The Smads: Transcriptional regulation and mouse models

Cytokine and Growth Factor Reviews

Volumn 11, Issue 1-2, 2000, Pages 37-48

  Datto, M ^a   Wang, X F ^a  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Bone metabolism; Inflammation; Mouse models; Smads; TGF ; Transcription; Tumorigenesis

Indexed keywords

DNA BINDING PROTEIN; PROTEIN SERINE THREONINE KINASE; PROTEIN SMAD3; REPRESSOR PROTEIN; SMAD PROTEIN; SMAD1 PROTEIN; SMAD2 PROTEIN; SMAD4 PROTEIN; TRANSACTIVATOR PROTEIN; TRANSCRIPTION FACTOR; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA RECEPTOR;

ANIMAL; ANIMAL EXPERIMENT; ANIMAL MODEL; BONE; BONE METABOLISM; CARCINOGENESIS; EXPERIMENTAL NEOPLASM; GENETIC TRANSCRIPTION; GENETICS; HUMAN; IMMUNE SYSTEM; INFLAMMATION; METABOLISM; MOLECULAR CLONING; MOLECULAR GENETICS; MOUSE; MOUSE MUTANT; NONHUMAN; NUCLEOTIDE SEQUENCE; PATHOPHYSIOLOGY; PHYSIOLOGY; PROTEIN FAMILY; PROTEIN PHOSPHORYLATION; REVIEW; SIGNAL TRANSDUCTION; TRANSCRIPTION REGULATION;

ANIMALS; BASE SEQUENCE; BONE AND BONES; DNA-BINDING PROTEINS; HUMANS; IMMUNE SYSTEM; MICE; MICE, MUTANT STRAINS; MOLECULAR SEQUENCE DATA; NEOPLASMS, EXPERIMENTAL; REPRESSOR PROTEINS; SMAD PROTEINS; SMAD2 PROTEIN; SMAD3 PROTEIN; SMAD4 PROTEIN; TRANS-ACTIVATORS; TRANSCRIPTION FACTORS; TRANSCRIPTION, GENETIC; TRANSFORMING GROWTH FACTOR BETA;

ANIMALIA;

EID: 0034023701     PISSN: 13596101     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1359-6101(99)00027-1     Document Type: Review

References (110)

1. Letterio J.J., Roberts A.B. Regulation of immune responses by TGF-β Annu. Rev. Immunol. 16:1998;137-161.
2. O'Kane S., Ferguson M.W. Transforming growth factor-βs and wound healing. Int. J. Biochem. Cell Biol. 29:1997;63-78.
3. Border W.A., Noble N.A. Transforming growth factor-β in tissue fibrosis. N. Engl. J. Med. 331:1994;1286-1292.
4. 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.
5. Akhurst R.J., Balmain A. Genetic events and the role of TGF-β in epithelial tumour progression. J. Pathol. 187:1999;82-90.
6. Moses H.L., Serra R. Regulation of differentiation by TGF-β Curr. Opin. Genet. Dev. 6:1996;581-586.
7. Roberts A.B. Molecular and cell biology of TGF-β Miner Electrolyte Metab. 24:1998;111-119.
8. Hu P.P.-C., Datto M.B., Wang X.-F. Molecular mechanisms of transforming growth factor-β signaling. Endocrine Rev. 19:1998;349-363.
9. Massague J. TGF-β signal transduction. Annu. Rev. Biochem. 67:1998;753-791.
10. Attisano L., Wrana J.L., Lopez-Casillas F., Massague J. TGF-β receptors and actions. Biochim. Biophys. Acta. 1222:1994;71-80.
11. Sekelsky J.J., Newfeld S.J., Raftery L.A., Chartoff E.H., Gelbart W.M. Genetic characterization and cloning of mothers against dpp, a gene required for decapentaplegic function in Drosophila melanogaster. Genetics. 139:1995;1347-1358.
