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Intracellular TIAF1 self‐association induces apoptosis
Author(s) -
Chang NanShan
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.526.1
Subject(s) - apoptosis , microbiology and biotechnology , smad , cytoplasm , small interfering rna , biology , intracellular , signal transducing adaptor protein , signal transduction , cell culture , transfection , biochemistry , genetics
TIAF1 is a small TGF‐beta1‐induced factor, which supports fibroblast growth, T helper cell activation and effect on allograft organ rejection, and probably induces regulator TREG cell differentiation. However, overexpressed TIAF1 induces apoptosis in monocytic and epithelial cells and non‐fibroblasts. Here, we demonstrate that TIAF1 self‐association leads to apoptosis. When cells were overexpressed with CFP‐TIAF1 and YFP‐TIAF1, TIAF1 underwent self‐association and the cells died. Also, TGF‐beta enhances the self‐association for causing apoptosis in TGF‐beta‐sensitive normal epithelial cells. Smad4, an adaptor in the TGF‐beta signaling, binds TIAF1 and blocks the apoptosis. Transiently overexpressed TIAF1 sequesters endogenous Smad proteins in the cytoplasm, and blocks the activation of promoter element driven by Smad proteins. Small interfering RNA‐targeting TIAF1 augments the apoptotic function of overexpressed Smad4. Together, self‐association of TIAF1 induces apoptosis, and that Smad4 interrupts the event.