Axin and GSK3-β control Smad3 protein stability and modulate TGF-β signaling

Genes and Development

Volumn 22, Issue 1, 2008, Pages 106-120

  Guo, Xing ^a   Ramirez, Alejandro ^b   Waddell, David S ^a,c   Li, Zhizhong ^a   Liu, Xuedong ^b   Wang, Xiao Fan ^a  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

^b UNIVERSITY OF COLORADO   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Axin; GSK3 ; Protein stability; Smad3; TGF ; Ubiquitination

Indexed keywords

AXIN; GLYCOGEN SYNTHASE KINASE 3BETA; SMAD3 PROTEIN; TRANSFORMING GROWTH FACTOR BETA; AXIN PROTEIN; GLYCOGEN SYNTHASE KINASE 3; POLYUBIQUITIN; PROTEASOME; REPRESSOR PROTEIN; THREONINE; UBIQUITIN PROTEIN LIGASE; UNCLASSIFIED DRUG; WNT PROTEIN;

ARTICLE; ENZYME ACTIVITY; GENETIC TRANSCRIPTION; HUMAN; HUMAN CELL; PHOSPHORYLATION; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN INTERACTION; PROTEIN STABILITY; UBIQUITINATION; CELL CULTURE; GENETICS; METABOLISM; SIGNAL TRANSDUCTION;

CELLS, CULTURED; GLYCOGEN SYNTHASE KINASE 3; HUMANS; PHOSPHORYLATION; POLYUBIQUITIN; PROTEASOME ENDOPEPTIDASE COMPLEX; REPRESSOR PROTEINS; SIGNAL TRANSDUCTION; SMAD3 PROTEIN; THREONINE; TRANSFORMING GROWTH FACTOR BETA; UBIQUITIN-PROTEIN LIGASES; WNT PROTEINS;

EID: 38149054804     PISSN: 08909369     EISSN: 15495477     Source Type: Journal    
DOI: 10.1101/gad.1590908     Document Type: Article

References (67)

