Smads as transcriptional co-modulators

Current Opinion in Cell Biology

Volumn 12, Issue 2, 2000, Pages 235-243

  Attisano, Liliana ^a   Wrana, Jeffrey L ^b  

^a UNIVERSITY OF TORONTO   (Canada)

^b MOUNT SINAI HOSPITAL   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVIN; DNA; DNA BINDING PROTEIN; RECEPTOR; SMAD PROTEIN; TRANSCRIPTION FACTOR; TRANSFORMING GROWTH FACTOR BETA;

PRIORITY JOURNAL; PROTEIN DNA BINDING; PROTEIN PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION; TRANSCRIPTION REGULATION;

EID: 0034104591     PISSN: 09550674     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0955-0674(99)00081-2     Document Type: Review

References (63)

1. Heldin C-H., Miyazono K., ten Dijke P. TGF-β signalling from cell membrane to nucleus through SMAD proteins. Nature. 390:1997;465-471.
2. Massagué J. TGF-β Signal Transduction. Annu Rev Biochem. 67:1998;753-791.
3. Attisano L., Wrana J.L. Mads and Smads in TGFβ signalling. Curr Opin Cell Biol. 10:1998;188-194.
4. Derynck R., Zhang Y., Feng X-H. Smads: transcriptional activators of TGF-β responses. Cell. 95:1998;737-740.
5. Christian J.L., Nakayama T. Can't get no SMADisfaction: Smad proteins as positive and negative regulators of TGF-β family signals. BioEssays. 21:1999;382-390.
6. Ulloa L., Doody J., Massagué J. Inhibition of transforming growth factor-β/SMAD signalling by the interferon-ν/STAT pathway. Nature. 397:1999;710-713.
7. Itoh S., Landstrom M., Hermansson A., Itoh F., Heldin C-H., Heldin N-E., ten Dijke P. Transforming growth factor β1 induces nuclear export of inhibitory Smad7. J Biol Chem. 273:1998;29195-29201.
8. Zhu H.J., Iaria J., Sizeland A.M. Smad7 differentially regulates transforming growth factorβ-mediatedsignaling pathways. J Biol Chem. 274:1999;32258-32264.
9. Lo R.S., Chen Y-G., Shi Y., Pavletich N.P., Massagué J. The L3 loop: a structural motif determining specific interactions between SMAD proteins and TGF-β receptors. EMBO J. 17:1998;996-1005.
10. Tsukazaki T., Chiang T.A., Davison A.F., Attisano L., Wrana J.L. SARA, a FYVE domain protein that recruits Smad2 to the TGF-β receptor. Cell. 95:1998;779-791. The first step in the initiation of the intracellular signalling cascade is the association of a R-Smad with the receptor complex. In this paper, SARA (for Smad anchor for receptor activation) was identified and was shown to be important for this process. In addition to Smad and receptor-interacting domains, SARA contains a FYVE domain, which in other proteins has been shown anchor proteins to membranes. These findings demonstrate that SARA can recruit Smad to membranes and regions of the cell where the activating receptor kinase is localized.
11. Lagna G., Hata A., Hemmati-Brivanlou A., Massagué J. Partnership between DPC4 and SMAD proteins in TGF-β signalling pathways. Nature. 383:1996;832-836.
12. Liu F., Hata A., Baker J., Doody J., Cárcamo J., Harland R., Massagué J. A human Mad protein acting as a BMP-regulated transcriptional activator. Nature. 381:1996;620-623.
13. Baker J.C., Harland R. A novel mesoderm inducer, Madr2, functions in the activin signal transduction pathway. Genes Dev. 10:1996;1880-1889.
14. Hata A., Lo R.S., Wotton D., Lagna G., Massagué J. Mutations increasing autoinhibition inactivate tumour suppressors Smad2 and Smad4. Nature. 388:1997;82-87.
15. Shi Y., Hata A., Lo R.S., Massagué J., Pavletich N.P. A structural basis for mutational inactivation of the tumour suppressor Smad4. Nature. 388:1997;87-93.
16. Kawabata M., Inoue H., Hanyu A., Imamura T., Miyazono K. Smad proteins exist as monomers in vivo and undergo homo- and hetero-oligomerization upon activation by serine/threonine kinase receptors. EMBO J. 17:1998;4056-4065. Using a combination of biochemical approaches, this paper investigates the stoichiometry of the Smad complex. They show that in mammalian cells, Smads exist as monomers and assemble into trimeric complexes upon activation of the pathway.
17. Wu G., Chen Y-G., Ozdamar B., Gyuricza C., Chong P.A., Wrana J.L., Massagué J., Shi Y. Structural basis of Smad2 recognition by the Smad anchor for receptor activation. Science. 287:2000;92-97. This paper reports the structure of the Smad2 MH2 domain bound to a peptide derived from SARA. This is the first report of on the structural basis for specificity in protein-protein interactions in the Smad pathway and provides some insights into how R-Smad substrates might be recognized by activated type I receptors.
18. Chen Y-G., Massagué J. Smad1 recognition and activation by the ALK1 group of transforming growth factor-β family receptors. J Biol Chem. 274:1999;3672-3677.
