NDLI: c-Jun interacts with the corepressor TG-interacting factor (TGIF) to suppress Smad2 transcriptional activity.

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c-Jun interacts with the corepressor TG-interacting factor (TGIF) to suppress Smad2 transcriptional activity.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Ferrand, N. Lallemand, F. Marais, J. Pessah, M. Gauthier, J. M. Prunier, C. Atfi, A. Mazars, A.
Description	Author Affiliation: Pessah M ( Institut National de la Santé et de la Recherche Médicale U 482, Hôpital Saint-Antoine, 184 Rue du Faubourg Saint-Antoine, 75571, Paris Cedex 12, France.);
Abstract	The Sma and Mad related (Smad) family proteins are critical mediators of the transforming growth factor-beta (TGF-beta) superfamily signaling. After TGF-beta-mediated phosphorylation and association with Smad4, Smad2 moves to the nucleus and activates expression of specific genes through cooperative interactions with DNA-binding proteins, including members of the winged-helix family of transcription factors, forkhead activin signal transducer (FAST)-1 and FAST2. TGF-beta has also been described to activate other signaling pathways, such as the c-Jun N-terminal Kinase (JNK) pathway. Here, we show that activation of JNK cascade blocked the ability of Smad2 to mediate TGF-beta-dependent activation of the FAST proteins. This inhibitory activity is mediated through the transcriptional factor c-Jun, which enhances the association of Smad2 with the nuclear transcriptional corepressor TG-interacting factor (TGIF), thereby interfering with the assembly of Smad2 and the coactivator p300 in response to TGF-beta signaling. Interestingly, c-Jun directly binds to the nuclear transcriptional corepressor TGIF and is required for TGIF-mediated repression of Smad2 transcriptional activity. These studies thus reveal a mechanism for suppression of Smad2 signaling pathway by JNK cascade through transcriptional repression.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	11
Volume Number	98
Language	English
Publisher	National Academy of Sciences
Publisher Date	2001-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	DNA-Binding Proteins Metabolism Gene Expression Regulation Homeodomain Proteins MAP Kinase Kinase 4 MAP Kinase Kinase Kinase 1 Mitogen-Activated Protein Kinases Repressor Proteins Signal Transduction Physiology Trans-Activators Transforming Growth Factor Beta Animals COS Cells Cercopithecus Aethiops Genetics Forkhead Transcription Factors JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinase Kinases Protein-Serine-Threonine Kinases Smad2 Protein Transcription Factors Transcription, Genetic Tumor Cells, Cultured Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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