TGF-β signaling and cancer: Structural and functional consequences of mutations in Smads

Molecular Medicine Today

Volumn 4, Issue 6, 1998, Pages 257-262

  Hata Phd, Akiko ^a   Massagué Phd, Joan ^a   Shi Phd, Yigong ^b  

^a HOWARD HUGHES MEDICAL INSTITUTE   (United States)

^b PRINCETON UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

TRANSFORMING GROWTH FACTOR BETA;

CANCER; GENE EXPRESSION REGULATION; GENE MUTATION; GENE TARGETING; HUMAN; NONHUMAN; REVIEW; SIGNAL TRANSDUCTION;

EID: 0344625381     PISSN: 13574310     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1357-4310(98)01247-7     Document Type: Review

References (46)

1. Massagué J. TGFβ signal transduction. Annu. Rev. Biochem. 67:1998;753-791.
2. Hogan B.L.M. Bone morphogenetic proteins: multifunctional regulators of vertebrate development. Genes Dev. 10:1996;1580-1594.
3. Kingsley D.M. The TGF-β superfamily: new members, new receptors, and new genetic tests of function in different organisms. Trends Genet. 10:1994;16-21.
4. Sekelsky J.J.et al. Genetic characterization and cloning of Mothers against dpp, a gene required for decapentaplegic function in Drosophila melanogaster. Genetics. 139:1995;1347-1358.
5. Savage C.et al. Caenorhabditis elegans genes sma-2, sma-3 and sma-4 define a conserved family of transforming growth factor β pathway components. Proc. Natl. Acad. Sci. U. S. A. 93:1996;790-794.
6. Heldin C-H., Miyazono K., ten Dijke P. TGF-β signalling from cell membrane to nucleus through SMAD proteins. Nature. 390:1997;465-471.
7. Liu F.et al. A human Mad protein acting as a BMP-regulated transcriptional activator. Nature. 381:1996;620-623.
8. Kretzschmar M.et al. The TGF-β family mediator Smad1 is phosphorylated directly and activated functionally by the BMP receptor kinase. Genes Dev. 11:1997;984-995.
9. Nishimura R.et al. Smad5 and DPC4 are key molecules in mediating BMP-2-induced osteoblastic differentiation of the pluripotent mesenchymal precursor cell line C2C12. J. Biol. Chem. 273:1998;1872-1879.
10. Chen Y., Bhushan A., Vale W. Smad8 mediates the signaling of the receptor serine kinase. Proc. Natl. Acad. Sci. U. S. A. 94:1997;12938-12943.
11. Eppert K.et al. MADR2 maps to 18q21 and encodes a TGFβ-regulated MAD-related protein that is functionally mutated in colorectal carcinoma. Cell. 86:1996;543-552.
12. Zhang Y., Feng X-H., Wu R-Y., Derynck R. Receptor-associated Mad homologues synergize as effectors of the TGFβ response. Nature. 383:1996;168-172.
13. Macias-Silva M.et al. MADR2 is a substrate of the TGFβ receptor and phosphorylation is required for nuclear accumulation and signaling. Cell. 87:1996;1215-1224.
14. Wisotzkey, R.G. et al. Medea is a Drosophila Smad4 homolog that is differentially required to potentiate DPP responses, Development (in press).
15. Hudson, J.B. et al. The Drosophila Medea gene is required downstream of dpp and encodes a functional homolog of human Smad4, Development (in press).
16. Das, P. et al. The Drosophila gene Medea demonstrates the requirement for different classes of Smads in dpp signaling, Development (in press).
17. Lagna G., Hata A., Hemmati-Brivanlou A., Massagué J. Partnership between DPC4 and SMAD proteins in TGFβ signalling pathways. Nature. 383:1996;832-836.
18. Liu F., Puponnot C., Massagué J. Dual role of the Smad4/DPC4 tumor suppressor in TGFβ-inducible transcriptional complexes. Genes Dev. 11:1997;3157-3167.
19. Chen X.et al. Smad4 and FAST-1 in the assembly of activin-responsive factor. Nature. 389:1997;85-89.
