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The p97-cofactor p37 regulates spindle orientation by limiting cortical NuMA recruitment via PP1/Repo-Man

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Defense Thèse de doctorat : Univ. Genève, 2018 - Sc. 5190 - 2018/03/06
Abstract Spindle orientation determines the axis of division and is crucial for cell fate, tissue morphogenesis and for the development of an organism. In animal cells, spindle orientation is regulated by the conserved Gαi/LGN/NuMA complex, which targets the force generator dynein/dynactin to the cortex. Here we show that p37/UBXN2B, a cofactor of the p97 AAA ATPase, regulates spindle orientation in mammalian cells by limiting the levels of cortical NuMA. p37 controls cortical NuMA levels via the phosphatase PP1 and its regulatory subunits Repo-Man, but acts independently of Gαi, the kinase Aurora A, or the phosphatase PP2A. Our data show that in anaphase, when the spindle elongates, PP1-Repo-Man promotes the accumulation of NuMA at the cortex. In metaphase, p37 negatively regulates this function of PP1 resulting in lower cortical NuMA levels and correct spindle orientation.
Keywords Spindle OrientationMitosisCortical pulling forcesNuMAPP1Repo-Man
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URN: urn:nbn:ch:unige-1032001
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LEE, Byung Ho. The p97-cofactor p37 regulates spindle orientation by limiting cortical NuMA recruitment via PP1/Repo-Man. Université de Genève. Thèse, 2018. https://archive-ouverte.unige.ch/unige:103200

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Deposited on : 2018-03-26

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