12. Raftery L.A., Twombly V., Wharton K., Gelbart W.M. Genetic screens to identify elements of the decapentaplegic signaling pathway in Drosophila. Genetics. 139:1995;241-254.
13. Savage C., Das P., Finelli A.L., Townsend S.R., Sun C.Y., Baird S.E., Padgett R.W. Caenorhabditis elegans genes sma-2, sma-3, sma-4 define a conserved family of transforming growth factor β pathway components. Proc. Natl. Acad. Sci. USA. 93:1996;790-794.
14. Eppert K., Scherer S.W., Ozcelik H., Pirone R., Hoodless P., Kim H., Tsui L.C., Bapat B., Gallinger S., Andrulis I.L., Thomsen G.H., Wrana J.L., 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.
15. Hoodless P.A., Haerry T., Abdollah S., Stapleton M., O'Connor M.B., Attisano L., Wrana J.L. MADR1, a MAD-related protein that functions in BMP2 signaling pathways. Cell. 85:1996;489-500.
16. Lechleider R.J., de Coestecker M.P., Dehejia A., Polymeropoulos M.H., Roberts A.B. Serine phosphorylation, chromosomal localization and transforming growth factor-β signal transduction by human bsp-1. J. Biol. Chem. 271:1996;17617-17620.
17. Liu F., Hata A., Baker J.C., Goody J., Carcamo J., Harland R.M., Massague J. A human Mad protein acting as a BMP-regulated transcriptional activator. Nature. 381:1996;620-623.
18. Yingling J.M., Das P., Savage C., Zhang M., Padgett R.W., Wang X.-F. Mammalian dwarfins are phosphorylated in response to TGF-β and are implicated in control of cell growth. Proc. Natl. Acad. Sci. USA. 93:1996;8940-8944.
19. Zhang Y., Feng X., We R., Derynck R. Receptor-associated Mad homologues synergize as effectors of the TGF-β response. Nature. 383:1996;168-272.
20. Hahn S.A., Schutte M., Hoque A.T., Moskaluk C.A., da Costa L.T., Rozenblum E., Weinstein C.L., Fischer A., Yeo C.J., Hruban R.H., Kern S.E. DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science. 271:1996;350-353.
21. Lagna G., Hata A., Hemmati-Brivanlou A., Massague J. Partnership between DPC4 and Smad proteins in TGF-β signalling pathways. Nature. 383:1996;832-836.
22. Macias-Silva M., Abdollah S., Hoodless P.A., Pirone R., Attisano L., Wrana J.L. MADR2 is a substrate of the TGF-β receptor and its phosphorylation is required for nuclear accumulation and signaling. Cell. 87:1996;1215-1224.
23. Kretzschmar M., Liu F., Hata A., Goody J., Massague J. The TGF-β family mediator Smad1 is phosphorylated directly and activated functionally by the BMP receptor kinase. Genes & Dev. 11:1997;984-995.
24. Baker J.C., Harland R.M. From receptor to nucleus: the Smad pathway. Curr. Opin. in Genet. Dev. 7:1997;467-473.
25. Heldin C.H., Miyazono K., ten Dijke P. TGF-β signaling from cell membrane to nucleus through Smad proteins. Nature. 390:1997;465-471.
26. Zhang Y., Derynck R. Regulation of Smad signaling by protein association and signalling crosstalk. Trends in Cell Biology. 9:1999;274-279.
27. Hata A., Lo R.S., Wotton D., Lagna G., Massague J. Mutations increasing autoinhibition inactivate tumour suppressors Smad2 and Smad4. Nature. 388:1997;82-87.
28. Imamura T., Takase M., Nishihara A., Oeda E., Hanai J., Kawabata M., Miyazono K. Smad6 inhibits signalling by the TGF-β superfamily. Nature. 389:1997;622-626.
29. Nakao A., Afrakhte M., Moren A., Nakayama T., Christian J.L., Heuchel R., Itoh S., Kawabata M., Heldin N.E., Heldin C.H., ten Dijke P. Identification of Smad7, a TGF-β-inducible antagonist of TGF-β signaling. Nature. 389:1997;631-635.
