Abstract
SIAH-1, a human homologue of the Drosophila seven in absentia (Sina), has been implicated in ubiquitin-mediated proteolysis of different target proteins through its N-terminal RING finger domain. SIAH-1 is also induced during p53-mediated apoptosis. Furthermore, SIAH-1-transfected breast cancer cell line MCF-7 exhibits an altered mitotic process resulting in multinucleated giant cells. Now, using the two-hybrid system, we identified two new SIAH interacting proteins: Kid (kinesin like DNA binding protein) and alpha-tubulin. We demonstrate that SIAH is involved in the degradation of Kid via the ubiquitin-proteasome pathway. Our results suggest that SIAH-1 but not its N-terminal deletion mutant, affects the mitosis by an enhanced reduction of kinesin levels. Our results imply, for the first time, SIAH-1 in regulating the degradation of proteins directly implicated in the mitotic process.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Cycle
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Cysteine Endopeptidases / metabolism*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Fluorescent Antibody Technique
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Gene Expression Regulation
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Humans
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Kinesins / genetics
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Kinesins / metabolism*
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Mitosis*
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Multienzyme Complexes / 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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Precipitin Tests
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Proteasome Endopeptidase Complex
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Protein Binding
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Protein Processing, Post-Translational*
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Protein Structure, Tertiary
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Sequence Deletion / genetics
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Seven in Absentia Proteins
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Substrate Specificity
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Transfection
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Tubulin / genetics
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Tubulin / metabolism*
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Tumor Cells, Cultured
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Two-Hybrid System Techniques
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Ubiquitin-Protein Ligases
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Ubiquitins / metabolism
Substances
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DNA-Binding Proteins
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KIF22 protein, human
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Multienzyme Complexes
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Nuclear Proteins
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Tubulin
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Ubiquitins
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Ubiquitin-Protein Ligases
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Seven in Absentia Proteins
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Cysteine Endopeptidases
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Proteasome Endopeptidase Complex
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Kinesins