SIAH-1 interacts with alpha-tubulin and degrades the kinesin Kid by the proteasome pathway during mitosis.
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.
Pubmed ID: 11146551 RIS Download
Cell Cycle | Cysteine Endopeptidases | DNA-Binding Proteins | Fluorescent Antibody Technique | Gene Expression Regulation | Humans | Kinesin | Mitosis | Multienzyme Complexes | Nuclear Proteins | Precipitin Tests | Proteasome Endopeptidase Complex | Protein Binding | Protein Processing, Post-Translational | Protein Structure, Tertiary | Sequence Deletion | Substrate Specificity | Transfection | Tubulin | Tumor Cells, Cultured | Two-Hybrid System Techniques | Ubiquitin-Protein Ligases | Ubiquitins