30. Hata A., Lagna G., Massague J., Hemmati-Brivanlou A. Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor. Genes & Dev. 12:1998;186-197.
31. Chen Y., Lebrun J.J., Vale W. Regulation of transforming growth factor-β- and activin-induced transcription by mammalian Mad proteins. Proc. Natl. Acad. Sci. USA. 93:1996;12992-12997.
32. Yingling J.M., Datto M.B., Wong C., Frederick J.P., Liberati N.T., Wang X.-F. The tumor suppressor Smad4 is a transforming growth factor β-inducible DNA binding protein. Mol. Cell Biol. 17:1997;7019-7028.
33. Zawel L., Dai J.L., Buckhaults P., Zhou S., Kinzler K.W., Vogelstein B., Kern S.E. Human Smad3 and Smad4 are sequence-specific transcription activators. Mol. Cell. 1:1998;611-618.
34. Kim J., Johnson K., Chen H.J., Carroll S., Laughon A. Drosophila Mad binds to DNA and directly mediate activation of vestigial by Decapentaplegic. Nature. 388:1997;304-308.
35. Xu X., Yin Z., Hudson J.B., Ferguson E.L., Frasch M. Smad proteins act in combination with synergistic and antagonistic regulators to target Dpp responses to the Drosophila mesoderm. Genes & Dev. 12:1998;2354-2370.
36. Szuts D., Eresh S., Bienz M. Functional intertwining of Dpp and EGFR signaling during Drosophila endoderm induction. Genes & Dev. 12:1998;2022-2035.
37. Dennler S., Itoh S., Vivien D., ten Dijke P., Huet S., Gauthier J.M. Direct binding of Smad3 and Smad4 to critical TGF-β-inducible elements in the promoter of human plasminogen activator inhibitor-type 1 gene. EMBO J. 17:1998;3091-3100.
38. Song C.Z., Siok T.E., Gelehrter T.D. Smad4/DPC4 and Smad3 mediate transforming growth factor-β (TGF-β) signaling through direct binding to a novel TGF-β-responsive element in the human plasminogen activator inhibitor-1 promoter. J. Biol. Chem. 273:1998;29287-29290.
39. Stroschein S.L., Wang W., Luo K. Cooperative binding of Smad proteins to two adjacent DNA elements in the plasminogen activator inhibitor-1 promoter mediates transforming growth factor β-induced smad-dependent transcriptional activation. J. Biol. Chem. 274:1999;9431-9441.
40. Hua X., Liu X., Ansari D.O., 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.
41. Chen S.J., Yuan W., Mori Y., Levenson A., Trojanowska M., Varga J. Stimulation of type I collagen transcription in human skin fibroblasts by TGF-β: involvement of Smad 3. J. Invest. Dermatol. 112:1999;49-57.
42. Vindevoghel L., Kon A., Lechleider R.J., Uitto J., Roberts A.B., Mauviel A. Smad-dependent transcriptional activation of human type VII collagen gene (COL7A1) promoter by transforming growth factor-β J. Biol. Chem. 273:1998;13053-13057.
43. Wong C., Rougier-Chapman E.M., Frederick J.P., Datto M.B., Liberati N.T., Li J.M., Wang X.-F. Smad3-Smad4 and AP-1 complexes synergize in transcriptional activation of the c-Jun promoter by transforming growth factor-β Mol. Cell Biol. 19:1999;1821-1830.
44. Jonk L.J., Itoh S., Heldin C.H., ten Dijke P., Kruijer W. Identification and functional characterization of a Smad binding element [SBE] in the JunB promoter that acts as a transforming growth factor-β, activin, bone morphogenetic protein-inducible enhancer. J. Biol. Chem. 273:1998;21145-21152.
45. Dennler S., Huet S., Gauthier J.M. A short amino-acid sequence in MH1 domain is responsible for functional differences between Smad2 and Smad3. Oncogene. 18:1999;1643-1648.
