| Literature DB >> 16916642 |
Su Ryeon Seo1, Nathalie Ferrand, Nourdine Faresse, Céline Prunier, Lucile Abécassis, Marcia Pessah, Marie-Francoise Bourgeade, Azeddine Atfi.
Abstract
The homeodomain protein TGIF has been implicated in the negative regulation of TGF-beta signaling. In this study, we report an unexpected role of TGIF in the inhibition of Smad2 phosphorylation, which occurs by a mechanism independent of its association with Smad2. This inhibitory function of TGIF is executed in concert with c-Jun, which facilitates the interaction of TGIF with cPML, resulting in the nuclear sequestration of cPML and the disruption of the cPML-SARA complex. Notably, knockdown of TGIF by siRNA caused increased association of cPML with SARA and cytoplasmic accumulation of cPML. Furthermore, c-Jun(-/-) fibroblasts exhibit enhanced association of cPML with SARA. c-Jun(-/-) fibroblasts also lose their sensitivity to TGIF-mediated disruption of the cPML-SARA complex and of nuclear sequestration of cPML. We suggest that the interaction of TGIF with cPML through c-Jun may negatively regulate TGF-beta signaling through controlling the localization of cPML and, consequently, the assembly of the cPML-SARA complex.Entities:
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Year: 2006 PMID： 16916642 DOI： 10.1016/j.molcel.2006.06.018
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970