20. Topper J.N.et al. Vascular MADs: two novel MAD-related genes selectively inducible by flow in human vascular endothelium. Proc. Natl. Acad. Sci. U. S. A. 94:1997;9314-9319.
21. Hata A., Lagna G., Massagué J., Hemmati-Brivanlou A. Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor. Genes Dev. 12:1998;186-197.
22. Hayashi H.et al. The MAD-related protein associates with the TGFβ receptor and functions as an antagonist of TGFβ signaling. Cell. 89:1997;1165-1173.
23. Nakao A.et al. Identification of Smad7, a TGFβ-inducible antagonist of TGF-β signalling. Nature. 389:1997;631-635.
24. Tsuneizumi K.et al. Daughters against dpp modulates dpp organizing activity in Drosophila wing development. Nature. 389:1997;627-631.
25. Hata A.et al. Mutations increasing autoinhibition inactivate tumour suppressors Smad2 and Smad4. Nature. 388:1997;82-87.
26. Wu R-Y.et al. Heteromeric and homomeric interactions correlate with signaling activity and functional cooperativity of Smad3 and Smad4/DPC4. Mol. Cell. Biol. 17:1997;2521-2528.
27. Kim J.et al. Drosophila Mad binds to DNA and directly mediates activation of vestigial by Decapentaplegic. Nature. 388:1997;304-308.
28. Chen X., Rubock M.J., Whitman M. A transcriptional partner of MAD proteins in TGF-β signalling. Nature. 383:1996;691-696.
29. Baker J., Harland R.M. A novel mesoderm inducer, mMadr-2, functions in the activin signal transduction pathway. Genes Dev. 10:1996;1880-1889.
30. Shi Y.et al. A structural basis for mutational inactivation of the tumour suppressor Smad4. Nature. 388:1997;87-93.
31. Thomas J.T.et al. A human chondrodysplasia due to a mutation in a TGF-β superfamily member. Nat. Genet. 12:1996;315-317.
32. Guerrier D.et al. The persistent Mullerian duct syndrome: a molecular approach. J. Clin. Endocrinol. Metab. 68:1989;46-52.
33. Marchuk D.A. The molecular genetics of hereditary hemorrhagic telangiectasia. Chest. 111:1997;79S-82S.
34. Border W.A., Ruoslahti E. Transforming growth factor-β in disease: the dark side of tissue repair. J. Clin. Invest. 90:1992;1-7.
35. Alexandrow M.G., Moses H.L. Transforming growth factor β and cell cycle regulation. Cancer Res. 55:1995;1452-1457.
36. Markowitz S.D., Roberts A.B. Tumor suppressor activity of the TGF-β pathway in human cancers. Cytokine Growth Factor Rev. 7:1996;93-102.
37. Markowitz S.et al. Inactivation of the type II TGF-β receptor in colon cancer cells with microsatellite instability. Science. 268:1995;1336-1338.
38. Hahn S.A.et al. DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science. 271:1996;350-353.
39. Takagi Y.et al. Somatic alterations in the DPC4 gene in human colorectal cancers in vivo. Gastroenterology. 111:1996;1369-1372.
40. MacGrogan D., Pegram M., Slamon D., Bookstein R. Comparative mutations analysis of DPC4 (Smad4) in prostatic and colorectal carcinomas. Oncogene. 15:1997;1111-1114.
41. Schutte M.et al. DPC4 gene in various tumor types. Cancer Res. 56:1996;2527-2530.
42. Kim S.K.et al. DPC4, a candidate tumor suppressor gene, is altered infrequently in head and neck squamous cell carcinoma. Cancer Res. 56:1996;2519-2521.
43. Lei J.et al. Infrequent DPC4 gene mutation in esophageal cancer, gastric cancer and ulcerative colitis-associated neoplasms. Oncogene. 13:1996;2459-2462.
44. Uchida K.et al. Somatic in vivo alterations of the JV18-1 gene at 18q21 in human lung cancers. Cancer Res. 56:1996;5583-5585.
45. Riggins G.J.et al. Mad-related genes in the human. Nat. Genet. 13:1996;347-349.
46. Lo R.S.et al. The L3 loop: a structural motif determining specific interactions between SMAD proteins and TGF-β receptors. EMBO J. 17:1998;996-1005.