46. Yagi K., Goto D., Hamamoto T., Takenoshita S., Kato M., Miyazono K. Alternatively spliced variant of Smad2 lacking exon 3. Comparison with wild-type Smad2 and Smad3. J. Biol. Chem. 274:1999;703-709.
47. Chen X., Rubock M.J., Whitman M. A transcriptional partner for MAD proteins in TGF-β signaling. Nature. 383:1996;691-696.
48. Chen X., Weisberg E., Fridmacher V., Watanabe M., Naco G., Whitman M. Smad4 and FAST-1 in the assembly of activin-responsive factor. Nature. 389:1997;85-89.
49. Liu F., Pouponnot C., Massague J. Dual role of the Smad4/DPC4 tumor suppressor in TGF-β inducible transcriptional complexes. Genes & Dev. 11:1997;3157-3167.
50. Liu B., Dou C.L., Prabhu L., Lai E. FAST-2 is a mammalian winged-helix protein which mediates transforming growth factor β signals. Mol. Cell Biol. 19:1999;424-430.
51. Labbe E., Silvestri C., Hoodless P.A., Wrana J.L., Attisano L. Smad2 and Smad3 positively and negatively regulate TGF-β-dependent transcription through the forkhead DNA-binding protein FAST2. Mol. Cell. 2:1998;109-120.
52. Nagarajan R.P., Liu J., 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.
53. Zhou S., Zawel L., Lengauer C., Kinzler K.W. Vogelstein B Characterization of human FAST-1, a TGF-β and activin signal transducer. Mol. Cell. 2:1998;121-127.
54. Liberati N.T., Datto M.B., Frederick J.P., Shen X., Wong C., Rougier-Chapman E.M., Wang X.-F. Smads bind directly to the Jun family of AP-1 transcription factors. Proc. Natl. Acad. Sci. USA. 96:1999;4844-4849.
55. Zhang Y., Feng X.H., Derynck R. Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-β-induced transcription. Nature. 394:1998;909-913.
56. Yanagisawa J., Yanagi Y., Masuhiro Y., Suzawa M., Watanabe M., Kashiwagi K., Toriyabe T., Kawabata M., Miyazono K., Kato S. Convergence of transforming growth factor-β and vitamin D signaling pathways on Smad transcriptional coactivators. Science. 283:1999;1317-1321.
57. Song C.Z., Tian X., Gelehrter T.D. Glucocorticoid receptor inhibits transforming growth factor-β signaling by directly targeting the transcriptional activation function of Smad3. Proc. Natl. Acad. Sci. USA. 96:1999;11776-11781.
58. Sano Y., Harada J., Tashiro S., Gotoh-Mandeville R., Maekawa T., Ishii S. ATF-2 is a common nuclear target of Smad and TAK1 pathways in transforming growth factor-β signaling. J. Biol. Chem. 274:1999;8949-8957.
59. Kurokawa M., Mitani K., Irie K., Matsuyama T., Takahashi T., Chiba S., Yuzaki Y., Matsumoto K., Hirai H. The oncoprotein Evi-1 represses TGF-β signalling by inhibiting Smad3. Nature. 394:1998;92-96.
60. 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., 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.
61. Wu Y., Haugen J.D., Zinsmeister A.R., Kumar R. 1α25-dihydroxyvitamin D3 increases transforming growth factor and transforming growth factor receptor type I and II synthesis in human bone cells. Biochem. Biophys. Res. Com. 239:1997;734-739.
62. Liu P., Oyajobi B.O., Russell R.G., Scutt A. Regulation of osteogenic differentiation of human bone marrow stromal cells: interaction between transforming growth factor-β and 1,25(OH) vitamin D(3) In vitro. Calcif. Tissue Int. 65:1999;173-180.
63. Staal A., Van Wijnen A.J., Desai R.K., Pols H.A., Birkenhager J.C., Deluca H.F., Denhardt D.T., Stein J.L., Van Leeuwen J.P., Stein G.S., Lian J.B. Antagonistic effects of transforming growth factor-β on vitamin D3 enhancement of osteocalcin and osteopontin transcription: reduced interactions of vitamin D receptor/retinoid X receptor complexes with vitamin E response elements. Endocrinology. 137:1996;2001-2011.
