文章基本信息

标题：c-Jun interacts with the corepressor TG-interacting factor (TGIF) to suppress Smad2 transcriptional activity
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作者：Marcia Pessah ; Céline Prunier ; Jacqueline Marais 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2001
卷号：98
期号：11
页码：6198-6203
DOI：10.1073/pnas.101579798
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.