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Excess TPX2 Interferes with Microtubule Disassembly and Nuclei Reformation at Mitotic Exit.
Naso, Francesco D; Sterbini, Valentina; Crecca, Elena; Asteriti, Italia A; Russo, Alessandra D; Giubettini, Maria; Cundari, Enrico; Lindon, Catherine; Rosa, Alessandro; Guarguaglini, Giulia.
Afiliación
  • Naso FD; Institute of Molecular Biology and Pathology, National Research Council of Italy, c/o Sapienza University of Rome, Via degli Apuli 4, 00185 Rome, Italy.
  • Sterbini V; Institute of Molecular Biology and Pathology, National Research Council of Italy, c/o Sapienza University of Rome, Via degli Apuli 4, 00185 Rome, Italy.
  • Crecca E; Institute of Molecular Biology and Pathology, National Research Council of Italy, c/o Sapienza University of Rome, Via degli Apuli 4, 00185 Rome, Italy.
  • Asteriti IA; Institute of Molecular Biology and Pathology, National Research Council of Italy, c/o Sapienza University of Rome, Via degli Apuli 4, 00185 Rome, Italy.
  • Russo AD; Institute of Molecular Biology and Pathology, National Research Council of Italy, c/o Sapienza University of Rome, Via degli Apuli 4, 00185 Rome, Italy.
  • Giubettini M; CrestOptics S.p.A., Via di Torre Rossa 66, 00165 Rome, Italy.
  • Cundari E; Center for Life Nano Science, Istituto Italiano di Tecnologia, Viale Regina Elena 291, 00161 Rome, Italy.
  • Lindon C; Institute of Molecular Biology and Pathology, National Research Council of Italy, c/o Sapienza University of Rome, Via degli Apuli 4, 00185 Rome, Italy.
  • Rosa A; Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK.
  • Guarguaglini G; Center for Life Nano Science, Istituto Italiano di Tecnologia, Viale Regina Elena 291, 00161 Rome, Italy.
Cells ; 9(2)2020 02 06.
Article en En | MEDLINE | ID: mdl-32041138
The microtubule-associated protein TPX2 is a key mitotic regulator that contributes through distinct pathways to spindle assembly. A well-characterised function of TPX2 is the activation, stabilisation and spindle localisation of the Aurora-A kinase. High levels of TPX2 are reported in tumours and the effects of its overexpression have been investigated in cancer cell lines, while little is known in non-transformed cells. Here we studied TPX2 overexpression in hTERT RPE-1 cells, using either the full length TPX2 or a truncated form unable to bind Aurora-A, to identify effects that are dependent-or independent-on its interaction with the kinase. We observe significant defects in mitotic spindle assembly and progression through mitosis that are more severe when overexpressed TPX2 is able to interact with Aurora-A. Furthermore, we describe a peculiar, and Aurora-A-interaction-independent, phenotype in telophase cells, with aberrantly stable microtubules interfering with nuclear reconstitution and the assembly of a continuous lamin B1 network, resulting in daughter cells displaying doughnut-shaped nuclei. Our results using non-transformed cells thus reveal a previously uncharacterised consequence of abnormally high TPX2 levels on the correct microtubule cytoskeleton remodelling and G1 nuclei reformation, at the mitosis-to-interphase transition.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Núcleo Celular / Proteínas de Ciclo Celular / Proteínas Asociadas a Microtúbulos / Microtúbulos / Mitosis Límite: Humans Idioma: En Revista: Cells Año: 2020 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Núcleo Celular / Proteínas de Ciclo Celular / Proteínas Asociadas a Microtúbulos / Microtúbulos / Mitosis Límite: Humans Idioma: En Revista: Cells Año: 2020 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Suiza