64. Feng X.H., Zhang Y., Wu R.Y., Derynck 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.
65. Nishihara A., Hanai J.I., Okamoto N., Yanagisawa J., Kato S., Miyazono K., Kawabata M. Role of p300, a transcriptional coactivator, in signalling of TGF-β Genes Cells. 3:1998;613-623.
66. Shen X., Hu P.P., Liberati N.T., Datto M.B., Frederick J.P., Wang X.-F. TGF-β-induced phosphorylation of Smad3 regulates its interaction with the coactivator p300/CREB-binding protein. Mol. Biol. Cell. 9:1998;3309-3319.
67. Pouponnot C., Jayaraman L., Massague J. Physical and functional interaction of Smads and p300/CBP. J. Biol. Chem. 273:1998;22865-22868.
68. Nakashima K., Yanagisawa M., Arakawa H., Kimura N., Hisatsune T., Kawabata M., Miyazono K., Taga T. Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300. Science. 284:1999;479-482.
69. Stroschein S.L., Wang W., Zhou S., Zhou Q., Luo K. Negative feedback regulation of TGF-β signaling by the SnoN oncoprotein. Science. 286:1999;771-774.
70. Sun Y., Liu X., Ng Eaton E., Lane W.S., Lodish H.F., Weinberg R.A. Interaction of the Ski oncoprotein with Smad3 regulated TGF-β signaling. Mol. Cell. 4:1999;1-20.
71. Luo K., Stroschein S., Wang W., Chen D., Martens E., Zhou S., Zhou Q. The Ski oncoprotein interacts with the Smad proteins to repress TGF-β signaling. Genes & Dev. 13:1999;2196-2206.
72. Wotton D., Lo R.S., Lee S., Massague J. A Smad transcriptional corepressor. Cell. 97:1999;29-39.
73. Datto M.B., Frederick J.P., Pan L., Borton A.J., Zhuang Y., Wang X.-F. Targeted disruption of Smad3 reveals an essential role in transforming growth factor-β-mediated signal transduction. Mol. Cell Biol. 19:1999;2495-2504.
74. Yang X., Letteria J.J., Lechleider R.J., Chen L., Hayman R., Gu H., Roberts A.B., Deng C. Targeted disruption of Smad3 results in impaired mucosal immunity and diminished T cell responsivness to TGF-β EMBO J. 18:1999;1280-1291.
75. Zhu Y., Richardson J.A., Parada J.M. Smad3 mutant mice develop metastatic colorectal cancer. Cell. 94:1998;703-714.
76. Sirard C., de la Pompa J.L., Elia A., Itie A., Mirtsos C., Cheung A., Hahn S., Wakeham A., Schwartz L., Kern S.E., Rossant J., Mak T.W. The tumor suppressor gene Smad4/Dpc4 is required for gastrulation and later for anterior development of the mouse embryo. Genes & Dev. 12:1998;107-119.
77. Weinstein M., Yang X., Li C., Xu X., Gotay J., Deng C.X. Failure of egg cylinder elongation and mesoderm induction in mouse embryos lacking the tumor suppressor Smad2. Proc. Natl. Acad. Sci. USA. 95:1998;9378-9383.
78. Nomura M., Li E. Smad2 role in mesoderm formation, left-right patterning and craniofacial development. Nature. 393:1998;786-790.
79. Waldrip W.R., Bikoff E.K., Hoodless P.A., Wrana J.L., Robertson E.J. Smad2 signaling in extraembryonic tissues determines anterior-posterior polarity of the early mouse embryo. Cell. 92:1998;797-808.
80. Yang X., Castilla L.H., Xu X., Li C., Gotay J., Weinstein M., Liu P.P., Deng C.X. Angiogenesis defects and mesenchymal apoptosis in mice lacking Smad5. Development. 126:1999;1571-1580.
