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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2003-5-26
pubmed:abstractText
Ski is a transcriptional co-repressor and is involved in the negative regulation of tumor growth factor-beta (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 region. An association between Ski and C184M involving the leucine-rich region of C184M and the C-terminal coiled-coil motif of Ski was confirmed by glutathione S-transferase pull-down and immunoprecipitation assays. The C184M protein is located in the cytosol, and the C184M and Ski signals are 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
20133-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12646588-Animals, pubmed-meshheading:12646588-Cell Line, pubmed-meshheading:12646588-Cell Nucleus, pubmed-meshheading:12646588-Cytoplasm, pubmed-meshheading:12646588-DNA-Binding Proteins, pubmed-meshheading:12646588-Humans, pubmed-meshheading:12646588-Mice, pubmed-meshheading:12646588-Mice, Inbred C57BL, pubmed-meshheading:12646588-Nuclear Proteins, pubmed-meshheading:12646588-Nuclear Receptor Coactivators, pubmed-meshheading:12646588-Protein Binding, pubmed-meshheading:12646588-Protein Transport, pubmed-meshheading:12646588-Signal Transduction, pubmed-meshheading:12646588-Smad Proteins, pubmed-meshheading:12646588-Trans-Activators, pubmed-meshheading:12646588-Transcription Factors, pubmed-meshheading:12646588-Transforming Growth Factor beta, pubmed-meshheading:12646588-Two-Hybrid System Techniques
pubmed:year
2003
pubmed:articleTitle
The Ski-binding protein C184M negatively regulates tumor growth factor-beta signaling by sequestering the Smad proteins in the cytoplasm.
pubmed:affiliation
Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, 3-1-1 Koyadai, Ibaraki 305-0074, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't