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.

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. - In: CELLS. - ISSN 2073-4409. - 9:2(2020), pp. 1-21. [10.3390/cells9020374]

Excess TPX2 interferes with microtubule disassembly and nuclei reformation at mitotic exit

Naso, Francesco D;Crecca, Elena;Rosa, Alessandro;
2020

Abstract

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.
2020
TPX2; mitosis; nuclear envelope; spindle
01 Pubblicazione su rivista::01a Articolo in rivista
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. - In: CELLS. - ISSN 2073-4409. - 9:2(2020), pp. 1-21. [10.3390/cells9020374]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1367089
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