19. Chen Y-G., Hata A., Lo R.S., Wotton D., Shi Y., Pavletich N., Massagué J. Determinants of specificity in TGF-β signal transduction. Genes Dev. 12:1998;2144-2152.
20. Feng X-H., Derynck R. A kinase subdomain of transforming growth factor-β (TGF-β) type 1 receptor determines the TGF-β intracellular signaling specificity. EMBO J. 16:1997;3912-3923.
21. Shi Y., Wang Y-F., Jayaraman L., Yang H., Massagué J., 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.
22. Kretzschmar M., Doody J., Massagué J. Opposing BMP and EGF signalling pathways converge on the TGF-β family mediator Smad1. Nature. 389:1997;618-622.
23. Kretzschmar M., Doody J., Timokhina I., Massagué J. A mechanism of repression of TGFβ TGFβ/Smad signalling by oncogenic Ras. Genes Dev. 13:1999;804-816.
24. Zhu H., Kavsak P., Abdollah S., Wrana J.L., Thomsen G.H. A SMAD ubiquitin ligase targets the BMP pathway and affects embryonic pattern formation. Nature. 400:1999;687-693. This paper identifies a Smad1 partner that functions to target the Smad for degradation by the ubiquitin-proteasome system. This reveals a function for ubiquitination in regulating the activity of the Smad pathway.
25. Brummel T., Abdollah S., Haerry T.E., Shimell M.H., Merriam J., Raftery L., Wrana J.L., O'Connor M.B. The Drosophila activin receptor Baboon signals through DSmad2 and controls cell proliferation but not patterning during larval development. Genes Dev. 13:1999;98-111. Previously no TGFβ/activin-like pathway was known in Drosophila. In this paper a TGFβ/activin-like pathway is identified that involves the receptor Babo and a Drosophila homologue of Smad2 and Smad3. Interestingly, this pathway controls growth during fly development but does not regulate patterning.
26. Hershko A., Ciechanover A. The ubiquitin system. Annu Rev Biochem. 67:1998;425-479.
27. Lo R.S., Massagué J. Ubiquitin-dependent degradation of TGF-activated Smad2. Nat Cell Biol. 1:1999;472-478. This paper describes a nuclear mechanism to turn off Smad signalling. Smads that enter the nucleus are shown to be degraded via the ubiquitin-proteasome system, thereby leading to reductions in the levels of activated Smads.
28. •].
29. •].
30. •].
31. •].
32. •] demonstrate that Ski and SnoN are rapidly degraded in response to TGFβ. Thus, ubiquitin-mediated proteolysis of these Smad corepressors may play an important role in TGFβ signalling.
33. Kim J., Johnson K., Chen H.J., Carroll S., Laughon A. Drosophila Mad binds to DNA and directly mediates activation of vestigial by decapentaplegic. Nature. 388:1997;304-308.
34. 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;611-617.
35. Johnson K., Kirkpatrick H., Comer A., Hoffmann F.M., Laughon A. Interaction of Smad complexes with tripartite DNA-binding sites. J Biol Chem. 274:1999;20709-20716.
36. Yagi K., Goto D., Hamamoto T., Takenoshita S., Kato M., Miyazono K. Alternatively Spliced Variant of Smad2 lacking exon3. J Biol Chem. 274:1999;703-709.
37. Chen X., Rubock M.J., Whitman M. A transcriptional partner for MAD proteins in TGF-β signalling. Nature. 383:1996;691-696.
38. 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.
39. Labbé E., Silvestri C., Hoodless P.A., Wrana J.L., Attisano L. Smad2 and Smad3 positively and negatively regulate TGFβ-dependent transcription through the forkhead DNA binding protein, FAST2. Mol Cell. 2:1998;109-120.
40. Weisberg E., Winnier G.E., Chen X., Farnsworth C.L., Hogan B.L.H., Whitman M. A mouse homologue of FAST-1 transduces TGFβ superfamily signals and is expressed during early embryogenesis. Mech Dev. 79:1998;17-27.
41. Zhou S., Zawel L., Lengauer C., Kinzler K.W., Vogelstein B. Characterization of human FAST-1, a TGFβ and activin signal transducer. Mol Cell. 2:1998;121-127.
42. 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.
43. Liu F., Pouponnot C., Massagué J. Dual role of the Smad4/DPC4 tumor suppressor in TGFβ-inducible transcriptional complexes. Genes Dev. 11:1997;3157-3167.
44. Yeo C-Y., Chen X., Whitman M. The role of FAST-1 and Smads in transcriptional regulation by activin during early Xenopus embryogenesis. J Biol Chem. 274:1999;26584-26590.
45. Zhang Y., Feng X-H., Derynck R. Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGFβ-induced transcription. Nature. 394:1998;909-913. The authors describe the interaction of Smads with Jun and Fos and shows how promoters containing AP1 elements can respond to TGFβ signalling through cooperation with the Smad signalling pathway. This is the first report to suggest that Smads may crosstalk with other signalling pathways in the nucleus.
46. 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.
47. Hocevar B.A., Brown T.L., Howe P.H. TGF-β induces fibronectin synthesis through a c-Jun N-terminal kinase-dependent, Smad4-independent pathway. EMBO J. 18:1999;1345-1356.
