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

Oncogene volume 19, pages 5997–6006 (2000)Cite this article

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 α-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.

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Acknowledgements

We thank Drs N Tokai, M Ohsugi and T Yamamoto for the kind gift of pME-Kid plasmid and anti-Kid antibody. A Germani is the recipient of a TMR fellowship from European Community. H Bruzzoni-Giovanelli was the recipient of a grant from the French Government and from Conicyt Uruguay and Eli Lilly International Foundtaion. This work was partially supported by grants from ‘Association pour la Recherche Contre le Cancer (ARC)’, ‘La Ligue Contre le Cancer’ and ECOS program, to F Calvo and ARC to N Varin-Blank.

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Author notes

  1. Antonia Germani and Heriberto Bruzzoni-Giovanelli: A Germani and H Bruzzoni-Giovanelli contributed equally to this work

  2. Nadine Varin-Blank and Fabien Calvo: N Varin-Blank and F Calvo are co-senior authors

Authors and Affiliations

  1. Unité 363 INSERM. Institut Cochin de Génétique Moléculaire, Hôpital Cochin, 27, rue Faubourg Saint Jacques, Paris, 75014, France

    Antonia Germani, Sylvie Gisselbrecht & Nadine Varin-Blank

  2. Laboratoire de Pharmacologie Expérimentale et Clinique INSERM EP-9932, Institute de Génétique Moléculaire, Hôpital Saint-Louis, 27, rue Juliette Dodu, Paris, 75010, France

    Heriberto Bruzzoni-Giovanelli, Arlette Fellous & Fabien Calvo

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  1. Antonia Germani
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Germani, A., Bruzzoni-Giovanelli, H., Fellous, A. et al. SIAH-1 interacts with α-tubulin and degrades the kinesin Kid by the proteasome pathway during mitosis. Oncogene 19, 5997–6006 (2000). https://doi.org/10.1038/sj.onc.1204002

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