Modulation of cell division by an early mitotic inhibitor...

C - Chemistry – Metallurgy – 12 – N

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C12N 5/00 (2006.01) C07K 14/00 (2006.01) C07K 14/46 (2006.01) C12N 5/02 (2006.01)

Patent

CA 2448360

Emi1 regulates progression through early mitosis by preventing premature APC activation. Depleting Emi1 from cycling cells strongly delays cyclin B accumulation and mitotic entry, while expression of a stabilized form of Emi1 stabilizes APC substrates and causes a mitotic block. Emi1 binds the APC activators Cdc20 and Cdh1 and inhibits APC activation by Cdc20 or Cdh1. Hence, products that modulate the expression and/or activity of Emi1 have a therapeutic effect in the treatment of cancer, leukemia, solid tumors, chronic or acute inflammatory disease, restenosis, diabetes, neurological disorders, arthritis and osteoporosis, among other indications.

Selon la présente invention, un inhibiteur de mitose précoce Emi1 régule la progression d'une mitose précoce en empêchant une activation prématurée du complexe responsable du déclenchement de l'anaphase (APC). Le fait de retirer l'inhibiteur Emi1 des cellules du cycle cellulaire retarde fortement l'accumulation des cyclines B et l'entrée mitotique, alors que l'expression d'une forme stabilisée de Emi1 stabilise les substrats du complexe APC et provoque un bloc mitotique. L'inhibiteur Emi1 se lie aux activateurs Cdc20 et Cdh1 du complexe APC et inhibe l'activation du complexe APC à l'aide de Cdc20 ou de Cdh1. De ce fait, les produits qui modulent l'expression et/ou l'activité de Emi1 présentent un effet thérapeutique notamment dans le traitement du cancer, de la leucémie, de tumeurs solides, de maladies chroniques ou inflammatoires aiguës, de la resténose, des diabètes, de troubles neurologiques, de l'arthrite et de l'ostéoporose.

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