The Smad pathway in TGF-beta signalling

• Autorzy: Piestrzeniewicz D. , Brys M. , Krajewska W.M.
• Języki publikacji: EN

Abstrakty

EN

The recent identification of the Smad proteins has allowed the delineation of a mechanism by which TGF-β and related growth and differentiation factors convey their signals from transmembrane receptors into nucleus. Following receptor-induced activation heteromeric Smad complexes translocate into the nucleus where they act as transcription factors. Smad proteins modulate target genes through interaction with DNA and with other nuclear factors. Disruption of signalling cascade by Smad gene aberrations may cause loss of cellular responsiveness to TGF-β and thus contribute to development of cancer.

Słowa kluczowe

EN

Smad family; transforming growth factor-beta; signal transduction; nucleus; Smad protein; transmembrane receptor

• Wydawca: -
• Czasopismo: Cellular and Molecular Biology Letters
• Rocznik: 2000
• Tom: 05
• Numer: 3
• Opis fizyczny: p.381-396,fig.

Twórcy

autor

Piestrzeniewicz D.

• University of Lodz, Banacha 12-16, 90-237 Lodz, Poland

autor

Brys M.

autor

Krajewska W.M.

Bibliografia

• 1. Kingsley, D. M. The TGF-β superfamily: new members, new receptors, and new genetic tests of function in different organisms. Genes Dev. 8 (1994) 133-146.
• 2. Haralson, M. A. Transforming growth factor-β, other growth factors, and the extracellular matrix. J. Lab. Clin. Med. 130 (1997) 455-458.
• 3. Heldin, C-H., Myiazono, K. and ten Dijke, P. TGF-β signalling from cell membrane to nucleus through SMAD proteins. Nature 390 (1997) 465-471.
• 4. Hoodless, P. A. and Wrana, J. L. Mechanism and function of signaling by the TGFβ superfamily. In Protein Modeules in Signal Transduction, (Pawson A. J., Ed.) Springer-Verlag, Munchen 228 (1997) 235-272.
• 5. Josso, N. and di Clemente, N. Serine/threonine kinase receptors and ligands. Curr. Opin. Genet. Dev. 7 (1997) 371-377.
• 6. Attisano, L. and Wrana, J. L. Mads and Smads in TGFβ signalling. Curr. Opin. Cell. Biol. 10 (1998) 188-194.
• 7. Hata, A., Shi, Y. and Massague, J. TGF-β signaling and cancer: structural and functional consequences of mutations in Smads. Mol. Med. Today 4 (1998) 257-262.
• 8. Hu, P. P-C., Datto, M. B. and Wang, X-F. Molecular mechanisms of transforming growth factor-β signaling. Endocrine Rev. 19 (1998) 349- 363.
• 9. Kretzschmar, M. and Massague, J. SMADs: mediators and regulators of TGF-β signalling. Curr. Opin. Genet. Dev. 8 (1998) 103-111.
• 10. Massague, J. TGF-β signal transduction. Annu. Rev. Biochem. 67 (1998) 753-791.
• 11. Kawabata, M. and Miyazono, K. Signal Transduction of the TGF-β superfamily by Smad proteins, J. Biochem. (Tokyo) 125 (1999) 9-16.
• 12. Sekelsky, J. J., Newfeld, S. J., Raftery, L. A., Chartoff, E. H. and Gelbart, W. M. Genetic characterisation and cloning of Mothers against dpp, a gene required for decapentaplegic function in Drosophila melanogaster. Genetics 139 (1995) 1347-1358.
• 13. Savage, C., Das, P., Finelli, A. L., Townsend, S. R., Sun, C-Y., Baird, S. E. and Padget, R. W. Caenorhabditis elegans genes sma2, sma-3, and sma-4 define a conserved family of transforming growth factor beta pathway components. Proc. Natl. Acad. Sci. USA 93 (1996) 790-794.
