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J Biol Chem, Vol. 274, Issue 47, 33412-33418, November 19, 1999
From the Department of Medical and Molecular Genetics and the
Walther Oncology Center, Indiana University School of Medicine,
Indianapolis, Indiana 46202
Smad7 is a regulatory Smad protein that is able
to antagonize signal transduction by transforming growth factor-
(TGF-) and activin receptors. To characterize the regulation of
Smad7 at the transcriptional level, we isolated the promoter region of
the mouse Smad7 gene. When the Smad7 promoter luciferase
reporter gene (
408 and +112 bp) was expressed in human hepatoma
(HepG2) cells, its transcriptional activity was increased following
TGF- or activin treatment. In addition, this region of the Smad7
promoter was stimulated by ectopic expression of Smad3 as well as
constitutively active TGF- and activin receptors, indicating that
Smad7 transcription was modulated by the signaling downstream those two
receptors. A gel mobility shift assay indicated that a DNA fragment
spanning 408 to 126 base pairs (bp) was able to directly bind
purified Smad4. Furthermore, a consensus Smad3-Smad4 binding element
(SBE) was discovered in this region of the promoter with a palindromic sequence of GTCTAGAC. A 33-bp Smad7 promoter fragment containing this
SBE was able to bind Smad3 and Smad4. In human embryonic kidney 293 cells, the expression of constitutively active TGF- type I receptor
was able to induce the formation of a Smad3- and Smad4-containing
nuclear protein complex that bound the SBE. In HepG2 cells, TGF-1
treatment could induce the formation of an endogenous SBE-binding
complex. Taken together, these data provided the first evidence that
Smad7 transcription is regulated by TGF- and activin signaling
through direct binding of Smad3 and Smad4 to the Smad7 promoter.
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T. A. Melhuish and D. Wotton The Interaction of the Carboxyl Terminus-binding Protein with the Smad Corepressor TGIF Is Disrupted by a Holoprosencephaly Mutation in TGIF J. Biol. Chem., December 8, 2000; 275(50): 39762 - 39766. [Abstract] [Full Text] [PDF]
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X. Hua, Z. A. Miller, H. Benchabane, J. L. Wrana, and H. F. Lodish Synergism between Transcription Factors TFE3 and Smad3 in Transforming Growth Factor-beta -induced Transcription of the Smad7 Gene J. Biol. Chem., October 20, 2000; 275(43): 33205 - 33208. [Abstract] [Full Text] [PDF]
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K. A. Henningfeld, S. Rastegar, G. Adler, and W. Knochel Smad1 and Smad4 Are Components of the Bone Morphogenetic Protein-4 (BMP-4)-induced Transcription Complex of the Xvent-2B Promoter J. Biol. Chem., July 14, 2000; 275(29): 21827 - 21835. [Abstract] [Full Text] [PDF]
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G. Brodin, A. Ahgren, P. ten Dijke, C.-H. Heldin, and R. Heuchel Efficient TGF-beta Induction of the Smad7 Gene Requires Cooperation between AP-1, Sp1, and Smad Proteins on the Mouse Smad7 Promoter J. Biol. Chem., September 8, 2000; 275(37): 29023 - 29030. [Abstract] [Full Text] [PDF]
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S. Patil, G. M. Wildey, T. L. Brown, L. Choy, R. Derynck, and P. H. Howe Smad7 Is Induced by CD40 and Protects WEHI 231 B-lymphocytes from Transforming Growth Factor-beta -induced Growth Inhibition and Apoptosis J. Biol. Chem., December 1, 2000; 275(49): 38363 - 38370. [Abstract] [Full Text] [PDF]
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A.-C. Poncelet and H. W. Schnaper Sp1 and Smad Proteins Cooperate to Mediate Transforming Growth Factor-beta 1-induced alpha 2(I) Collagen Expression in Human Glomerular Mesangial Cells J. Biol. Chem., March 2, 2001; 276(10): 6983 - 6992. [Abstract] [Full Text] [PDF]
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N. Hill-Kapturczak, L. Truong, V. Thamilselvan, G. A. Visner, H. S. Nick, and A. Agarwal Smad7-dependent Regulation of Heme Oxygenase-1 by Transforming Growth Factor-beta in Human Renal Epithelial Cells J. Biol. Chem., December 22, 2000; 275(52): 40904 - 40909. [Abstract] [Full Text] [PDF]
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Y. Inagaki, T. Nemoto, A. Nakao, P. t. Dijke, K. Kobayashi, K. Takehara, and P. Greenwel Interaction between GC Box Binding Factors and Smad Proteins Modulates Cell Lineage-specific alpha 2(I) Collagen Gene Transcription J. Biol. Chem., May 4, 2001; 276(19): 16573 - 16579. [Abstract] [Full Text] [PDF]
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T. Quan, T. He, J. J. Voorhees, and G. J. Fisher Ultraviolet Irradiation Blocks Cellular Responses to Transforming Growth Factor-beta by Down-regulating Its Type-II Receptor and Inducing Smad7 J. Biol. Chem., July 6, 2001; 276(28): 26349 - 26356. [Abstract] [Full Text] [PDF]
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L. M. Botella, T. Sanchez-Elsner, C. Rius, A. Corbi, and C. Bernabeu Identification of a Critical Sp1 Site within the Endoglin Promoter and Its Involvement in the Transforming Growth Factor-beta Stimulation J. Biol. Chem., September 7, 2001; 276(37): 34486 - 34494. [Abstract] [Full Text] [PDF]
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F. Verrecchia, M.-L. Chu, and A. Mauviel Identification of Novel TGF-beta /Smad Gene Targets in Dermal Fibroblasts using a Combined cDNA Microarray/Promoter Transactivation Approach J. Biol. Chem., May 11, 2001; 276(20): 17058 - 17062. [Abstract] [Full Text] [PDF]
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A. Mazars, F. Lallemand, C. Prunier, J. Marais, N. Ferrand, M. Pessah, G. Cherqui, and A. Atfi Evidence for a Role of the JNK Cascade in Smad7-mediated Apoptosis J. Biol. Chem., September 21, 2001; 276(39): 36797 - 36803. [Abstract] [Full Text] [PDF]
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E. Piek, W. J. Ju, J. Heyer, D. Escalante-Alcalde, C. L. Stewart, M. Weinstein, C. Deng, R. Kucherlapati, E. P. Bottinger, and A. B. Roberts Functional Characterization of Transforming Growth Factor beta Signaling in Smad2- and Smad3-deficient Fibroblasts J. Biol. Chem., June 1, 2001; 276(23): 19945 - 19953. [Abstract] [Full Text] [PDF]
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K. Kusanagi, M. Kawabata, H. K. Mishima, and K. Miyazono alpha -Helix 2 in the Amino-terminal Mad Homology 1 Domain Is Responsible for Specific DNA Binding of Smad3 J. Biol. Chem., July 20, 2001; 276(30): 28155 - 28163. [Abstract] [Full Text] [PDF]
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K. Pardali, A. Kurisaki, A. Moren, P. ten Dijke, D. Kardassis, and A. Moustakas Role of Smad Proteins and Transcription Factor Sp1 in p21Waf1/Cip1 Regulation by Transforming Growth Factor-beta J. Biol. Chem., September 15, 2000; 275(38): 29244 - 29256. [Abstract] [Full Text] [PDF]
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N. G. Denissova, C. Pouponnot, J. Long, D. He, and F. Liu Transforming growth factor beta -inducible independent binding of SMAD to the Smad7 promoter PNAS, June 6, 2000; 97(12): 6397 - 6402. [Abstract] [Full Text] [PDF]
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