Abstract
The Sloan Kettering Virus (Ski) family of nuclear oncoproteins represses transforming growth factor-beta (TGF-beta) signaling through inhibition of transcriptional activity of Smad proteins. Here, we report the discovery of a new functional Smad suppressing element on chromosome 18 (Fussel-18). Fussel-18 encodes for a protein of 297 amino acids sharing characteristic structural features, significant homology and similar genomic organization with the homolog Ski family members, Ski and Ski-related novel sequence (Sno). In contrast to Ski and Sno, which are ubiquitously expressed in human tissues, in situ hybridization, RT-PCR, Western blot and immunohistochemistry revealed a highly specific expression pattern for Fussel-18 in neuronal tissues, especially in the cerebellum, the spinal cord and dorsal root ganglia, during both embryogenesis and adult stage. Functionally, we determined interaction of Fussel-18 with Smad 2 and Smad 3 together with an inhibitory activity on TGF-beta signaling. Fussel-18 is the first example of a Smad-binding protein with a highly restricted expression pattern within the nervous system.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Motifs
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Amino Acid Sequence
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Animals
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Bone Morphogenetic Proteins / genetics
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Bone Morphogenetic Proteins / metabolism
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Cell Line
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Cell Line, Tumor
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Chromosomes, Human, Pair 18*
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Cloning, Molecular*
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Conserved Sequence
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Embryonic Development
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Gene Expression
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Humans
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Intracellular Signaling Peptides and Proteins
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Mice
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Molecular Sequence Data
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Molecular Weight
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Nerve Tissue / metabolism*
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Nuclear Proteins / chemistry
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Oncogene Proteins / chemistry
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Oncogene Proteins / genetics
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Oncogene Proteins / metabolism
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Protein Structure, Tertiary
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Proto-Oncogene Proteins / chemistry
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins / metabolism*
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RNA, Messenger / metabolism
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Sequence Homology, Amino Acid
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Smad2 Protein / metabolism
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Smad3 Protein / metabolism
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Transforming Growth Factor beta / antagonists & inhibitors
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Transforming Growth Factor beta / genetics
Substances
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Bone Morphogenetic Proteins
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Intracellular Signaling Peptides and Proteins
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Nerve Tissue Proteins
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Nuclear Proteins
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Oncogene Proteins
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Proto-Oncogene Proteins
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RNA, Messenger
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SKIL protein, human
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SKOR2 protein, human
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Smad2 Protein
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Smad3 Protein
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Transforming Growth Factor beta