• 14. Abdollah, S., Macias-Silva, M., Tsukazaki, T., Hayashi, H., Attisano, L. and Wrana, J. L. TβR1 phosphorylation of Smad2 on Ser465 and Ser467 is required for Smad2/Smad4 complex formation and signalling. J. Biol. Chem. 272 (1997) 27678-27685.
• 15. Shi, Y., Wang, Y-F., Jayaraman, L., Yang, H., Massague, J. and Pavletich, N. P. Crystal structure of a Smad MH1 domain bound to DNA: insights on DNA binding in TGF-β signalling. Cell 94 (1998) 585-594.
• 16. Zawel, L., Dai, J. L., Buckhaults, P., Zhou, S., Kinzler, K. W., Vogelstein, B. and Kern, S. E. Human Smad3 and Smad4 are sequence-specific transcription activators. Molecular Cell 1 (1998) 611-617.
• 17. Johnson, K., Kirkpatrick, H., Comer, A., Hoffmann, F. M. and Laughon, A. Interaction of Smad complexes with tripartite DNA-binding sites. J. Biol. Chem. 274 (1999) 20709-20716.
• 18. Yagi, K., Goto, D., Hamamoto, T., Takenoshita, S., Kato, M. and Miyazono, K. Alternatively spliced variant of Smad2 lacking exon 3. J. Biol. Chem. 274 (1999) 703-709.
• 19. Wu, G., Chen, Y-G., Ozdamar, B., Gyuricza, C. A., Chong, P. A., Wrana, J. L., Massague, J. and Shi, Y. Structural basis of Smad2 recognition by the Smad anchor for receptor activation. Science 287 (2000) 92-97.
• 20. Shi, Y., Hata, A., Lo, R. S., Massague, J. and Paveltich N. P. A structural basis for mutational inactivation of the tumour suppressor Smad4. Nature 388 (1997) 87-92.
• 21. de Caestecker, M. P., Hemmati, P., Larisch-Bloch, S., Ajmera, R., Roberts, A. B. and Lechleider, R. J. Characterization of functional domains within Smad4/DPC4. J. Biol. Chem. 272 (1997) 13690-13696.
• 22. de Caestecker, M. P., Yahata, T., Wang, D., Parks, W. T., Huang, S., Shioda, T., Roberts, A. B., Lechleider, R. J. The Smad4 Activation Domain (SAD) is a proline-rich, p300-dependent transcriptional activation domain. J. Biol. Chem. 275 (2000) 2115-2122.
• 23. Lo, R. S., Chen, Y-G., Shi, Y., Pavletich, N. P. and Massague, J. The L3 loop: a structural motif determining specific interactions between SMAD proteins and TGF-β receptors. EMBO J. 17 (1998) 996-1005.
• 24. Chen, Y-G., Hata, A., Lo, R. S., Wotton, D., Shi, Y., Pavletich, N. P. and Massague, J. Determinants of specifity in TGF-β signal transduction. Genes Dev. 12 (1998) 2144-2152.
• 25. Lagna, G. and Hemmati-Brivanlou, A. A molecular basis for Smad specificity. Develop. Dyn. 214 (1999) 269-277.
• 26. Chen, X., Weisberg, E., Fridmacher, V., Watanabe, M., Naco, G. and Whitman, M. Smad4 and FAST-1 in the assembly of activin-responsive factor. Nature 389 (1997) 85-89.
• 27. Souchelnytskyi, S., Tamaki, K., Engstrsöm, U., Wernstedt, C., ten Dijke P. and Heldin, C-H. Phosphorylation of Ser465 and Ser467 in the C terminus of Smad2 mediates interaction with Smad4 and is required for transforming growth factor -β signalling. J. Biol. Chem. 272 (1997) 28107-28115.
• 28. Tsukazaki, T., Chiang, T. A., Davison, A. F., Attisano, L. and Wrana, J. L. SARA, a FYVE domain protein that recruits Smad2 to the TGFβ receptor. Cell 95 (1998) 779-791.
