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Optineurine, un nouveau régulateur de la mitose

Abstract : Optineurin ("Optic neuropathy-inducing", Optn) is a protein ubiquitously expressed in vertebrates. This protein is involved in several cellular physiological processes such as vesicular trafficking, protein secretion, innate immune response and bacterial autophagy. My thesis work led to the identification of Optn as a negative regulator of Polo-like kinase 1 (Plk1), a kinase that participates in regulating each step of mitosis from prophase to cytokinesis. We have shown that Plk1 phosphorylates Optn at serine 177 during the G2/M transition, leading to the dissociation of Optn from the Golgi apparatus and its accumulation into the nucleus. Interestingly, both events are required for the negative regulation of Plk1 by the phosphatase complex MYPT1-PP1β during mitosis. These results indicate a negative feedback mechanism by which Plk1 modulates Optn localization in order to regulate its own activity. Consistently, Plk1 activity is sustained in Optn-deficient cells, inducing major mitotic anomalies, such as defects of chromosome segregation and abscission failures and eventually multi-nucleated cells. Altogether, our results uncover a cell cycle regulatory function for Optn, a protein that have also been linked to the development of several pathologies such as glaucoma, amyotrophic lateral sclerosis and Paget's disease of bone
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Submitted on : Friday, June 7, 2013 - 12:07:15 PM
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  • HAL Id : tel-00831584, version 1


David Kachaner. Optineurine, un nouveau régulateur de la mitose. Biochimie, Biologie Moléculaire. Université Pierre et Marie Curie - Paris VI, 2012. Français. ⟨NNT : 2012PAO66221⟩. ⟨tel-00831584⟩



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