1. Bierie, B. and Moses, H.L. 2006. Tumour microenvironment: TGFβ: The molecular Jekyll and Hyde of cancer. Nat. Rev. Cancer 6: 506-520.
2. Chen, H.B., Shen, J., Ip, Y.T., and Xu, L. 2006. Identification of phosphatases for Smad in the BMP/DPP pathway. Genes & Dev. 20: 648-653.
3. Clarke, D.C., Betterton, M.D., and Liu, X. 2006. Systems theory of Smad signalling. IEE Proc. Syst. Biol. 153: 412-424.
4. Cohen, P. and Frame, S. 2001. The renaissance of GSK3. Nat. Rev. Mol. Cell Biol. 2: 769-776.
5. Cross, D.A., Alessi, D.R., Cohen, P., Andjelkovich, M., and Hemmings, B.A. 1995. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 378: 785-789.
6. Dajani, R., Fraser, E., Roe, S.M., Yeo, M., Good, V.M., Thompson, V., Dale, T.C., and Pearl, L.H. 2003. Structural basis for recruitment of glycogen synthase kinase 3β to the axin-APC scaffold complex. EMBO J. 22: 494-501.
7. Dennler, S., Huet, S., and Gauthier, J.M. 1999. A short aminoacid sequence in MH1 domain is responsible for functional differences between Smad2 and Smad3. Oncogene 18: 1643-1648.
8. Duan, X., Liang, Y.-Y., Feng, X.-H., and Lin, X. 2006. Protein serine/threonine phosphatase PPM1A dephosphorylates Smad1 in the bone morphogenetic protein signaling pathway. J. Biol. Chem. 281: 36526-36532.
9. Dunn, N.R., Koonce, C.H., Anderson, D.C., Islam, A., Bikoff, E.K., and Robertson, E.J. 2005. Mice exclusively expressing the short isoform of Smad2 develop normally and are viable and fertile. Genes & Dev. 19: 152-163.
10. Frederick, J.P., Liberati, N.T., Waddell, D.S., Shi, Y., and Wang, X.-F. 2004. Transforming growth factor β-mediated transcriptional repression of c-myc is dependent on direct binding of Smad3 to a novel repressive Smad binding element. Mol. Cell. Biol. 24: 2546-2559.
11. Furuhashi, M., Yagi, K., Yamamoto, H., Furukawa, Y., Shimada, S., Nakamura, Y., Kikuchi, A., Miyazono, K., and Kato, M. 2001. Axin facilitates Smad3 activation in the transforming growth factor-β signaling pathway. Mol. Cell. Biol. 21: 5132-5141.
12. Guo, W. and Giancotti, F.G. 2004. Integrin signalling during tumour progression. Nat. Rev. Mol. Cell Biol. 5: 816-826.
13. Hannon, G.J. and Beach, D. 1994. pl5INK4B is a potential effector of TGF-β-induced cell cycle arrest. Nature 371: 257-261.
14. Hedgepeth, C.M., Deardorff, M.A., Rankin, K., and Klein, P.S. 1999. Regulation of glycogen synthase kinase 3β and downstream Wnt signaling by axin. Mol. Cell. Biol. 19: 7147-7157.
15. Heldin, C.H. and ten Dijke, P. 1999. SMAD destruction turns off signalling. Nat. Cell Biol. 1: E195-E197. doi: 10.1038/70223.
16. Heldin, C.-H., Miyazono, K., and Dijke, P. 1997. TGF-β signalling from cell membrane to nucleus through SMAD proteins. Nature 390: 465-471.
17. Hoeflich, K.P., Luo, J., Rubie, E.A., Tsao, M.S., Jin, O., and Woodgett, J.R. 2000. Requirement for glycogen synthase kinase-3β in cell survival and NF-κ-B activation. Nature 406: 86-90.
18. Hughes, K., Nikolakaki, E., Plyte, S.E., Totty, N.F., and Woodgett, J.R. 1993. Modulation of the glycogen synthase kinase-3 family by tyrosine phosphorylation. EMBO J. 12: 803-808.
19. Ilyas, M., Efstathiou, J.A., Straub, J., Kim, H.C., and Bodmer, W.F. 1999. Transforming growth factor β stimulation of colorectal cancer cell lines: Type II receptor bypass and changes in adhesion molecule expression. Proc. Natl. Acad. Sci. 96: 3087-3091.
20. Inman, G.J., Nicolas, F.J., and Hill, C.S. 2002. Nucleocytoplasmic shuttling of Smads 2, 3, and 4 permits sensing of TGF-β receptor activity. Mol. Cell 10: 283-294.
21. Inoue, Y., Kitagawa, M., Onozaki, K., and Hayashi, H. 2004. Contribution of the constitutive and inducible degradation of Smad3 by the ubiquitin-proteasome pathway to transforming growth factor-β signaling. J. Interferon Cytokine Res. 24: 43-54.
22. Izzi, L. and Attisano, L. 2006. Ubiquitin-dependent regulation of TGF signaling in cancer. Neoplasia 8: 677-688.
23. Jayaraman, L. and Massagué, J. 2000. Distinct oligomeric states of SMAD proteins in the transforming growth factor-β pathway. J. Biol. Chem. 275: 40710-40717.
24. Jian, H., Shen, X., Liu, I., Semenov, M., He, X., and Wang, X.F. 2006. Smad3-dependent nuclear translocation of β-catenin is required for TGF-β1-induced proliferation of bone marrowderived adult human mesenchymal stem cells. Genes & Dev. 20: 666-674.
