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Papers In Press, published online ahead of print March 19, 2003
Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, Tsukuba, Ibaraki 305-0074
Corresponding Author: sishii{at}rtc.riken.go.jp
Ski is a transcriptional co-repressor, and is involved in the negative regulation of TGF-beta signaling. To understand more fully the role of Ski in TGF-beta signaling, we searched for novel Ski-interacting proteins. The identified C184M protein consists of 189 amino acids and contains the leucine-rich (LR) region. An association between Ski and C184M involving the LR region of C184M and the C-terminal coiled-coil motif of Ski was confirmed by GST pull-down and immunoprecipitation assays. The C184M protein is located in the cytosol, and the C184M and Ski signals co-localized in the cytoplasm when C184M was co-expressed with Ski in CV-1 cells. The cytoplasmic C184M-Ski complex inhibited the nuclear translocation of Smad2. Consistent with this, the activity of promoter containing the Smad-binding sites was repressed by C184M, and the TGF-beta-induced growth inhibition of mink lung Mv1Lu cells was attenuated by the ectopic expression of C184M. Thus, C184M inhibits TGF-beta signaling in concert with Ski. In hepatocytes, which express significant levels of C184M, the Ski signals were found only in the cytoplasm, supporting the notion that C184M forms a complex with Ski in the cytosol.
J. Biol. Chem, 10.1074/jbc.M210855200
Submitted on October 23, 2002
Revised on February 20, 2003
Accepted on March 19, 2003
The Ski-binding protein C184M negatively regulates TGF-beta signaling by sequestering the Smad proteins in the cytoplasm
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