• 29. Padgett, R. W. Intracellular signaling: Fleshing out the TGFβ pathway. Curr. Biol. 9 (1999) R408-R411.
• 30. Hayashi, H., Abdollah, S., Qui, Y., Cai, J., Xu, Y-Y., Grinnell, B. W., Richardson, M. A., Topper, J. N., Gimbrone Jr., M. A., Wrana, J. L. and Falb, D. The MAD-related protein Smad7 Associates with the TGFβ receptor and functions as an antagonist of TGFβ signaling. Cell 89 (1997) 1165-1173.
• 31. Imamura, T., Takase, M., Nishihara, A., Oeda, E., Hanai, J., Kawabata, M. and Miyazono, K. Smad6 inhibits signalling by the TGF-β superfamily. Nature 389 (1997) 622-626.
• 32. Nakao, A., Afrakhte, M., Moren, A., Nakayama, T., Christian, J. L., Heuchel, R., Itoh, S., Kawabata, M., Heldin, N-E., Heldin, C-H. and ten Dijke P. Identification of Smad7, a TGF-β inducible antagonist of TGF-β signalling. Nature 389 (1997) 631-635.
• 33. Christian, J. L. and Nakayama, T. Can’t get no SMADisfaction: Smad proteins as positive and negative regulators of TGF-β family signals. BioEssays 21 (1999) 382-390.
• 34. Hata, A., Lagna, G., Massague, J. and Hemmati-Brivanlou, A. Smad6 inhibits BMP/Smad1 signalling by specifically competing with the Smad4 tumour suppressor. Genes Dev. 12 (1998) 186-197.
• 35. Derynck, R., Zhang, Y. and Feng, X-H. Smads: transcriptional activators of TGF-β Responses. Cell 95 (1998) 737-740.
• 36. Chen, X., Rubock, M. J. and Whitman, M. A transcriptional partner for Mad proteins in TGF-β signalling. Nature 383 (1996) 691-696.
• 37. Liu, F., Pouponnot, C. and Massague, J. Dual role of the Smad4/DPC4 tumor suppressor in TGF-β-inducible transcriptional complexes. Genes Dev. 11 (1997) 3157-3167.
• 38. Labbe, E., Silvestri, C., Hoodless, P. A., Wrana, J. L. and Attisano, L. Smad2 and Smad3 positively and negatively regulate TGFβ-dependent transcription trough the forkhead DNA-binding protein FAST2. Molecular Cell 2 (1998) 109-120.
• 39. Nagarajan, R. P., Liu, J. and Chen, Y. Smad3 inhibits transforming growth factor-β and activin signaling by competing with Smad4 for FAST-2 binding. J. Biol. Chem. 274 (1999) 31229-31235.
• 40. Liberati, N. T., Datto, M. B., Frederick, J. P., Shen, X., Wong, C., Rougier-Chapman, E. M. and Wang, X-F. Smads bind directly to the Jun family of AP-1 transcription factors. Proc. Natl. Acad. Sci. USA 96 (1999) 4844-4849.
• 41. Hua, X., Liu, X., Ansari, D. O. and Lodish, H. F. Synergistic cooperation of TFE3 and Smad proteins in TGF-β-induced transcription of the plasminogen activator inhibitor-1 gene. Genes Dev. 12 (1998) 3084-3095.
• 42. Hua, X., Miller, Z. A., Wu, G., Shi, Y. and Lodish, H. F. Specifity in transforming growth factor β-induced transcription of the plasminogen activator inhibitor-1 gene: Interactions of promoter DNA, transcription factor µE3, and Smad proteins. Proc. Natl. Acad. Sci. USA 96 (1999) 13130-13135.
• 43. Moustakas, A. and Kardassis, D. Regulation of the human p21/WAF1/Cipl promoter in hepatic cells by functional interactions between Spl and Smad family members. Proc. Natl. Acad. Sci. USA 95 (1998) 6733-6738.