81. Bottinger E.P., Letterio J.J., Roberts A.B. Biology of TGF-β in knockout and transgenic mouse models. Kidney Int. 51:1997;1355-1360.
82. Kaartinen V., Voncken J.W., Shuler C., Warburton D., Bu D., Heisterkamp N., Groffen J. Abnormal lung development and cleft palate in mice lacking TGF-β3 indicates defects of epithelial-mesenchymal interaction. Nat. Genet. 4:1995;415-421.
83. Sanford L.P., Ormsby I., Gittenberger-de Groot A.C., Sariola H., Friedman R., Boivin G.P., Cardell E.L., Doetschman T. TGFβ2 knockout mice have multiple developmental defects that are non-overlapping with other TGFβ knockout phenotypes. Development. 13:1997;2659-2670.
84. Oshima M., Oshima H., Taketo M.M. TGF-β receptor type II deficiency results in defects of yolk sac hematopoiesis and vasculogenesis. Dev. Biol. 179:1996;297-302.
85. Rich JN, Zhang M, Datto MB, Bigner DD, Wang X-F. Transforming growth factor-β-mediated p15 induction and growth inhibition in astrocytes is Smad3-dependent and a pathway prominently altered in human glioma cell lines. J Biol Chem (in press)
86. Ashcroft G.S., Yang X., Glick A.B., Weinstein M., Letterio J.J., Mizel D.E., Anzano M., Greenwell-Wild T., Wahl S.M., Deng C., Roberts A.B. Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response. Nature Cell Biol. 1:1999;260-266.
87. Wang XF, Datto MB, Liberati NT, Bornt AJ, Fredrick JP. Unpublished observations 1999
88. Datto M.B., Yu Y., Wang X.-F. Functional analysis of the transforming growth factor β responsive elements in the WAF1/Cip1/p21 promoter. J. Biol. Chem. 270:1995;28623-28628.
89. Li J.-M., Nichols M.A., Chandrasekharan S., Xiong Y., Wang X.-F. Transforming growth factor β activates the promoter of cyclin-dependent kinase inhibitor p15INK4B through an Sp1 consensus site. J. Biol. Chem. 270:1995;26750-26753.
90. Moustakas A., Kardassis D. Regulation of the human p21/WAF1/Cip1 promoter in hepatic cells by functional interactions between Sp1 and Smad family members. Proc. Natl. Acad. Sci. USA. 95:1998;6733-6738.
91. Zhou S., Buckhaults P., Zawel L., Bunz F., Riggins G., Dai J.L., Kern S.E., Kinzler K.W., Vogelstein B. Targeted deletion of Smad4 shows it is required for transforming growth factor β and activin signaling in colorectal cancer cells. Proc. Natl. Acad. Sci. USA. 95:1998;2412-2416.
92. Dai J.L., Schutte M., Bansal R.K., Wilentz R.E., Sugar A.Y., Kern S.E. Transforming growth factor-β responsiveness in DPC4/SMAD4-null cancer cells. Mol. Carcinog. 26:1999;37-43.
93. Kulkarni A.B., Huh C.G., Becker D., Geiser A., Lyght M., Flanders K.C., Roberts A.B., Sporn M.B., Ward J.M., Karlsson S. Transforming growth factor β1 null mutation in mice causes excessive inflammatory response and early death. Proc. Natl. Acad. Sci. USA. 90:1993;770-774.
94. Shull M.M., Ormsby I., Kier A.B., Pawlowski S., Diebold R.J., Yin M., Allen R., Sidman C., Proetzel G., Calvin D. Targeted disruption of the mouse transforming growth factor-β 1 gene results in multifocal inflammatory disease. Nature. 359:1992;693-699.
95. Kulkarni A.B., Karlsson S. Inflammation and TGF-β1: lessons from the TGF-β1 null mouse. Res. Immunol. 148:1997;453-456.
