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Science 286 (5440): 771-774

Copyright © 1999 by the American Association for the Advancement of Science

Negative Feedback Regulation of TGF-beta Signaling by the SnoN Oncoprotein

Shannon L. Stroschein, 12 Wei Wang, 1 Sharleen Zhou, 2 Qiang Zhou, 2 Kunxin Luo 12*

Smad proteins mediate transforming growth factor-beta (TGF-beta ) signaling to regulate cell growth and differentiation. The SnoN oncoprotein was found to interact with Smad2 and Smad4 and to repress their abilities to activate transcription through recruitment of the transcriptional corepressor N-CoR. Immediately after TGF-beta stimulation, SnoN is rapidly degraded by the nuclear accumulation of Smad3, allowing the activation of TGF-beta target genes. By 2 hours, TGF-beta induces a marked increase in SnoN expression, resulting in termination of Smad-mediated transactivation. Thus, SnoN maintains the repressed state of TGF-beta -responsive genes in the absence of ligand and participates in negative feedback regulation of TGF-beta signaling.

1 Life Sciences Division, Lawrence Berkeley National Laboratory, and
2 Department of Molecular and Cell Biology, University of California, Berkeley, 229 Stanley Hall, Mail Code 3206, Berkeley, CA 94720, USA.
*   To whom correspondence should be addressed. E-mail: k_luo{at}ux5.lbl.gov

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   Abstract »    Full Text »    PDF »
Proteasomal Degradation of Smad1 Induced by Bone Morphogenetic Proteins.
C. Gruendler, Y. Lin, J. Farley, and T. Wang (2001)
J. Biol. Chem. 276, 46533-46543
   Abstract »    Full Text »    PDF »
TGF-beta inhibits muscle differentiation through functional repression of myogenic transcription factors by Smad3.
D. Liu, B. L. Black, and R. Derynck (2001)
Genes & Dev. 15, 2950-2966
   Abstract »    Full Text »    PDF »
Cross-talk between Transforming Growth Factor-beta and Estrogen Receptor Signaling through Smad3.
T. Matsuda, T. Yamamoto, A. Muraguchi, and F. Saatcioglu (2001)
J. Biol. Chem. 276, 42908-42914
   Abstract »    Full Text »    PDF »
Smad3 recruits the anaphase-promoting complex for ubiquitination and degradation of SnoN.
S. L. Stroschein, S. Bonni, J. L. Wrana, and K. Luo (2001)
Genes & Dev. 15, 2822-2836
   Abstract »    Full Text »    PDF »
Synergistic Cooperation between Hypoxia and Transforming Growth Factor-beta Pathways on Human Vascular Endothelial Growth Factor Gene Expression.
T. Sanchez-Elsner, L. M. Botella, B. Velasco, A. Corbi, L. Attisano, and C. Bernabeu (2001)
J. Biol. Chem. 276, 38527-38535
   Abstract »    Full Text »    PDF »
The Smad Transcriptional Corepressor TGIF Recruits mSin3.
D. Wotton, P. S. Knoepfler, C. D. Laherty, R. N. Eisenman, and J. Massague (2001)
Cell Growth Differ. 12, 457-463
   Abstract »    Full Text »    PDF »
Regulation of myostatin activity and muscle growth.
S.-J. Lee and A. C. McPherron (2001)
PNAS 98, 9306-9311
   Abstract »    Full Text »    PDF »
Gremlin negatively modulates BMP-4 induction of embryonic mouse lung branching morphogenesis.
W. Shi, J. Zhao, K. D. Anderson, and D. Warburton (2001)
Am J Physiol Lung Cell Mol Physiol 280, L1030-L1039
   Abstract »    Full Text »    PDF »
Ligand-dependent Degradation of Smad3 by a Ubiquitin Ligase Complex of ROC1 and Associated Proteins.
M. Fukuchi, T. Imamura, T. Chiba, T. Ebisawa, M. Kawabata, K. Tanaka, and K. Miyazono (2001)
Mol. Biol. Cell 12, 1431-1443
   Abstract »    Full Text »
The corepressor CtBP interacts with Evi-1 to repress transforming growth factor {beta} signaling.
K. Izutsu, M. Kurokawa, Y. Imai, K. Maki, K. Mitani, and H. Hirai (2001)
Blood 97, 2815-2822
   Abstract »    Full Text »    PDF »
Human T-cell leukemia virus type I oncoprotein Tax represses Smad-dependent transforming growth factor {beta} signaling through interaction with CREB-binding protein/p300.
N. Mori, M. Morishita, T. Tsukazaki, C.-Z. Giam, A. Kumatori, Y. Tanaka, and N. Yamamoto (2001)
Blood 97, 2137-2144
   Abstract »    Full Text »    PDF »
Inactivation of menin, a Smad3-interacting protein, blocks transforming growth factor type {beta} signaling.
H. Kaji, L. Canaff, J.-J. Lebrun, D. Goltzman, and G. N. Hendy (2001)
PNAS 98, 3837-3842
   Abstract »    Full Text »    PDF »
SMAD3 Represses Androgen Receptor-mediated Transcription.
S. A. Hayes, M. Zarnegar, M. Sharma, F. Yang, D. M. Peehl, P. t. Dijke, and Z. Sun (2001)
Cancer Res. 61, 2112-2118
   Abstract »    Full Text »
Caveolin-1 Regulates Transforming Growth Factor (TGF)-beta /SMAD Signaling through an Interaction with the TGF-beta Type I Receptor.
B. Razani, X. L. Zhang, M. Bitzer, G. von Gersdorff, E. P. Bottinger, and M. P. Lisanti (2001)
J. Biol. Chem. 276, 6727-6738
   Abstract »    Full Text »    PDF »

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