & Dev. 17: 1709-1713.
69. Price, M.A. 2006. CKI, there's more than one: Casein kinase I family members in Wnt and Hedgehog signaling. Genes & Dev. 20: 399-410.
70. Radtke, F. and Clevers, H. 2005. Self-renewal and cancer of the gut: Two sides of a coin. Science 307: 1904-1909.
71. Reya, T. and Clevers, H. 2005. Wnt signalling in stem cells and cancer. Nature 434: 843-850.
72. Reya, T., Duncan, A.W., Ailles, L., Domen, J., Scherer, D.C., Willert, K., Hintz, L., Nusse, R., and Weissman, I.L. 2003. A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature 423: 409-414.
73. Sato, N., Meijer, L., Skaltsounis, L., Greengard, P., and Brivanlou, A.H. 2004. Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor. Nat. Med. 10: 55-63.
74. Shackleton, M., Vaillant, F., Simpson, K.J., Stingl, J., Smyth, G.K., Asselin-Labat, M.L., Wu, L., Lindeman, G.J., and Visvader, J.E. 2006. Generation of a functional mammary gland from a single stem cell. Nature 439: 84-88.
75. Shi, Y., Sawada, J., Sui, G., Affar el, B., Whetstine, J.R., Lan, F., Ogawa, H., Luke, M.P., Nakatani, Y., and Shi, Y. 2003. Coordinated histone modifications mediated by a CtBP co-repressor complex. Nature 422: 735-738.
76. Sierra, J., Yoshida, T., Joazeiro, C., and Jones, K.A. 2006. The APC tumor suppressor counteracts β-catenin activation and H3K4 methylation at Wnt target genes. Genes & Dev. 20: 586-600.
77. Sims III, R.J., Mandal, S.S., and Reinberg, D. 2004. Recent highlights of RNA polymerase II-mediated transcription. Curr. Opin. Cell Biol. 16: 263-271.
78. Stadeli, R. and Basler, K. 2005. Dissecting nuclear Wingless signalling: Recruitment of the transcriptional co-activator Pygopus by a chain of adaptor proteins. Mech. Dev. 122: 1171-1182.
79. Stingl, J., Eirew, P., Ricketson, I., Shackleton, M., Vaillant, F., Choi, D., Li, H.I., and Eaves, C.J. 2006. Purification and unique properties of mammary epithelial stem cells. Nature 439: 993-997.
80. Su, I.H., Dobenecker, M.W., Dickinson, E., Oser, M., Basavaraj, A., Marqueron, R., Viale, A., Reinberg, D., Wulfing, C., and Tarakhovsky, A. 2005. Polycomb group protein ezh2 controls actin polymerization and cell signaling. Cell 121: 425-436.
81. Tago, K., Nakamura, T., Nishita, M., Hyodo, J., Nagai, S., Murata, Y., Adachi, S., Ohwada, S., Morishita, Y., Shibuya, H., et al. 2000. Inhibition of Wnt signaling by ICAT, a novel β-catenin-interacting protein. Genes & Dev. 14: 1741-1749.
82. Takeda, H., Lyle, S., Lazar, A.J., Zouboulis, C.C., Smyth, I., and Watt, F.M. 2006. Human sebaceous tumors harbor inactivating mutations in LEF1. Nat. Med. 12: 395-397.
83. Tenney, K. and Shilatifard, A. 2005. A COMPASS in the voyage of defining the role of trithorax/MLL-containing complexes: Linking leukemogensis to covalent modifications of chromatin. J. Cell. Biochem. 95: 429-436.
84. Teo, R., Mohrlen, F., Plickert, G., Muller, W.A., and Frank, U. 2006. An evolutionary conserved role of Wnt signaling in stem cell fate decision. Dev. Biol. 289: 91-99.
85. Thompson, B.J. 2004. A complex of Armadillo, Legless, and Pygopus coactivates dTCF to activate wingless target genes. Curr. Biol. 14: 458-466.
86. Thompson, B., Townsley, F., Rosin-Arbesfeld, R., Musisi, H., and Bienz, M. 2002. A new nuclear component of the Wnt signalling pathway. Nat. Cell Biol. 4: 367-373.
87. Townsley, F.M., Cliffe, A., and Bienz, M. 2004. Pygopus and Legless target Armadillo/β-catenin to the nucleus to enable its transcriptional co-activator function. Nat. Cell Biol. 6: 626-633.