25. Jope, R.S. and Johnson, G.V. 2004. The glamour and gloom of glycogen synthase kinase-3. Trends Biochem. Sci. 29: 95-102.
26. Kamaraju, A.K. and Roberts, A.B. 2005. Role of Rho/ROCK and p38 MAP kinase pathways in transforming growth factor-β-mediated Smad-dependent growth inhibition of human breast carcinoma cells in vivo. J. Biol. Chem. 280: 1024-1036.
27. Kang, Y., Chen, C.R., and Massagué, J. 2003a. A self-enabling TGFβ response coupled to stress signaling: Smad engages stress response factor ATF3 for Id1 repression in epithelial cells. Mol. Cell 11: 915-926.
28. Kang, Y., Siegel, P.M., Shu, W., Drobnjak, M., Kakonen, S.M., Cordon-Cardo, C., Guise, T.A., and Massague, J. 2003b. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 3: 537-549.
29. Kim, S.G., Kim, H.A., Jong, H.S., Park, J.H., Kim, N.K., Hong, S.H., Kim, T.Y., and Bang, Y.J. 2005. The endogenous ratio of Smad2 and Smad3 influences the cytostatic function of Smad3. Mol. Biol. Cell 16: 4672-4683.
30. Knockaert, M., Sapkota, G., Alarcon, C., Massague, J., and Brivanlou, A.H. 2006. Unique players in the BMP pathway: Small C-terminal domain phosphatases dephosphorylate Smad1 to attenuate BMP signaling. Proc. Natl. Acad. Sci. 103: 11940-11945.
31. Kretschmer, A., Moepert, K., Dames, S., Sternberger, M., Kaufmann, J., and Klippel, A. 2003. Differential regulation of TGF-β signaling through Smad2, Smad3 and Smad4. Oncogene 22: 6748-6763.
32. Labbe, E., Letamendia, A., and Attisano, L. 2000. Association of Smads with lymphoid enhancer binding factor 1/T cell-specific factor mediates cooperative signaling by the transforming growth factor-β and wnt pathways. Proc. Natl. Acad. Sci. 97: 8358-8363.
33. Labbe, E., Lock, L., Letamendia, A., Gorska, A.E., Gryfe, R., Gallinger, S., Moses, H.L., and Attisano, L. 2007. Transcriptional cooperation between the transforming growth factor-β and Wnt pathways in mammary and intestinal tumorigenesis. Cancer Res. 67: 75-84.
34. Lee, E., Salic, A., Krüger, 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. doi: 10.1371/journal.pbio.0000010.
35. Levy, L., Howell, M., Das, D., Harkin, S., Episkopou, V., and Hill, C.S. 2007. Arkadia activates Smad3/Smad4-dependent transcription by triggering signal-induced SnoN degradation. Mol. Cell. Biol. 27: 6068-6083.
36. Lin, X., Liang, M., Liang, Y.-Y., Brunicardi, F.C., Melchior, F., and Feng, X.-H. 2003. Activation of transforming growth factor-β signaling by SUMO-1 modification of tumor suppressor Smad4/DPC4. J. Biol. Chem. 278: 18714-18719.
37. Lin, X., Duan, X., Liang, Y.Y., Su, Y., Wrighton, K.H., Long, J., Hu, M., Davis, C.M., Wang, J., Brunicardi, F.C., et al. 2006. PPM1A functions as a Smad phosphatase to terminate TGFβ signaling. Cell 125: 915-928.
38. Liu, C., Li, Y., Semenov, M., Han, C., Baeg, G.-H., Tan, Y., Zhang, Z., Lin, X., and He, X. 2002. Control of β-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell 108: 837-847.
39. Liu, W., Rui, H., Wang, J., Lin, S., He, Y., Chen, M., Li, Q., Ye, Z., Zhang, S., Chan, S.C., et al. 2006. Axin is a scaffold protein in TGF-β signaling that promotes degradation of Smad7 by Arkadia. EMBO J. 25: 1646-1658.
40. Macheda, M.L., Rogers, S., and Best, J.D. 2005. Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer. J. Cell. Physiol. 202: 654-662.
41. Massagué, J. 2000. How cells read TGF-β signals. Nat. Rev. Mol. Cell Biol. 1: 169-178.
42. Matsuura, I., Denissova, N.G., Wang, G., He, D., Long, J., and Liu, F. 2004. Cyclin-dependent kinases regulate the antiproliferative function of Smads. Nature 430: 226-231.
43. Matsuura, I., Wang, G., He, D., and Liu, F. 2005. Identification and characterization of ERK MAP kinase phosphorylation sites in Smad3. Biochemistry 44: 12546-12553.
44. Morin, P.J., Sparks, A.B., Korinek, V., Barker, N., Clevers, H., Vogelstein, B., and Kinzler, K.W. 1997. Activation of β-catenin-Tcf signaling in colon cancer by mutations in β-catenin or APC. Science 275: 1787-1790.
45. Piek, E., Ju, W.J., Heyer, J., Escalante-Alcalde, D., Stewart, C.L., Weinstein, M., Deng, C., Kucherlapati, R., Bottinger, E.P., and Roberts, A.B. 2001. Functional characterization of transforming growth factor β signaling in Smad2- and Smad3-deficient fibroblasts. J. Biol. Chem. 276: 19945-19953.