96. Li Y.C., Pirro A.E., Amling M., Delling G., Baron R., Bronson R., Demay M.B. Targeted ablation of the vitamin D receptor: an animal model of vitamin D-dependent rickets type II with alopecia. Proc. Natl. Acad. Sci. USA. 94:1997;9831-9835.
97. Yoshizawa T., Handa Y., Uematsu Y., Takeda S., Sekine K., Yoshihara Y., Kawakami T., Arioka K., Sato H., Uchiyama Y., Masushige S., Fukamizu A., Matsumoto T., Kato S. Mice lacking the vitamin D receptor exhibit impaired bone formation, uterine hypoplasia and growth retardation after weaning. Nat. Genet. 16:1997;391-396.
98. Noda M., Camilliere J.J. In vivo stimulation of bone formation by transforming growth factor-β Endocrinology. 124:1989;2991-2994.
99. Marcelli C., Yates A.J., Munday G.R. In vivo effects of human recombinant transforming growth factor β on bone turnover in normal mice. J. Bone Min. Res. 5:1990;1087-1096.
100. Robey P.G., Young M.F., Flanders K.C., Roche N.S., Kondaiah P., Reddi A.H., Termine J.D., Sporn M.B., Roberts A.B. Osteoblasts synthesize and respond to transforming growth factor-type β (TGF-β) in Vitro. J. Cell Biol. 105:1987;457-463.
101. Centrella M., McCarthy T.L., Canalis E. Transforming growth factor β is a bifunctional regulator of replication and collagen synthesis in osteoblast-enriched cell cultures from fetal rat bone. J. Biol. Chem. 262:1987;2869-2874.
102. Pfeilschifter J., Wolf O., Naumann A., Minne H.W., Mundy G.R., Ziegler R. Chemotactic Response of osteoblastlike cells to transforming growth factor-β J. Bone and Mineral. Res. 5:1990;825-829.
103. Takai H., Kanematsu M., Yano K., Tsuda E., Higashio K., Ikeda K., Watanabe K., Yamada Y. Transforming growth factor-β stimulates the production of osteoprotegerin/osteoclastogenesis inhibitory factor by bone marrow stromal cells. J. Biol. Chem. 273:1998;27091-27096.
104. Breen E.C., Ignotz R.A., McCabe L., Stein J.L., Stein G.S., Lian J.B. TGF-β alters growth and differentiation related gene expression in proliferating osteoblasts in vitro, preventing development of the mature bone phenotype. J. Cell Phys. 160:1994;323-335.
105. Serra R., Johnson M., Filvaroff E.H., LaBorde J., Sheehan D.M., Derynck R., Moses H.L. Expression of truncated, kinase-defective TGF-β type II receptor in mouse skeletal tissue promotes terminal chondrocyte differentiation and osteroarthritis. J. Cell Biol. 139:1997;541-552.
106. Riggins G.J., Kinzler K.W., Vogelstein B., Thiagalingam S. Frequency of Smad gene mutations in human cancers. Cancer Res. 57:1997;2578-2580.
107. Howe J.R., Roth S., Ringold J.C., Summers R.W., Jarvinen H.J., Sistonen P., Tomlinson I.P., Houlston R.S., Bevan S., Mitros F.A., Stone E.M., Aaltonen L.A. Mutations in the SMAD4/DPC4 gene in juvenile polyposis. Science. 280:1998;1086-1088.
108. Takaku K., Oshima M., Miyoshi H., Matsui M., Seldin M.F., Taketo M.M. Intestinal tumorigenesis in compound mutant mice of both Dpc4 [Smad4] and Apc genes. Cell. 92:1998;645-656.
109. Pennisi E. How a growth control path takes a wrong turn to cancer. Science. 281:1998;1438-1439.
110. Oshima M., Oshima H., Kitagawa K., Kobayashi M., Itakura C., Taketo M. Loss of Apc heterozygosity and abnormal tissue building in nascent intestinal polyps in mice carrying a truncated Apc gene. Proc. Natl. Acad. Sci. USA. 92:1997;4482-4486.