Nuclear retention of the tumor suppressor cPML by the homeodomain protein TGIF restricts TGF-beta signaling.

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.
Mesh Terms:
Animals, COS Cells, Cell Nucleus, Cells, Cultured, Cercopithecus aethiops, Dogs, Down-Regulation, Epithelial Cells, Homeodomain Proteins, Humans, Mice, Neoplasm Proteins, Nuclear Proteins, Phosphorylation, Protein Binding, Proto-Oncogene Proteins c-jun, Repressor Proteins, Signal Transduction, Smad2 Protein, Transcription Factors, Transcription, Genetic, Transforming Growth Factor beta, Tumor Suppressor Proteins
Mol. Cell
Date: Aug. 01, 2006
Download Curated Data For This Publication
145408
Switch View:
  • Interactions 10