SIAH-1 interacts with alpha-tubulin and degrades the kinesin Kid by the proteasome pathway during mitosis

Oncogene. 2000 Dec 7;19(52):5997-6006. doi: 10.1038/sj.onc.1204002.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle
  • Cysteine Endopeptidases / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Fluorescent Antibody Technique
  • Gene Expression Regulation
  • Humans
  • Kinesins / genetics
  • Kinesins / metabolism*
  • Mitosis*
  • Multienzyme Complexes / metabolism*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Precipitin Tests
  • Proteasome Endopeptidase Complex
  • Protein Binding
  • Protein Processing, Post-Translational*
  • Protein Structure, Tertiary
  • Sequence Deletion / genetics
  • Substrate Specificity
  • Transfection
  • Tubulin / genetics
  • Tubulin / metabolism*
  • Tumor Cells, Cultured
  • Two-Hybrid System Techniques
  • Ubiquitin-Protein Ligases
  • Ubiquitins / metabolism

Substances

  • DNA-Binding Proteins
  • KIF22 protein, human
  • Multienzyme Complexes
  • Nuclear Proteins
  • Tubulin
  • Ubiquitins
  • Ubiquitin-Protein Ligases
  • seven in absentia proteins
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • Kinesins