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.
Germani
A
A
Unité 363 INSERM, Institut Cochin de Génétique Moléculaire, H pital Cochin, Paris, France.
Bruzzoni-Giovanelli
H
H
Fellous
A
A
Gisselbrecht
S
S
Varin-Blank
N
N
Calvo
F
F
D002453:Cell Cycle; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis; D009097:Multienzyme Complexes / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011233:Precipitin Tests; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion / Q000235:genetics; D013379:Substrate Specificity; D014162:Transfection; D014404:Tubulin / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism; D000098563:Seven in Absentia Proteins
D004268:DNA-Binding Proteins; C098764:KIF22 protein, human; D009097:Multienzyme Complexes; D009687:Nuclear Proteins; D014404:Tubulin; D014452:Ubiquitins; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D016547:Kinesins