• 44. Hanai, J-i., Chen, L. F., Kanno, T., Ohtani-Fujito, N., Kim, W. Y., Guo, W-H., Imamura, T., Ishidou, Y., Fukuchi, M., Shi, M-J., Stavnezer, J., Kawabata, M., Miyazono, K. and Ito, Y. Interaction and functional cooperation of PEBP2/CBF with Smads. J. Biol. Chem. 274 (1999) 31577- 31582.
• 45. Wotton, D., Lo, R. S., Swaby, L-A. C. and Massague, J. Multiple modes of repression by the Smad transcriptional corepressor TGIF. J. Biol. Chem. 274 (1999) 37105-37110.
• 46. Verschueren, K., Remacle, J. E., Collart, C., Kraft, H., Baker, B. S., Tylzanowski, P., Nelles, L., Wuytens, G., Su, M-T., Bodmer, R., Smith, J. C. and Huylebroeck, D. SIP1, a novel zinc finger/homeodomain repressor, interacts with Smad proteins and binds to 5’-CACCT sequences in candidate target genes. J. Biol. Chem. 274 (1999) 20489-20498.
• 47. Akiyoshi, S., Inoune, H., Hanai, J-i., Kusanagi, K., Nemoto, N., Miyazono, K. and Kawabata, M. c-Ski acts as a transcriptional co-repressor in transforming growth factor-β signaling through interactions with Smads. J. Biol. Chem. 274 (1999) 35269-35277.
• 48. Luo, K., Stroschein, S. L., Wang, W., Chen, D., Martens, E., Zhou, S. and Zhou, Q. The ski oncoprotein interacts with the Smad proteins to repress TGF beta signaling. Genes Dev. 13 (1999) 2196-2206.
• 49. Stroschein, S. L., Wang, W., Zhou, S., Zhou, Q. and Luo, K. Negative feedback regulation of TGF-β signaling by the SnoN oncoprotein. (1999) Science 286 (1999) 771-774.
• 50. Sun, Y., Liu, X., Ng-Eaton, E., Lodish, H. F. and Weinberg, R. A. SnoN and Ski protooncoproteins are rapidly degraded in response to transforming growth factor β signaling. (1999) Proc. Natl. Acad. Sci. USA 96 12442-12447.
• 51. Feng, X-H., Zhang, Y., Wu, R-Y. and Denryck, R. The tumor suppressor Smad4/DPC4 and transcriptional adaptor CBP/p300 are coactivators for Smad3 in TGF-β-induced transcriptional activation. Genes Dev. 12 (1998) 2153-2163.
• 52. Janknecht, R., Wells, N. J. and Hunter, T. TGF-β-stimulated cooperation of Smad proteins with the coactivators CBP/p300. Genes Dev. 12 (1998) 2114-2119.
• 53. Pouponnot, C., Jayaraman, L. and Massague, J. Physical and functional interaction of SMADs and p300/CBP. J. Biol. Chem. 273 (1998) 22865- 22868.
• 54. Shen, X., Hu, P. P-c., Liberati, N. T., Datto, M. B., Frederick, J. P. and Wang X-F. TGF-β-induced phosphorylation of Smad3 regulates its interaction with coactivator p300/CREB-binding protein. Mol. Biol. Cell. 9 (1998) 3309-3319.
• 55. Shioda, T., Lechleider, R. J., Dunwoodie, S. L., Li, H., Yahata, T., de Caestecker, M. P., Fenner, M. H., Roberts, A. B. and Isselbacher K. J. Transcriptional activating activity of Smad4: roles of SMAD hetero-oligomerization and enhancement by an associating transactivator. Proc. Natl. Acad. Sci. USA 95 (1998) 9785-9790.
• 56. Wotton, D., Lo, R. S., Lee, S. and Massague, J. A Smad transcriptional corepressor. Cell 97 (1999) 29-39.
• 57. Nishihara, A., Hanai, J-i., Imamura, T., Miyazono, K. and Kawabata, M. E1A inhibits transforming growth factor-β signaling through binding to Smad proteins. J. Biol. Chem. 274 (1999) 28716-28723.