46. Price, M.A. and Kalderon, D. 2002. Proteolysis of the Hedgehog signaling effector Cubitus interruptus requires phosphorylation by glycogen synthase kinase 3 and casein kinase 1. Cell 108: 823-835.
47. Roberts, A.B., Tian, F., Byfield, S., DaCosta, S.C., Ooshima, A., Saika, S., and Flanders, K.C. 2006. Smad3 is key to TGF-β-mediated epithelial-to-mesenchymal transition, fibrosis, tumor suppression and metastasis. Cytokine Growth Factor Rev. 17: 19-27.
48. Salahshor, S. and Woodgett, J.R. 2005. The links between axin and carcinogenesis. J. Clin. Pathol. 58: 225-236.
49. Sapkota, G., Knockaert, M., Alarcon, C., Montalvo, E., Brivanlou, A.H., and Massague, J. 2006. Dephosphorylation of the linker regions of Smad1 and Smad2/3 by small C-terminal domain phosphatases has distinct outcomes for bone morphogenetic protein and transforming growth factor-β pathways. J. Biol. Chem. 281: 40412-40419.
50. Sapkota, G., Alarcon, C., Spagnoli, F.M., Brivanlou, A.H., and Massague, J. 2007. Balancing BMP signaling through integrated inputs into the Smad1 linker. Mol. Cell 25: 441-454.
51. Satoh, S., Daigo, Y., Furukawa, Y., Kato, T., Miwa, N., Nishiwaki, T., Kawasoe, T., Ishiguro, H., Fujita, M., Tokino, T., et al. 2000. AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1. Nat. Genet. 24: 245-250.
52. Schilling, S.H., Datto, M.B., and Wang, X.F. 2006. A phosphatase controls the fate of receptor-regulated Smads. Cell 125: 838-840.
53. Schmierer, B. and Hill, C.S. 2005. Kinetic analysis of Smad nucleocytoplasmic shuttling reveals a mechanism for transforming growth factor β-dependent nuclear accumulation of Smads. Mol. Cell. Biol. 25: 9845-9858.
54. Shen, X., Li, J., Hu, P.P., Waddell, D., Zhang, J., and Wang, X.-F. 2001. The activity of guanine exchange factor NET1 is essential for transforming growth factor-β-mediated stress fiber formation. J. Biol. Chem. 276: 15362-15368.
55. Shi, Y. and Massagué, J. 2003. Mechanisms of TGF-β signaling from cell membrane to the nucleus. Cell 113: 685-700.
56. Shi, Y., Wang, Y.F., Jayaraman, L., Yang, H., Massagué, J., and Pavletich, N.P. 1998. Crystal structure of a Smad MH1 domain bound to DNA: Insights on DNA binding in TGF-β signaling. Cell 94: 585-594.
57. Siegel, P.M. and Massagué, J. 2003. Cytostatic and apoptotic actions of TGF-β in homeostasis and cancer. Nat. Rev. Cancer 3: 807-820.
58. van Es, J.H., Barker, N., and Clevers, H. 2003. You Wnt some, you lose some: Oncogenes in the Wnt signaling pathway. Curr. Opin. Genet. Dev. 13: 28-33.
59. Waddell, D.S., Liberati, N.T., Guo, X., Frederick, J.P., and Wang, X.-F. 2004. Casein kinase Iε plays a functional role in the transforming growth factor-β signaling pathway. J. Biol. Chem. 279: 29236-29246.
60. Webster, M.T., Rozycka, M., Sara, E., Davis, E., Smalley, M., Young, N., Dale, T.C., and Wooster, R. 2000. Sequence variants of the axin gene in breast, colon, and other cancers: An analysis of mutations that interfere with GSK3 binding. Genes Chromosomes Cancer 28: 443-453.
61. Weigelt, B., Peterse, J.L., and van't Veer, L.J. 2005. Breast cancer metastasis: Markers and models. Nat. Rev. Cancer 5: 591-602.
62. Weinstein, M., Yang, X., and Deng, C. 2000. Functions of mammalian Smad genes as revealed by targeted gene disruption in mice. Cytokine Growth Factor Rev. 11: 49-58.
63. Wrana, J.L., Attisano, L., Cárcamo, J., Zentella, A., Doody, J., Laiho, M., Wang, X.-F., and Massague, J. 1992. TGFβ signals through a heteromeric protein kinase receptor complex. Cell 71: 1003-1014.
64. 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.
65. Yagi, K., Goto, D., Hamamoto, T., Takenoshita, S., Kato, M., and Miyazono, K. 1999. Alternatively spliced variant of Smad2 lacking exon 3. Comparison with wild-type Smad2 and Smad3. J. Biol. Chem. 274: 703-709.
66. 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.
67. Zhao, Y., Altman, B.J., Coloff, J.L., Herman, C.E., Jacobs, S.R., Wieman, H.L., Wofford, J.A., Dimascio, L.N., Ilkayeva, O., Kelekar, A., et al. 2007. Glycogen synthase kinase 3α and 3β mediate a glucose-sensitive antiapoptotic signaling pathway to stabilize Mcl-1. Mol. Cell. Biol. 27: 4328-4339.