88. Tutter, A.V., Fryer, C.J., and Jones, K.A. 2001. Chromatin-specific regulation of LEF-1-β-catenin transcription activation and inhibition in vitro. Genes & Dev. 15: 3342-3354.
89. Tybulewicz, V.L. 2005. Vav-family proteins in T-cell signalling. Curr. Opin. Immunol. 17: 267-274.
90. van de Wetering, M., Sancho, E., Verweij, C., de Lau, W., Oving, I., Hurlstone, A., van der Horn, K., Batlle, E., Coudreuse, D., Haramis, A.P., et al. 2002. The β-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell 111: 241-250.
91. Wiechens, N., Heinle, K., Englmeier, L., Schohl, A., and Fagotto, F. 2004. Nucleo-cytoplasmic shuttling of Axin, a negative regulator of the Wnt-β-catenin pathway. J. Biol. Chem. 279: 5263-5267.
92. Willert, K., Shibamoto, S., and Nusse, R. 1999. Wnt-induced dephosphorylation of axin releases β-catenin from the axin complex. Genes & Dev. 13: 1768-1773.
93. Willert, K., Brown, J.D., Danenberg, E., Duncan, A.W., Weissman, I.L., Reya, T., Yates III, J.R., and Nusse, R. 2003. Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature 423: 448-452.
94. Witte, V., Laffert, B., Rosorius, O., Lischka, P., Blume, K., Galler, G., Stilper, A., Willbold, D., D'Aloja, P., Sixt, M., et al. 2004. HIV-1 Nef mimics an integrin receptor signal that recruits the polycomb group protein Eed to the plasma membrane. Mol. Cell 13: 179-190.
95. Wysocka, J., Milne, T.A., and Allis, C.D. 2005a. Taking LSD 1 to a new high. Cell 122: 654-658.
96. Wysocka, J., Swigut, T., Milne, T.A., Dou, Y., Zhang, X., Burlingame, A.L., Roeder, R.G., Brivanlou, A.H., and Allis, C.D. 2005b. WDR5 associates with histone H3 methylated at K4 and is essential for H3 K4 methylation and vertebrate development. Cell 121: 859-872.
97. Xing, Y., Clements, W.K., Kimelman, D., and Xu, W. 2003. Crystal structure of a β-catenin/axin complex suggests a mechanism for the β-catenin destruction complex. Genes & Dev. 17: 2753-2764.
98. Xing, Y., Clements, W.K., Le Trong, I., Hinds, T.R., Stenkamp, R., Kimelman, D., and Xu, W. 2004. Crystal structure of a β-catenin/APC complex reveals a critical role for APC phosphorylation in APC function. Mol. Cell 15: 523-533.
99. Yamada, S., Pokutta, S., Drees, F., Weis, W.I., and Nelson, W.J. 2005. Deconstructing the cadherin-catenin-actin complex. Cell 123: 889-901.
100. Yamamoto, H., Kishida, S., Kishida, M., Ikeda, S., Takada, S., and Kikuchi, A. 1999. Phosphorylation of axin, a Wnt signal negative regulator, by glycogen synthase kinase-3β regulates its stability. J. Biol. Chem. 274: 10681-10684.
101. Yin, L., Wang, J., Klein, P.S., and Lazar, M.A. 2006. Nuclear receptor Rev-erbα is a critical lithium-sensitive component of the circadian clock. Science 311: 1002-1005.
102. Yokoyama, A., Wang, Z., Wysocka, J., Sanyal, M., Aufiero, D.J., Kitabayashi, I., Herr, W., and Cleary, M.L. 2004. Leukemia proto-oncoprotein MLL forms a SET1-like histone methyltransferase complex with menin to regulate Hox gene expression. Mol. Cell. Biol. 24: 5639-5649.
103. Zeng, X., Tamai, K., Doble, B., Li, S., Huang, H., Habas, R., Okamura, H., Woodgett, J., and He, X. 2005. A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation. Nature 438: 873-877.
104. Zhang, Q., Nottke, A., and Goodman, R.H. 2005. Homeodomain-interacting protein kinase -2 mediates CtBP phosphorylation and degradation in UV-triggered apoptosis. Proc. Natl. Acad. Sci. 102: 2802-2807.