Non-centrosomal TPX2-dependent regulation of the Aurora A kinase: functional implications for healthy and pathological cell division

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• dc.contributor.author Garrido, Georginaca
• dc.contributor.author Vernos, Isabelle, 1959-ca
• dc.date.accessioned 2016-06-01T14:35:17Z
• dc.date.available 2016-06-01T14:35:17Z
• dc.date.issued 2016
• dc.description.abstract Aurora A has been extensively characterized as a centrosomal kinase with essential functions during cell division including centrosome maturation and separation and spindle assembly. However, Aurora A localization is not restricted to the centrosomes and compelling evidence support the existence of specific mechanisms of activation and functions for non-centrosomal Aurora A in the dividing cell. It has been now well established that spindle assembly involves an acentrosomal RanGTP-dependent pathway that triggers microtubule assembly and organization in the proximity of the chromosomes whether centrosomes are present or not. The mechanism involves the regulation of a number of NLS-containing proteins, generically called SAFS (Spindle Assembly Factors) that exert their functions upon release from karyopherins by RanGTP. One of them, the nuclear protein TPX2 interacts with and activates Aurora A upon release from importins by RanGTP. This basic mechanism triggers the activation of Aurora A in the proximity of the chromosomes potentially translating the RanGTP signaling gradient centered on the chromosome into an Aurora A phosphorylation network. Here, we will review our current knowledge on the RanGTP-dependent TPX2 activation of Aurora A away from centrosomes: from the mechanism of activation and its functional consequences on the kinase stability and regulation to its roles in spindle assembly and cell division. We will then focus on the substrates of the TPX2-activated Aurora A having a role in microtubule nucleation, stabilization, and organization. Finally, we will briefly discuss the implications of the use of Aurora A inhibitors in anti-tumor therapies in the light of its functional interaction with TPX2.ca
• dc.description.sponsorship Work in the Vernos lab was supported by the Spanish ministry grants BFU2009-10202 and BFU2012-37163. We also acknowledge support of the Spanish Ministry of Economy and Competitiveness, “Centro de Excelencia Severo Ochoa 2013-2017,” SEV-2012-0208.
• dc.format.mimetype application/pdfca
• dc.identifier.citation Garrido G, Vernos I. Non-centrosomal TPX2-dependent regulation of the Aurora A kinase: functional implications for healthy and pathological cell division. Frontiers in oncology. 2016; 6: 88. DOI 10.3389/fonc.2016.00088ca
• dc.identifier.doi http://dx.doi.org/10.3389/fonc.2016.00088
• dc.identifier.issn 2234-943X
• dc.identifier.uri http://hdl.handle.net/10230/26796
• dc.language.iso engca
• dc.publisher Frontiersca
• dc.relation.ispartof Frontiers in oncology. 2016; 6: 88
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2009-10202
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2012-37163
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SEV-2012-0208
• dc.rights © 2016 Garrido and Vernos. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.ca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/ca
• dc.subject.keyword Aurora A kinase
• dc.subject.keyword RanGTP
• dc.subject.keyword TPX2
• dc.subject.keyword Cell division
• dc.subject.keyword Importin
• dc.subject.keyword Microtubule
• dc.subject.keyword Phosphorylation
• dc.subject.keyword Spindle
• dc.subject.other Cèl·lules Proliferacióca
• dc.title Non-centrosomal TPX2-dependent regulation of the Aurora A kinase: functional implications for healthy and pathological cell divisionca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersionca