Specificity and versatility in TGF-β signaling through smads

Annual Review of Cell and Developmental Biology

Volumn 21, Issue , 2005, Pages 659-693

  Feng, Xin Hua ^a   Derynck, Rik ^b  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Bone morphogenetic protein; Complexity; Signal transduction; TGF receptor; Transcription

Indexed keywords

BONE MORPHOGENETIC PROTEIN; DNA BINDING PROTEIN; LIGAND; PROTEIN SERINE THREONINE KINASE; SMAD PROTEIN; TRANSCRIPTION FACTOR; TRANSFORMING GROWTH FACTOR BETA;

AMINO ACID SEQUENCE; CELL NUCLEUS; ENZYME SUBSTRATE COMPLEX; GENE EXPRESSION REGULATION; GENOME; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; PROTEIN TRANSPORT; REVIEW; SIGNAL TRANSDUCTION; TRANSCRIPTION INITIATION; TRANSCRIPTION REGULATION; VERTEBRATE;

ANIMALS; BONE MORPHOGENETIC PROTEIN RECEPTORS; FORECASTING; HUMANS; LIGANDS; MODELS, BIOLOGICAL; RECEPTORS, TRANSFORMING GROWTH FACTOR BETA; SENSITIVITY AND SPECIFICITY; SIGNAL TRANSDUCTION; SMAD PROTEINS; TRANS-ACTIVATION (GENETICS); TRANSCRIPTION, GENETIC; TRANSFORMING GROWTH FACTOR BETA;

VERTEBRATA;

EID: 23044466047     PISSN: 10810706     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev.cellbio.21.022404.142018     Document Type: Review

References (203)

1. Abdel-Wahab N, Wicks SJ, Mason RM, Chantry A. 2002. Decorin suppresses transforming growth factor-β-induced expression of plasminogen activator inhibitor-1 in human mesangial cells through a mechanism that involves Ca2+-dependent phosphorylation of Smad2 at serine-240. Biochem. J. 362:643-49
2. Alliston T, Choy L, Ducy P, Karsenty G, Derynck R. 2001. TGF-β-induced repression of CBFA1 by Smad3 decreases cbfa1 and osteocalcin expression and inhibits osteoblast differentiation. EMBO J. 20:2254-72
3. Alliston T, Ko TC, Cao Y, Liang Y-Y, Feng X-H, Chang C, Derynck R. 2005. Repression of BMP- and activin-inducible transcription by Evi-1. J. Biol. Chem. 280:24227-37
4. Annes JP, Munger JS, Rifkin DB. 2003. Making sense of latent TGFβ activation. J. Cell Sci. 116:217-24
5. Bai RY, Koester C, Ouyang T, Hahn SA, Hammerschmidt M, et al. 2002. SMIF, a Smad4-interacting protein that functions as a co-activator in TGFβ signalling. Nat. Cell Biol. 4:181-90
6. Bai S, Cao X. 2002. A nuclear antagonistic mechanism of inhibitory Smads in transforming growth factor-β signaling. J. Biol. Chem. 277:4176-82
7. Bai S, Shi X, Yang X, Cao X. 2000. Smad6 as a transcriptional corepressor. J. Biol. Chem. 275:8267-70
8. Benchabane H, Wrana JL. 2003. GATA- and Smad1-dependent enhancers in the Smad7 gene differentially interpret bone morphogenetic protein concentrations. Mol. Cell Biol. 23:6646-61
9. Bitzer M, von Gersdorff G, Liang D, Dominguez-Rosales A, Beg AA, et al. 2000. A mechanism of suppression of TGF-β/SMAD signaling by NF-κB/RelA. Genes Dev. 14:187-97
10. Blobe GC, Liu X, Fang SJ, How T, Lodish HF. 2001. A novel mechanism for regulating transforming growth factor β (TGF-β) signaling. Functional modulation of type III TGF-β receptor expression through interaction with the PDZ domain protein, GIPC. J. Biol. Chem. 276:39608-17
11. Blokzijl A, Dahlqvist C, Reissmann E, Falk A, Moliner A, et al. 2003. Cross-talk between the Notch and TGF-β signaling pathways mediated by interaction of the Notch intracellular domain with Smad3. J. Cell Biol. 163:723-28
12. Blokzijl A, ten Dijke P, Ibanez CF. 2002. Physical and functional interaction between GATA-3 and Smad3 allows TGF-β regulation of GATA target genes. Curr. Biol. 12:35-45
13. Boesen CC, Radaev S, Motyka SA, Patamawenu A, Sun PD. 2002. The 1.1 Å crystal structure of human TGF-β type II receptor ligand binding domain. Structure 10:913-19
14. Brodin G, Ahgren A, ten Dijke P, Heldin CH, Heuchel R. 2000. Efficient TGF-β induction of the Smad7 gene requires cooperation between AP-1, Sp1, and Smad proteins on the mouse Smad7 promoter. J. Biol. Chem. 275:29023-30
15. Brown CO 3rd, Chi X, Garcia-Gras E, Shirai M, Feng XH, et al. 2004. The cardiac determination factor, Nkx2-5, is activated by mutual cofactors GATA-4 and Smad1/4 via a novel upstream enhancer. J. Biol. Chem. 279:10659-69
16. Brown JD, DiChiara MR, Anderson KR, Gimbrone MA Jr, Topper JN 1999. MEKK-1, a component of the stress (stress-activated protein kinase/c-Jun N-terminal kinase) pathway, can selectively activate Smad2-mediated transcriptional activation in endothelial cells. J. Biol. Chem. 274:8797-805
17. Chacko BM, Qin B, Correia JJ, Lam SS, de Caestecker MP, et al. 2001. The L3 loop and C-terminal phosphorylation jointly define Smad protein trimerization. Nat. Struct. Biol. 8:248-53
18. Chacko BM, Qin BY, Tiwari A, Shi G, Lam S, et al. 2004. Structural basis of heteromeric Smad protein assembly in TGF-β signaling. Mol. Cell 15:813-23
19. Chen CR, Kang Y, Massagué J. 2001. Defective repression of c-myc in breast cancer cells: A loss at the core of the transforming growth factor β growth arrest program. Proc. Natl. Acad. Sci. USA 98:992-99
20. Chen CR, Kang Y, Siegel PM, Massagué J. 2002. E2F4/5 and p107 as Smad cofactors linking the TGFβ receptor to c-myc repression. Cell 110:19-32
21. Chen D, Ji X, Harris MA, Feng JQ, Karsenty G, et al. 1998. Differential roles for bone morphogenetic protein (BMP) receptor type IB and IA in differentiation and specification of mesenchymal precursor cells to osteoblast and adipocyte lineages. J. Cell Biol. 142:295-305
22. Chen W, Kirkbride KC, How T, Nelson CD, Mo J, et al. 2003. β-arrestin 2 mediates endocytosis of type III TGF-β receptor and down-regulation of its signaling. Science 301:1394-97
23. Chen X, Weisberg E, Fridmacher V, Watanabe M, Naco G, et al. 1997. Smad4 and FAST-1 in the assembly of activin-responsive factor. Nature 389:85-89
24. Chen YG, Hata A, Lo RS, Wotton D, Shi Y, et al. 1998. Determinants of specificity in TGF-β signal transduction. Genes Dev. 12:2144-52
25. Chen YG, Massagué J. 1999. Smad1 recognition and activation by the ALK1 group of transforming growth factor-jo family receptors. J. Biol. Chem. 274:3672-77
26. Chiba S, Takeshita K, Imai Y, Kumano K, Kurokawa M, et al. 2003. Homeoprotein DLX-1 interacts with Smad4 and blocks a signaling pathway from activin A in hematopoietic cells. Proc. Natl. Acad. Sci. USA 100:15577-82
27. ChipukJE, Cornelius SC, Pultz NJ, Jörgensen JS, Bonham MJ, et al. 2002. The androgen receptor represses transforming growth factor-β signaling through interaction with Smad3. J. Biol. Chem. 277:1240-48
28. Chou WC, Prokova V, Shiraishi K, Valcourt U, Moustakas A, et al. 2003. Mechanism of a transcriptional cross talk between transforming growth factor-β-regulated Smad3 and Smad4 proteins and orphan nuclear receptor hepatocyte nuclear factor-4. Mol. Biol. Cell 14:1279-94
29. Choy L, Derynck R. 2003. Transforming growth factor-β inhibits adipocyte differentiation by Smad3 interacting with CCAAT/enhancer-binding protein (C/EBP) and repressing C/EBP transactivation function. J. Biol. Chem. 278:9609-19
30. Comijn J, Berx G, Vermassen P, Verschueren K, van Grunsven L, et al. 2001. The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Mol. Cell 7:1267-78
31. Conery AR, Cao Y, Thompson EA, Townsend CM Jr, Ko TC, et al. 2004. Akt interacts directly with Smad3 to regulate the sensitivity to TGF-β induced apoptosis. Nat. Cell Biol. 6:366-72
32. Cordenonsi M, Dupont S, Maretto S, Insinga A, Imbriano C, et al. 2003. Links between tumor suppressors: p53 is required for TGF-β gene responses by cooperating with Smads. Cell 113:301-14
33. Costamagna E, Garcia B, Santisteban P. 2003. The functional interaction between the paired domain transcription factor Pax8 and Smad3 is involved in the transforming growth factor-β repression of the sodium/iodide symporter gene. J. Biol. Chem. 279:3439-46
34. Coyle-Rink J, Sweet T, Abraham S, Sawaya B, Batuman O, et al. 2002. Interaction between TGFβ signaling proteins and C/EBP controls basal and Tat-mediated transcription of HIV-1 LTR in astrocytes. Virology 299:240-47
35. Dahlqvist C, Blokzijl A, Chapman G, FalkA, Dannaeus K, et al. 2003. Functional Notch signaling is required for BMP4-induced inhibition of myogenic differentiation. Development 130:6089-99
36. Dai H, Hogan C, Gopalakrishnan B, Torres-Vazquez J, Nguyen M, et al. 2000. The zinc finger protein schnurri acts as a Smad partner in mediating the transcriptional response to decapentaplegic. Dev. Biol. 227:373-87
37. Datta PK, Moses HL. 2000. STRAP and Smad7 synergize in the inhibition of transforming growth factor β signaling. Mol. Cell Biol. 20:3157-67
38. de Caestecker M, Parks W, Frank C, Castagnino P, Bottaro D, et al. 1998. Smad2 transduces common signals from receptor serine-threonine and tyrosine kinases. Genes Dev. 12:1587-92
39. de Caestecker MP, Yahata T, Wang D, Parks WT, Huang S, et al. 2000. The Smad4 activation domain (SAD) is a proline-rich, p300-dependent transcriptional activation domain. J. Biol. Chem. 275:2115-22
40. del Re E, Babitt JL, Pirani A, Schneyer AL, Lin HY. 2004. In the absence of type III receptor, the transforming growth factor (TGF)-β type II receptor requires the type I receptor to bind TGF-β2.7. Biol. Chem. 279:22765-72
41. Derynck R, Zhang YE. 2003. Smad-dependent and Smad-independent pathways in TGF-β family signalling. Nature 425:577-84
42. Di Guglielmo GM, Le Roy C, Goodfellow AF, Wrana JL. 2003. Distinct endocytic pathways regulate TGF-β receptor signalling and turnover. Nat. Cell Biol. 5:410-21
43. Ebisawa T, Fukuchi M, Murakami G, Chiba T, Tanaka K, et al. 2001. Smurfl interacts with transforming growth factor-β type I receptor through Smad7 and induces receptor degradation. J. Biol. Chem. 276:12477-80
44. Engel ME, McDonnell MA, Law BK, Moses HL. 1999. Interdependent SMAD and JNK signaling in transforming growth factor-β-mediated transcription. J. Biol. Chem. 274:37413-20
45. Feng X-H, Derynck R. 1997. A kinase subdomain of transforming growth factor-β (TGF-β) type I receptor determines the TGF-β intracellular signaling specificity. EMBO J. 16:3912-23
46. Ink4B. Mol. Cell 9:133-43
47. Ink4B transcription in response to TGF-β. EMBO J. 19:5178-93
48. Feng X-H, Zhang Y, Wu R-Y, Derynck R. 1998. The tumor suppressor Smad4/DPC4 and transcriptional adaptor CBP/p300 are coactivators for Smad3 in TGF-β-induced transcriptional activation. Genes Dev. 12:2153-63
49. Frederick JP, Liberati NT, Waddell DS, Shi Y, Wang XF. 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. 24:2546-59
50. Furuhashi M, Yagi K, Yamamoto H, Furukawa Y, Shimada S, et al. 2001. Axin facilitates Smad3 activation in the transforming growth factor β signaling pathway. Mol. Cell Biol. 21:5132-41
51. Germain S, Howell M, Esslemont GM, Hill CS. 2000. Homeodomain and winged-helix transcription factors recruit activated Smads to distinct promoter elements via a common Smad interaction motif. Genes Dev. 14:435-51
52. Goumans MJ, Valdimarsdottir G, Itoh S, Lebrin F, Larsson J, et al. 2003. Activin receptor-like kinase (ALK)1 is an antagonistic mediator of lateral TGFβ/ALK5 signaling. Mol. Cell 12:817-28
53. Goumans MJ, Valdimarsdottir G, Itoh S, Rosendahl A, Sideras P, et al. 2002. Balancing the activation state of the endothelium via two distinct TGF-β type I receptors. EMBO J. 21:1743-53
54. Greenwald J, Groppe J, Gray P, Wiater E, Kwiatkowski W, et al. 2003. The BMP7/ActRII extracellular domain complex provides new insights into the cooperative nature of receptor assembly. Mol. Cell 11:605-17
55. Greenwald J, Vega ME, Allendorph GP, Fischer WH, Vale W, et al. 2004. A flexible activin explains the membrane-dependent cooperative assembly of TGF-jS family receptors. Mol. Cell 15:485-89
56. Grinberg AV, Kerppola T. 2003. Both Max and TFE3 cooperate with Smad proteins to bind the plasminogen activator inhibitor-1 promoter, but they have opposite effects on transcriptional activity. J. Biol. Chem. 278:11227-36
57. Grönroos E, Hellman U, Heldin CH, Ericsson J. 2002. Control of Smad7 stability by competition between acetylation and ubiquitination. Mol. Cell 10:483-93
58. Hanai J, Chen LF, Kanno T, Ohtani-Fujita N, Kim WY, et al. 1999. Interaction and functional cooperation of PEBP2/CBF with Smads. Synergistic induction of the immunoglobulin germline Cα promoter. J. Biol. Chem. 274:31577-82
59. Hanyu A, Ishidou Y, Ebisawa T, Shimanuki T, Imamura T, et al. 2001. The N domain of Smad7 is essential for specific inhibition of transforming growth factor-β signaling. J. Cell Biol. 155:1017-27
60. Hart PJ, Deep S, Taylor AB, Shu Z, Hinck CS, et al. 2002. Crystal structure of the human TβR2 ectodomain-TGF-β3 complex. Nat. Struct. Biol. 9:203-8
61. Hata A, Lagna G, Massagué J, Hemmati-Brivanlou A. 1998. Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor. Genes Dev. 12:186-97
62. Hata A, Seoane J, Lagna G, Montalvo E, Hemmati-Brivanlou A, et al. 2000. OAZ uses distinct DNA- and protein-binding zinc fingers in separate BMP-Smad and Olf signaling pathways. Cell 100:229-40
63. Hayashi H, Abdollah S, Qiu Y, Gai J, Xu Y-Y, et al. 1997. The MAD-related protein Smad7 associates with the TGFβ receptor and functions as an antagonist of the TGFβ signaling. Cell 89:1165-73
64. Hayes S, Chawla A, Corvera S. 2002. TGF β receptor internalization into EEA1-enriched early endosomes: role in signaling to Smad2. J. Cell Biol. 158:1239-49
65. Hayes SA, Zarnegar M, Sharma M, Yang F, Peehl DM, et al. 2001. SMAD3 represses androgen receptor-mediated transcription. Cancer Res. 61:2112-18
66. Higashi K, Inagaki Y, Fujimori K, Nakao A, Kaneko H, Nakatsuka I. 2003. Inteferon-γ interferes with transforming growth factor-β signaling through direct interaction of YB-1 with Smad3. J. Biol. Chem. 278:43470-79
67. Hocevar BA, Smine A, Xu XX, Howe PH. 2001. The adaptor molecule Disabled-2 links the transforming growth factor β receptors to the Smad pathway. EMBO J. 20:2789-801
68. Hoodless PA, Pye M, Chazaud G, Labbé E, Attisano L, et al. 2001. FoxH1 (Fast) functions to specify the anterior primitive streak in the mouse. Genes Dev. 15:1257-71
69. Hu MC, Rosenblum ND. 2005. Smad1, β-catenin and TCF4 associate in a molecular complex with the Myc promoter in dysplastic renal tissue and cooperate to control Myc transcription. Development 132:215-25
70. Hua X, Miller ZA, Benchabane H, WranaJL, Lodish HF. 2000. Synergism between transcription factors TFE3 and Smad3 in TGF-β-induced transcription of the Smad7 gene. J. Biol. Chem. 275:33205-8
71. Hua X, Miller ZA, Wu G, Shi Y, Lodish HF. 1999. Specificity 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 96:13130-35
72. Huse M, Muir TW, Xu L, Chen YG, Kuriyan J, et al. 2001. The TGF β receptor activation process: an inhibitor-to-substrate-binding switch. Mol. Cell 8:671-82
73. Hussein SM, Duff EK, Sirard C. 2003. Smad4 and β-catenin co-activators functionally interact with lymphoid-enhancing factor to regulate graded expression of Msx2. J. Biol. Chem. 278:48805-14
74. Imamura T, Takase M, Nishihara A, Oeda E, Hanai J, et al. 1997. Smado inhibits signalling by the TGF-β superfamily. Nature 389:622-26
75. Inman GJ, Hill CS. 2002. Stoichiometry of active Smad-transcription factor complexes on DNA. J. Biol. Chem. 277:51008-16
76. Ishida W, Hamamoto T, Kusanagi K, Yagi K, Kawabata M, et al. 2000. Smado is a Smad1/5-induced Smad inhibitor. Characterization of bone morphogenetic protein-responsive element in the mouse Smado promoter. J. Biol. Chem. 275:6075-79
77. Itoh F, Itoh S, Goumans MJ, Valdimarsdottir G, Iso T, et al. 2004. Synergy and antagonism between Notch and BMP receptor signaling pathways in endothelial cells. EMBO J. 23:541-51
78. Itoh S, Ericsson J, Nishikawa J, Heldin CH, ten Dijke P. 2000. The transcriptional co-activator P/CAF potentiates TGF-β/Smad signaling. Nucleic Acids Res. 28:4291-98
79. Izutsu K, Kurokawa M, Imai Y, Maki K, Mitani K, et al. 2001. The corepressor CtBP interacts with Evi-1 to repress transforming growth factor β signaling. Blood 97:2815-22
80. Janda E, Lehmann K, Killisch I, Jechlinger M, Herzig M, et al. 2002. Ras and TGF-β cooperatively regulate epithelial cell plasticity and metastasis: dissection of Ras signaling pathways. J. Cell Biol. 156:299-313
81. Jayaraman L, Massagué J. 2000. Distinct oligomeric states of SMAD proteins in the transforming growth factor-β pathway. J. Biol. Chem. 275:40710-17
82. Kahata K, Hayashi M, Asaka M, Hellman U, Kitagawa H, et al. 2004. Regulation of transforming growth factor-β and bone morphogenetic protein signalling by transcriptional coactivator GCN5. Genes Cells 9:143-51
83. Kaji H, Chanaff L, Lebrun JJ, Goltzman D, Hendy GN. 2001. Inactivation ofmenin, a Smad3-interacting protein, blocks transforming growth factor type β signaling. Proc. Natl. Acad. Sci. USA 98:3837-42
84. Kang HY, Huang KE, Chang SY, Ma WL, Lin WJ, et al. 2002. Differential modulation of androgen receptor-mediated transactivation by Smad3 and tumor suppressor Smad4. J. Biol. Chem. 277:43749-56
85. Kang JS, Alliston T, Delston R, Derynck R. 2005. Repression of Runx2 function by TGF-β through recruitment of class II histone deacetylases by Smad3. EMBO J. In press
86. Kang Y, Chen CR, Massagué J. 2003. A self-enabling TGFβ response coupled to stress signaling: Smad engages stress response factor ATF3 for Id1 repression in epithelial cells. Mol. Cell 11:915-26
87. Kato Y, Habas R, Katsuyama Y, Naar AM, He X. 2002. A component of the ARC/Mediator complex required for TGF β/Nodal signalling. Nature 418:641-46
88. Kavsak P, Rasmussen RK, Causing CG, Bonni S, Zhu H, et al. 2000. Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF β receptor for degradation. Mol. Cell 6:1365-75
89. Kawata Y, Suzuki H, Higaki Y, Denisenko O, Schullery D, et al. 2002. bcn-1 element-dependent activation of the laminin γ1 chain gene by the cooperative action of transcription factor E3 (TFE3) and Smad proteins. J. Biol. Chem. 277:11375-84
90. Keller S, Nickel J, Zhang JL, Sebald W, Mueller TD. 2004. Molecular recognition of BMP-2 and BMP receptor IA. Nat. Struct. Mol. Biol. 11:481-88
91. Kim DW, Lassar AB. 2003. Smad-dependent recruitment of a histone deacetylase/Sin3A complex modulates the bone morphogenetic protein-dependent transcriptional repressor activity of Nkx3.2. Mol. Cell Biol. 23:8704-17
92. Kim J, Johnson K, Chen H, Carroll S, Laughon A. 1997. Drosophila Mad binds to DNA and directly mediates activation of vestigial by Decapentaplegic. Nature 388:304-8
93. Kim RH, Wang D, Tsang M, Martin J, Huff C, et al. 2000. A novel Smad nuclear interacting protein, SNIP1, suppresses p300-dependent TGF-β signal transduction. Genes Dev. 14:1605-16
94. Kirsch T, Sebald W, Dreyer MK. 2000. Crystal structure of the BMP-2-BRIA ectodomain complex. Nat. Struct. Biol. 7:492-96
95. Korchynskyi O, ten Dijke P. 2002. Identification and functional characterization of distinct critically important bone morphogenetic protein-specific response elements in the Id1 promoter. J. Biol. Chem. 277:4883-91
96. Kretzschmar M, Doody J, Massagué J. 1997. Opposing BMP and EGF signalling pathways converge on the TGF-β family mediator Smadl. Nature 389:618-22
97. Kretzschmar M, Doody J, Timokhina I, Massagué J. 1999. A mechanism of repression of TGFβ/Smad signaling by oncogenic Ras. Genes Dev. 13:804-16
98. Kurisaki K, Kurisaki A, Valcourt U, Terentiev AA, Pardali K, et al. 2003. Nuclear factor YY1 inhibits transforming growth factor β- and bone morphogenetic protein-induced cell differentiation. Mol. Cell Biol. 23:4494-510
99. Kurokawa M, Mitani K, Irie K, Matsuyama T, Takahashi T, et al. 1998. The oncoprotein Evi-1 represses TGF-β signalling by inhibiting Smad3. Nature 394:92-96
100. Kusanagi K, Inoue H, Ishidou Y, Mishima HK, Kawabata M, et al. 2000. Characterization of a bone morphogenetic protein-responsive Smad-binding element. Mol. Biol. Cell 11:555-65
101. Labbé E, Letamendia A, 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. USA 97:8358-63
102. Labbé E, Silvestri C, Hoodless PA, Wrana JL, Attisano L. 1998. Smad2 and Smad3 positively and negatively regulate TGF β-dependent transcription through the forkhead DNA-binding protein FAST2. Mol. Cell 2:109-20
103. Lagna G, Hemmati-Brivanlou A. 1999. A molecular basis for Smad specificity. Dev. Dyn. 214:269-77
104. Lebrin F, Goumans MJ, Jonker L, Carvalho RL, Valdimarsdottir G, et al. 2004. Endoglin promotes endothelial cell proliferation and TGF-β/ALK1 signal transduction. EMBO J. 23:4018-28
105. Lee KH, Evans S, Ruan TY, Lassar AB. 2004. SMAD-mediated modulation of YY1 activity regulates the BMP response and cardiac-specific expression of a GATA4/5/6-dependent chick Nkx2.5 enhancer. Development 131:4709-23
106. Lei S, Dubeykovskiy A, Chakladar A, Wojtukiewicz L, Wang TC. 2004. The murine gastrin promoter is synergistically activated by transforming growth factor-β/Smad and Wnt signaling pathways. J. Biol. Chem. 279:42492-502
107. Leong GM, Subramaniam N, Figueroa J, Flanagan JL, Hayman MJ, et al. 2001. Ski-interacting protein interacts with Smad proteins to augment transforming growth factor-β-dependent transcription. J. Biol. Chem. 276:18243-48
108. skP2. Mol. Cell Biol. 24:7524-37
109. Liberati NT, Datto MB, Frederick JP, Shen X, Wong C, et al. 1999. Smads bind directly to the Jun family of AP-1 transcription factors. Proc. Natl. Acad. Sci. USA 96:4844-49
110. Liberati NT, Moniwa M, Borton AJ, Davie JR, Wang XF. 2001. An essential role for Mad homology domain 1 in the association of Smad3 with histone deacetylase activity. J. Biol. Chem. 276:22595-603
111. Lin SY, Elledge SJ. 2003. Multiple tumor suppressor pathways negatively regulate telomerase. Cell 113:881-89
112. Lin X, Liang Y-Y, Sun B, Liang M, Brunicardi FC, et al. 2003. Smado recruits transcription corepressor CtBP to repress bone morphogenetic protein-induced transcription. Mol. Cell. Biol. 23:9081-93
113. Liu D, Black BL, Derynck R. 2001. TGF-β inhibits muscle differentiation through functional repression of myogenic transcription factors by Smad3. Genes Dev. 15:2950-66
114. Liu D, Kang JS, Derynck R. 2004. TGF-β-activated Smad3 represses MEF2-dependent transcription in myogenic differentiation. EMBO J. 23:1557-66
115. Liu F, Massagué J, Ruiz i Altaba A. 1998. Carboxy-terminally truncated GIi proteins associate with Smads. Nat. Genet. 20:325-26
116. Lo R, Chen Y-G, Shi Y, Pavletich NP, Massagué J. 1998. The L3 loop: a structural motif determining specific interactions between SMAD proteins and TGF-β receptors. EMBO J. 17:996-1005
117. López-Casillas F, Wrana JL, Massagué J. 1993. Betaglycan presents ligand to the TGFβ signaling receptor. Cell 73:1435-44
118. Lopez-Rovira T, Chalaux E, Rosa JL, Bartrons R, Ventura F. 2000. Interaction and functional cooperation of NF-κB with Smads. Transcriptional regulation of the junB promoter. J. Biol. Chem. 275:28937-46
119. Luo K. 2004. Ski and SnoN: negative regulators of TGF-β signaling. Curr. Opin. Genet. Dev. 14:65-70
120. Luo K, Stroschein SL, Wang W, Chen D, Martens E, et al. 1999. The Ski oncoprotein interacts with the Smad proteins to repress TGFβ signaling. Genes Dev. 13:2196-206
121. Macias-Silva M, Hoodless PA, Tang SJ, Buchwald M, Wrana JL. 1998. Specific activation of Smad1 signaling pathways by the BMP7 type I receptor, ALK2. J. Biol. Chem. 273:25628-36
122. Marty T, Muller B, Basler K, Affolter M. 2000. Schnurri mediates Dpp-dependent repression of brinker transcription. Nat. Cell Biol. 2:745-49
123. Massagué J. 2003. Integration of Smad and MAPK pathways: a link and a linker revisited. Genes Dev. 17:2993-97
124. Matsuda T, Yamamoto T, Muraguchi A, Saatcioglu F. 2001. Cross-talk between transforming growth factor-β and estrogen receptor signaling through Smad3 .J. Biol. Chem. 276:42908-14
125. Matsuura I, Denissova NG, Wang G, He D, Long J, et al. 2004. Cyclin-dependent kinases regulate the antiproliferative function of Smads. Nature 430:226-31
126. Miura S, Takeshita T, Asao H, Kimura Y, Murata K, et al. 2000. Hgs (Hrs), a FYVE domain protein, is involved in Smad signaling through cooperation with SARA. Mol. Cell Biol. 20:9346-55
127. Miyazono K. 2000. Positive and negative regulation of TGF-β signaling. J. Cell Sci. 113:1101-9
128. Mochizuki T, Miyazaki H, Hara T, Furuya T, Imamura T, et al. 2004. Roles for the MH2 domain of Smad7 in the specific inhibition of transforming growth factor-β superfamily signaling. J Biol. Chem. 279:31568-74
129. Murakami G, Watabe T, Takaoka K, Miyazono K, Imamura T. 2003. Cooperative inhibition of bone morphogenetic protein signaling by Smurf1 and inhibitory Smads. Mol. Biol. Cell 14:2809-17
130. Nakao A, Afrakhte M, Morén A, Nakayama T, Christian J, et al. 1997. Identification of Smad7, a TGFβ-inducible antagonist of TGF-β signalling. Nature 389:631-35
131. Nishita M, Hashimoto MK, Ogata S, Laurent MN, Ueno N, et al. 2000. Interaction between Wnt and TGF-β signalling pathways during formation of Spemann's organizer. Nature 403:781-85
132. Nishitoh H, Ichijo H, Kimura M, Matsumoto T, Makashima F, et al. 1996. Identification of type I and type II receptors for Growth/Differentiation Factor-5. J. Biol. Chem. 271:21345-52
133. Panopoulou E, Gillooly DJ, Wrana JL, Zerial M, Stenmark H, et al. 2002. Early endosomal regulation of Smad-dependent signaling in endothelial cells. J Biol. Chem. 277:18046-52
134. Pardali E, Xie XQ, Tsapogas P, Itoh S, Arvanitidis K, et al. 2000. Smad and AML proteins synergistically confer transforming growth factor β1 responsiveness to human germ-line IgA genes. J. Biol. Chem. 275:3552-60
135. Waf1/Cip1 regulation by transforming growth factor-β. J. Biol. Chem. 275:29244-56
136. Pendaries V, Verrecchia F, Michel S, Mauviel A. 2003. Retinoic acid receptors interfere with the TGF-β/Smad signaling pathway in a ligand-specific manner. Oncogene 22:8212-20
137. Pera EM, Ikeda A, Eivers E, De Robertis EM. 2003. Integration of IGF, FGF, and anti-BMP signals via Smad1 phosphorylation in neural induction. Genes Dev. 17:3023-28
138. Postigo AA. 2003. Opposing functions of ZEB proteins in the regulation of the TGFβ/BMP signaling pathway. EMBO J. 22:2443-52
139. Postigo AA, Depp JL, Taylor JJ, Kroll KL. 2003. Regulation of Smad signaling through a differential recruitment of coactivators and corepressors by ZEB proteins. EMBO J. 22:2453-62
140. Pulaski L, Landstrom M, Heldin CH, Souchelnytskyi S. 2001. Phosphorylation of Smad7 at Ser-249 does not interfere with its inhibitory role in transforming growth factor-β-dependent signaling but affects Smad7-dependent transcriptional activation. J. Biol. Chem. 276:14344-49
141. Qin BY, Chacko BM, Lam SS, de Caestecker MP, Correia JJ, et al. 2001. Structural basis of Smad1 activation by receptor kinase phosphorylation. Mol. Cell 8:1303-12
142. Qin BY, Lam SS, Correia JJ, Lin K. 2002. Smad3 allostery links TGF-β receptor kinase activation to transcriptional control. Genes Dev. 16:1950-63
143. Qin BY, Liu C, Lam SS, Srinath H, Delston R, et al. 2003. Crystal structure of IRF-3 reveals mechanism of autoinhibition and virus-induced phosphoactivation. Nat. Struct. Biol. 10:913-21
144. Qing J, Liu C, Choy L, Wu RY, Pagano JS, et al. 2004. Transforming growth factor β/Smad3 signaling regulates IRF-7 function and transcriptional activation of the β interferon promoter. Mol. Cell Biol. 24:1411-25
145. Qing J, Zhang Y, Derynck R. 2000. Structural and functional characterization of the TGF-β-induced Smad3/c-Jun transcriptional cooperativity. J. Biol. Chem. 275:38802-12
146. Qiu P, Feng X-H, Li L. 2003. Interaction of Smad3 and SRF-associated complex mediates TGF-β1 signals to regulate SM22 transcription during myofibroblast differentiation. J. Mol. Cell. Cardial. 35:1407-20
147. Randall RA, Germain S, Inman GJ, Bates PA, Hill CS. 2002. Different Smad2 partners bind a common hydrophobic pocket in Smad2 via a denned proline-rich motif. EMBO J. 21:145-56
148. Randall RA, Howell M, Page CS, Daly A, Bates PA, et al. 2004. Recognition of phosphorylated-Smad2-containing complexes by a novel Smad interaction motif. Mol. Cell Biol. 24:1106-21
149. Remy I, Montmarquette A, Michnick SW. 2004. PKB/Akt modulates TGF-β signalling through a direct interaction with Smad3. Nat. Cell Biol. 6:358-65
150. Saha D, Datta PK, Beauchamp RD. 2001. Oncogenic ras represses transforming growth factor-β/Smad signaling by degrading tumor suppressor Smad4. J. Biol. Chem. 276:29531-37
151. Samad T, Rebbapragada A, Bell E, Zhang Y, Sidis Y, et al. 2005. DRAGON: a bone morphogenetic protein co-receptor. J. Biol. Chem. 280:14122-29
152. Sanchez-Elsner T, Botella LM, Velasco B, Corbi A, Attisano L, Bernabeu C. 2001. Synergistic cooperation between hypoxia and transforming growth factor-β pathways on human vascular endothelial growth factor gene expression. J. Biol. Chem. 276:38527-35
153. Sano Y, Harada J, Tashiro S, Gotoh-Mandeville R, Maekawa T, et al. 1999. ATF-2 is a common nuclear target of Smad and TAK1 pathways in transforming growth factor-β signaling. J. Biol. Chem. 274:8949-57
154. Sebald W, Mueller TD. 2003. The interaction of BMP-7 and ActRII implicates a new mode of receptor assembly. Trends Biochem. Sci. 28:518-21
155. Seoane J, Le HV, Massagué J. 2002. Myc suppression of the p21(Cip1) Cdk inhibitor influences the outcome of the p53 response to DNA damage. Nature 419:729-34
156. Seoane J, Le HV, Shen L, Anderson SA, Massagué J. 2004. Integration of Smad and fork-head pathways in the control of neuroepithelial and glioblastoma cell proliferation. Cell 117:211-23
157. INK4b. Nat. Cell Biol. 3:400-8
158. Shi X, Yang X, Chen D, Chang Z, Cao X. 1999. Smad1 interacts with homeobox DNA-binding proteins in bone morphogenetic protein signaling. J. Biol. Chem. 274:13711-17
159. Shi Y, Hata A, Lo RS, Massagué J, Pavletich N. 1997. A structural basis for mutational inactivation of the tumour suppressor Smad4. Nature 388:87-93
160. Shi Y, Massagué J. 2003. Mechanisms of TGF-β signaling from cell membrane to the nucleus, Cell 113:685-700
161. Shi Y, Wang Y-F, Jayaraman L, Yang H, Massagué J, et al. 1998. Crystal structure of a Smad MH1 domain bound to DNA: insights on DNA binding in TGF-β signaling. Cell 94:585-94
162. Shimizu K, Bourillot PY, Nielsen SJ, Zorn AM, Gurdon JB. 2001. Swift is a novel BRCT domain coactivator of Smad2 in transforming growth factor β signaling. Mol. Cell Biol. 21:3901-12
163. Shioda T, Lechleider RJ, Dunwoodie SL, Li H, Yahata T, et al. 1998. Transcriptional activating activity of Smad4: roles of SMAD hetero- oligomerization and enhancement by an associating transactivator. Proc. Natl. Acad. Sci. USA 95:9785-90
164. Sirotkin HI, Gates MA, Kelly PD, Schier AF, Talbot WS. 2000. Fast1 is required for the development of dorsal axial structures in zebrafish. Curr: Biol. 10:1051-54
165. Song CZ, Tian X, Gelehrter TD. 1999. Glucocorticoid receptor inhibits transforming growth factor-β signaling by directly targeting the transcriptional activation function of Smad3. Proc. Natl. Acad. Sci. USA 96:11776-81
166. Souchelnytskyi S, Nakayama T, Nakao A, Morén A, Heldin CH, et al. 1998. Physical and functional interaction of murine and Xenopus Smad7 with bone morphogenetic protein receptors and transforming growth factor-β receptors. J. Biol. Chem. 273:25364-70
167. Sun Y, Liu X, Ng-Eaton E, Lodish HF, Weinberg RA. 1999. SnoN and Ski protooncoproteins are rapidly degraded in response to transforming growth factor β signaling. Proc. Natl. Acad. Sci. USA 96:12442-47
168. Suzuki C, Murakami G, Fukuchi M, Shimanuki T, Shikauchi Y, et al. 2002. Smurf1 regulates the inhibitory activity of Smad7 by targeting Smad7 to the plasma membrane. J. Biol. Chem. 277:39919-25
169. Takebayashi-Suzuki K, Funami J, Tokumori D, Saito A, Watabe T, et al. 2003. Interplay between the tumor suppressor p53 and TGF β signaling shapes embryonic body axes in Xenopus. Development 130:3929-39
170. Topper J, Cai J, Qiu Y, Anderson K, Xu Y-Y, et al. 1997. Vascular MADs: two novel MAD-related genes selectively inducible by flow in human vascular endothelium. Proc. Natl. Acad. Sci. USA 94:9314-19
171. Tsukazaki T, Chiang TA, Davison AF, Attisano L, Wrana JL. 1998. SARA, a FYVE domain protein that recruits Smad2 to the TGFβ receptor. Cell 95:779-91
172. Tzachanis D, Freeman GJ, Hirano N, van Puijenbroek AA, Delfs MW, et al. 2001. Tob is a negative regulator of activation that is expressed in anergic and quiescent T cells. Nat. Immunol. 2:1174-82
173. Ulloa L, Doody J, Massagué J. 1999. Inhibition of transforming growth factor-β/SMAD signalling by the interferon-γ/STAT pathway. Nature 397:710-13
174. Verschueren K, Remade JE, Collart C, Kraft H, Baker BS, et al. 1999. SIP1, a novel Zinc finger/homeodomain represser, interacts with Smad proteins and binds to 5′-CACCT sequences in candidate target genes. J. Biol. Chem. 274:20489-98
175. von Both I, Silvestri C, Erdemir T, Lickert H, Walls JR, et al. 2004. Foxh1 is essential for development of the anterior heart field. Dev. Cell 7:331-45
176. Waddell DS, Liberati NT, Guo X, Frederick JP, Wang XF. 2004. Casein kinase Iε plays a functional role in the transforming growth factor-β signaling pathway. J. Biol. Chem. 279:29236-46
177. Wang G, Long J, Matsuura I, He D, Liu F. 2005. The Smad3 linker region contains a transcriptional activation domain. Biochem. J. 386:29-34
178. Wang W, Mariani FV, Harland RM, Luo K. 2000. Ski represses bone morphogenic protein signaling in Xenopus and mammalian cells. Proc. Natl. Acad. Sci. USA 97:14394-99
179. Warner DR, Roberts EA, Greene RM, Pisano MM. 2003. Identification of novel Smad binding proteins. Biochem. Biophys. Res. Commun. 312:1185-90
180. Wilkinson DS, Ogden SK, Stratton SA, Piechan JL, Nguyen TT, et al. 2005. A direct intersection between p53 and transforming growth factor β pathways targets chromatin modification and transcription repression of the α-fetoprotein gene. Mol. Cell Biol. 25:1200-12
181. Wotton D, Massagué J. 2001. Smad transcriptional corepressors in TGF β family signaling. Curr. Top. Microbiol. Immunol. 254:145-64
182. Wu G, Chen YG, Ozdamar B, Gyuricza CA, Chong PA, et al. 2000. Structural basis of Smad2 recognition by the Smad anchor for receptor activation. Science 287:92-97
183. Wu JW, Fairman R, Penry J, Shi Y. 2001. Formation of a stable heterodimer between Smad2 and Smad4. J. Biol. Chem. 276:20688-94
184. Wu JW, Hu M, Chai J, Seoane J, Huse M, et al. 2001. Crystal structure of a phosphorylated Smad2. Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGF-β signaling. Mol. Cell 8:1277-89
185. Wu JW, Krawitz AR, Chai J, Li W, Zhang F, et al. 2002. Structural mechanism of Smad4 recognition by the nuclear oncoprotein Ski: insights on Ski-mediated repression of TGF-β signaling. Cell 111:357-67
186. Wu L, Wu Y, Gathings B, Wan M, Li X, et al. 2003. Smad4 as a transcription corepressor for estrogen receptor a. J. Biol. Chem. 278:15192-200
187. Yagi K, Furuhashi M, Aoki H, Goto D, Kuwano H, et al. 2002. c-myc is a downstream target of the Smad pathway. J. Biol. Chem. 277:854-61
188. Yagi K, Goto D, Hamamoto T, Takenoshita S, Kato M, et al. 1999. Alternatively spliced variant of Smad2 lacking exon 3. Comparison with wild-type Smad2 and Smad3. J. Biol. Chem. 274:703-9
189. Yakymovych I, ten Dijke P, Heldin CH, Souchelnytskyi S. 2001. Regulation of Smad signaling by protein kinase C. FASEB J. 15:553-55
190. Yamakawa N, Tsuchida K, Sugino H. 2002. The rasGAP-binding protein, Dok-1, mediates activin signaling via serine/threonine kinase receptors. EMBO J. 21:1684-94
191. Yamamoto M, Meno C, Sakai Y, Shiratori H, Mochida K, et al. 2001. The transcription factor FoxH1 (FAST) mediates Nodal signaling during anterior-posterior patterning and node formation in the mouse. Genes Dev. 15:1242-56
192. Yamamoto T, Saatcioglu F, Matsuda T. 2002. Cross-talk between bone morphogenic proteins and estrogen receptor signaling. Endocrinology 143:2635-42
193. Yanagisawa J, Yanagi Y, Masuhiro Y, Suzawa M, Watanabe M, et al. 1999. Convergence of transforming growth factor-β and vitamin D signaling pathways on SMAD transcriptional coactivators. Science 283:1317-21
194. Yeo C, Whitman M. 2001. Nodal signals to Smads through Cripto-dependent and Cripto-independent mechanisms. Mol. Cell 7:949-57
195. Yoshida Y, Tanaka S, Umemori H, Minowa O, Usui M, et al. 2000. Negative regulation of BMP/Smad signaling by Tob in osteoblasts. Cell 103:1085-97
196. Yoshida Y, von Bubnoff A, Ikematsu N, Blitz IL, Tsuzuku JK, et al. 2003. Tob proteins enhance inhibitory Smad-receptor interactions to repress BMP signaling. Mech. Dev. 120:629-37
197. Zauberman A, Lapter S, Zipori D. 2001. Smad proteins suppress CCAAT/enhancer-binding protein (C/EBP) β- and STAT3-mediated transcriptional activation of the haptoglobin promoter. J. Biol. Chem. 276:24719-25
198. Zavadil J, Cermak L, Soto-Nieves N, Böttinger EP. 2004. Integration of TGF-β/Smad and Jagged1/Notch signalling in epithelial-to-mesenchymal transition. EMEO J. 23:1155-65
199. Zawel L, Dai JL, Buckhaults P, Zhou S, Kinzler KW, et al. 1998. Human Smad3 and Smad4 are sequence-specific transcription activators. Mol. Cell. 1:611-17
200. Zhang Y, Derynck R. 2000. Transcriptional regulation of the transforming growth factor-β-inducible mouse germ line Iga constant region gene by functional cooperation of Smad, CREB, and AML family members. J. Biol. Chem. 275:16979-85
201. Zhang Y, Feng X-H, Derynck R. 1998. Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-β-induced transcription. Nature 394:909-13
202. Zhang YW, Yasui N, Ito K, Huang G, Fujii M, et al. 2000. A RUNX2/PEBP2αA/CBFA1 mutation displaying impaired transactivation and Smad interaction in cleidocranial dysplasia. Proc. Natl. Acad. Sci. USA 97:10549-54
203. Zhou S, Zawel L, Lengauer C, Kinzler KW, Vogelstein B. 1998. Characterization of human FAST-1, a TGF β and activin signal transducer. Mol. Cell 2:121-17