48. Hanafusa H., Ninomiya-Tsuji J., Masuyama N., Nishita M., Fujisawa J., Shibuya H., Matsumoto K., Nishida E. Involvement of the p38 mitogen-activated protein kinase pathway in transforming growth factor-β-induced gene expression. J Biol Chem. 274:1999;27161-27167.
49. 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.
50. Eresh S., Riese J., Jackson D.B., Bohmann D., Bienz M. A CREB-binding site as a target for decapentaplegic signalling during Drosophila endoderm induction. EMBO J. 16:1997;2014-2022.
51. Hua X., Miller Z.A., Wu G., Shi Y., Lodish H.F. 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. 96:1999;13130-13135.
52. Hanai J-I., Chen L.F., Kanno T., Ohtani-Fujita N., Kim W.Y., Guo W-H., Imamura T., Ishidou Y., Fukuchi M., Shi M-J.et al. Interaction and functional cooperation of PEBP2/CBF with Smads. J Biol Chem. 274:1999;31577-31582.
53. Liu F., Massagué J., Altaba A.R.I. Carboxy-terminally truncated Gli3 proteins associate with Smads. Nat Genet. 20:1999;325-326.
54. 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 signalling pathways on SMAD transcriptional coactivators. Science. 283:1999;1317-1321. This paper shows that Smads can target the vitamin D receptor and potentiate vitamin-D-dependent transcription. Interaction of Smads with the hormone receptor is shown to be dependent on vitamin D and the binding of the SRC-1 co-activators. Thus, TGFβ signalling can crosstalk with the vitamin D pathway.
55. Shi X., Yang X., Chen D., Chang Z., Cao X. Smad1 interacts with homeobox DNA-binding proteins in bone morphogenetic protein signalling. J Biol Chem. 274:1999;13711-13717. This paper shows that Smads can interact with homeobox-binding proteins and prevent their interaction with target elements. The authors propose that by preventing Hox8c from repressing the osteopontin promoter, Smad1 can activate this gene in response to BMP signalling.
56. Verschueren K., Remacle J.E., Collart C., Kraft H., Baker B.S., Tylzanowski P., Nelles L., Wuytens G., Su M-T., Bodmer R.et al. 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.
57. Shioda T., Lechleider R.J., Dunwoodie S.L., Li H., Yahata T., de Caestecker M.P., Fenner M.H., Roberts A.B., 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.
58. Nakashima K., Yanagisawa M., Arakawa H., Kimura N., Hisatsune T., Kawabata M., Miyazono K., Taga T. Synergistic signalling in fetal brain by STAT3-Smad1 complex bridged by p300. Science. 284:1999;479-482.
59. Wotton D., Lo R.S., Lee S., Massagué J. A Smad transcriptional corepressor. Cell. 97:1999;29-39. This paper is the first to show that Smads can recruit co-repressors to target elements and via these interactions repress activation of target genes.
60. Kurokawa M., Mitani K., Irie K., Matsuyama T., Takahashi T., Chiba S., Yazaki Y., Matsumoto K., Hirai H. The oncoprotein Evi-1 represses TGF-β signalling by inhibiting Smad3. Nature. 394:1998;92-96.
61. Hata A., Seoane J., Lagna G., Montalvo E., Hemmati-Brivanlou A., Massagué J. OAZ uses distinct DNA- and protein-binding zinc fingers in separate BMP-Smad and Olf signaling pathways. Cell. 100:2000;229-240. In this paper a 30-zinc finger protein, OAZ, is identified as a DNA-binding partner for Smads in the BMP signaling pathway that functions to activate transcription of Xvent2. One cluster of zinc fingers was shown to mediate Smad binding whereas a second set is required for fulfilling its function as a transcriptional partner for Olf-1/EBF in olfactory epithelium. Thus, this paper describes a dual role for multi-zinc finger proteins in signal transduction.
62. Xu J., Attisano L. Mutations in the tumour suppressors Smad2 and Smad4 inactivate TGFβ signalling by targeting Smads to the ubiquitin-proteasome pathway. Proc Natl Acad Sci USA. 2000;. in press. In this manuscript, mutations in a conserved arginine residue in the MH1 domain of Smads are shown to target Smads for ubiquitination and degradation. As these mutations were originally identified in human colorectal and pancreatic cancers the results reveal a mechanism for tumorigenesis whereby genetic defects in the tumor-suppressor Smad proteins induce loss of function through protein degradation via the ubiquitin-proteasome pathway.
63. Dong C., Li Z., Goldschmidt-Clermont P.J. Microtubule binding to Smads may regulate TGFβ activity. Mol Cell. 5:2000;27-34. In this paper, endogenous Smads are shown to bind to microtubules (MTs) in a ligand-independent manner. Destabilization of the MT network increases TGFβ-induced transcription and suggests a novel function for the MT network in negatively regulating Smad activity.