• 58. Kurokawa, M., Mitani, K., Irie, K., Matsuyama, T., Takahashi, T., Chiba, S., Yazaki, Y., Matsumoto, K. and Hirai, H. The oncoprotein Evi-1 represses TGF-β signalling by inhibiting Smad3. Nature 394 (1998) 92-96.
• 59. Yam, C. H., Siu, W. Y., Arooz, T., Chiu, C. H. S., Lau, A., Wang, X. Q. and Poon, R. Y. C. MDM2 and MDMX inhibit the transcriptional activity of ectopically expressed SMAD proteins. Cancer Res. 59 (1999) 5075- 5078.
• 60. Eppert, K., Scherer, S. W., Ozcelik, H., Pirone, R., Hoodless, P., Kim. H., Tsui, L-Ch.,bapat, B., Gallinger, S., Andrulis, I. L., Thomsen, G. H., wrana, J. L. and Attisano, L. MADR2 maps to 18q21 and encodes a TGFβ- regulated MAD-related protein that is functionally mutated in colorectal carcinoma. Cell 86 (1996) 543-552.
• 61. Hahn, S. A., Schutte, M., Hoque, A. T., Mosaluk, C. A., da Costa, L. T., Rozenblum, E., Weinstein, C. L., Fisher, A., Yeo, C. J., Hurban, R. H. and Kern, S. E. DPC4, a candidate tumor supressor gene at human chromosome 18q21.1. Science 271 (1996) 350-353.
• 62. Riggins, G. J., Thiagalingam, S., Rozenblum, E., Weinstein, C. L., Kern, S. E,. Hamilton, S. R., Wilson, J. V. K., Markowitz, S. D., Kinzler, K. W. and Vogelstein, B. Mad-related genes in human. Nature Genet. 13 (1996) 347-349.
• 63. Hata, A., Lo, R. S., Wotton, D., Lagna, G. and Massague, J. Mutations increasing autoinhibition inactivate tumour suppressors Smad2 and Smad4. Nature 388 (1997) 82-87.
• 64. Riggins, G. J., Kinzler, K. W., Vogelstein, B. and Thiagalingam, S. Frequency of Smad gene mutations in human cancers. Cancer Res. 57 (1997) 2578-2580.
• 65. Bevan, S., Woodford-Richens, K., Rozen, P., Eng, C., Young, J., Dunlop, M., Neale, K., Phillips, R., Markie, D., Rodriguez-Bigas, M., Leggett, B., Sheridan, E., Hodgson, S., Jwama, T., Eccles, D., Bodmer, W., Houlston, R. and Tomlinson, I. Screening SMAD1, SMAD2, SMAD3, and SMAD5 for germline mutations in juvenile polyposis syndrome. Gut 45 (1999) 406-408.
• 66. Nakao, A., Röijer, E., Imamura, T., Souchelnytskyi, S., Stenman, G., Heldin, C-H., ten Dijke, P. Identification of Smad2, a human Mad-related protein in the transforming growth factor β signaling pathway. J. Biol. Chem. 272 (1997) 2896-2900.
• 67. Takenoshita, S., Mogi, A., Nagashima, M., Yang, K., Yagi, K., Hanyu, A., Nagamachi, Y., Myizono, K. and Hagiwara, K. Characterization of the MADH2/Smad2 gene, a human Mad homolog responsible for the Transforming growth factor-β and Activin signal transduction pathway. Genomics 48 (1998) 1-11.
• 68. Takagi, Y., Koumura, H., Futamura, M., Aoki, S., Ymaguchi, K., Kida, H., Tanemura, H., Shimokawa, K. and Saji, S. Somatic alterations of the SMAD-2 gene in human colorectal cancers. Br. J. Cancer 78 (1998) 1152- 1155.
• 69. Uchida, K., Nagatake, M., Osada, H., Yatabe, Y., Kondo, M., Mitsudomi, T., Masuda, A., Takahashi, T. and Takahashi, T. Somatic in vivo alterations of the JV18-1 gene at 18q21 in human lung cancers. Cancer Res. 56 (1996) 5583-5585.
• 70. Yakicier, M. C., Irmak, M. B., Romano, A., Kew, M. and Ozturk, M. Smad2 and Smad4 gene mutations in hepatocellular carcinoma. Oncogene 18 (1999) 4879-4883.
• 71. Prunier, C., Mazars, A., Noë, V., Bruyneel, E., Mareel, M., Gespach, Ch. and Atfi, A. Evidence that Smad2 is a tumor suppressor implicated in the control of cellular invasion. J. Biol. Chem. 274 (1999) 22919-22922.
• 72. Duff, E. K. and Clarke, A. R. Smad4 (DPC4)-a potent tumour suppressor. Br.J. Cancer 78 (1998) 1615-1619.
• 73. Jonson, T., Gorunova, L., Dawiskiba, S., Andren-Sandberg, A., Stenman, G., ten Dijke, P., Johansson, B. and Höglund, M. Molecular analyses of the 15q and 18q SMAD genes in pancreatic cancer. Genes Chromosom. Cancer 24 (1999) 62-71.
• 74. Schutte, M., Hurban, R. H., Hedrick, L., Cho, K. R., Nadasady, G. M., Weinstein, C. L., Bova, G. S., Isaacs, W. B., Cairns, P., Nawroz, H., Sidransky, D., Casero Jr., R. A., Meltzer, P. S., Hahn, S. A. and Kern, S. E. DPC4 gene in various tumor types. Cancer Res. 56 (1996) 2527-2530.
• 75. Zhou, Y., Kato, H., Shan, D., Minami, R., Kitazawa, S., Matsuda, T., Arima, T., Barrett, J. C. and Wake, N. Involvement of mutations in the DPC4 promoter in endometrial carcinoma development. Mol. Carcinogen. 25 (1999) 64-72.
• 76. MacGrogan, D., Pegram, M., Slamon, D. and Brookstein, R. Comparative mutations analysis of DPC4 (Smad4) in prostatic and colorectal carcinomas. Oncogene 15 (1997) 1111-1114.
• 77. Nagatake, M., Takagi, Y., Osada, H., Uchida, K., Mitsudomi, T., Saji, S., Shimatokata, K., Takahashi, T. and Takahasi, T. Somatic in vivo alterations of the DPC4 gene at 18q21 in human lung cancers. Cancer Res. 56 (1996) 2718-2720.
• 78. Kim, S. K., Fan, Y., Papadimitrakopoulou, V., Clayman, G., Hittelman, W. N., Hong, W. K., Lotan, R. and Mao, L. DPC4, a candidate tumor suppressor gene, is altered infrequently in head and neck squamous cell carcinoma. Cancer Res. 56 (1996) 2519-2521.
• 79. Lei, J., Zou, T. T., Shi, Y. O. Infrequent DPC4 gene mutation in esophageal cancer, gastric cancer and ulcerative colitis-associated neoplasms. Oncogene 13 (1996) 2459-2462.
• 80. Nizhizuka, S., Tamura, G., Maesawa, C. Analysis of the DPC4 gene in gastric carcinoma. Jpn. J. Cancer Res. 88 (1997) 335-339.
• 81. Takagi, Y., Kohmura, H., Futamura, M., Kida, H., Tanemura, H., Shimokawa, K. and Saji S. Somatic alterations of the DPC4 gene in human colorectal cancers in vivo. Gastrenterology 111 (1996) 1369-1372.
• 82. Miyaki, M., Iijima, T., Konishi, M., Sakai, K., Ishii, A., Yasuno, M., Hishima, T., Koike, M., Shitara, N., Iwama, T., Utsunomiya, J., Kuroki, T. and Mori, T. Higher frequency of Smad4 gene mutation in human colorectal cancer with distant metastasis. Oncogene 18 (1999) 3098-3103.
• 83. Howe, J. R., Ringold, J. C., Hughes, J. H. and Summers, R. W. Direct genetic testing for Smad4 mutations in patients at risk for juvenile polyposis. Surgery 126 (1999) 162-170.
• 84. Roth, S., Sistonen, P., Salovaara, R., Hemminki, A., Loukola, A., Johansson, M., Avizienyte, E., Cleary, K. A., Lynch, P., Amos, C. I., Kristo, P., Mecklin, J-P., Kellokumpu, I., Järvinen, H. and Aaltonen, L. A. SMAD genes in juvenile polyposis. Genes Chromosom. Cancer 26 (1999) 54-61.
• 85. Le Dai, J., Tumacioglu, K. K., Schutte, M., Sugar, A. Y., Kern, S. E. Dpc4 transcriptional activation and dysfunction in cancer cells. Cancer Res. 58 (1998) 4592-4597.