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Aurora-A inactivation causes mitotic spindle pole fragmentation by unbalancing microtubule-generated forces
BACKGROUND: Aurora-A is an oncogenic kinase playing well-documented roles in mitotic spindle organisation. We previously found that Aurora-A inactivation yields the formation of spindles with fragmented poles that can drive chromosome mis-segregation. Here we have addressed the mechanism through whi...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3226445/ https://www.ncbi.nlm.nih.gov/pubmed/22011530 http://dx.doi.org/10.1186/1476-4598-10-131 |
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author | Asteriti, Italia A Giubettini, Maria Lavia, Patrizia Guarguaglini, Giulia |
author_facet | Asteriti, Italia A Giubettini, Maria Lavia, Patrizia Guarguaglini, Giulia |
author_sort | Asteriti, Italia A |
collection | PubMed |
description | BACKGROUND: Aurora-A is an oncogenic kinase playing well-documented roles in mitotic spindle organisation. We previously found that Aurora-A inactivation yields the formation of spindles with fragmented poles that can drive chromosome mis-segregation. Here we have addressed the mechanism through which Aurora-A activity regulates the structure and cohesion of spindle poles. RESULTS: We inactivated Aurora-A in human U2OS osteosarcoma cells either by RNA-interference-mediated silencing or treating cultures with the specific inhibitor MLN8237. We show that mitotic spindle pole fragmentation induced by Aurora-A inactivation is associated with microtubule hyperstabilisation. Silencing of the microtubule-stabilising factor ch-TOG prevents spindle pole fragmentation caused by inactivation of Aurora-A alone and concomitantly reduces the hyperstabilisation of microtubules. Furthermore, decreasing pole-directed spindle forces by inhibition of the Eg5 kinesin, or by destabilisation of microtubule-kinetochore attachments, also prevents pole fragmentation in Aurora-A-inactivated mitoses. CONCLUSIONS: Our findings indicate that microtubule-generated forces are imbalanced in Aurora-A-defective cells and exert abnormal pressure at the level of spindle poles, ultimately causing their fragmentation. This study therefore highlights a novel role of the Aurora-A kinase in regulating the balance between microtubule forces during bipolar spindle assembly. |
format | Online Article Text |
id | pubmed-3226445 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-32264452011-11-30 Aurora-A inactivation causes mitotic spindle pole fragmentation by unbalancing microtubule-generated forces Asteriti, Italia A Giubettini, Maria Lavia, Patrizia Guarguaglini, Giulia Mol Cancer Research BACKGROUND: Aurora-A is an oncogenic kinase playing well-documented roles in mitotic spindle organisation. We previously found that Aurora-A inactivation yields the formation of spindles with fragmented poles that can drive chromosome mis-segregation. Here we have addressed the mechanism through which Aurora-A activity regulates the structure and cohesion of spindle poles. RESULTS: We inactivated Aurora-A in human U2OS osteosarcoma cells either by RNA-interference-mediated silencing or treating cultures with the specific inhibitor MLN8237. We show that mitotic spindle pole fragmentation induced by Aurora-A inactivation is associated with microtubule hyperstabilisation. Silencing of the microtubule-stabilising factor ch-TOG prevents spindle pole fragmentation caused by inactivation of Aurora-A alone and concomitantly reduces the hyperstabilisation of microtubules. Furthermore, decreasing pole-directed spindle forces by inhibition of the Eg5 kinesin, or by destabilisation of microtubule-kinetochore attachments, also prevents pole fragmentation in Aurora-A-inactivated mitoses. CONCLUSIONS: Our findings indicate that microtubule-generated forces are imbalanced in Aurora-A-defective cells and exert abnormal pressure at the level of spindle poles, ultimately causing their fragmentation. This study therefore highlights a novel role of the Aurora-A kinase in regulating the balance between microtubule forces during bipolar spindle assembly. BioMed Central 2011-10-19 /pmc/articles/PMC3226445/ /pubmed/22011530 http://dx.doi.org/10.1186/1476-4598-10-131 Text en Copyright ©2011 Asteriti et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Asteriti, Italia A Giubettini, Maria Lavia, Patrizia Guarguaglini, Giulia Aurora-A inactivation causes mitotic spindle pole fragmentation by unbalancing microtubule-generated forces |
title | Aurora-A inactivation causes mitotic spindle pole fragmentation by unbalancing microtubule-generated forces |
title_full | Aurora-A inactivation causes mitotic spindle pole fragmentation by unbalancing microtubule-generated forces |
title_fullStr | Aurora-A inactivation causes mitotic spindle pole fragmentation by unbalancing microtubule-generated forces |
title_full_unstemmed | Aurora-A inactivation causes mitotic spindle pole fragmentation by unbalancing microtubule-generated forces |
title_short | Aurora-A inactivation causes mitotic spindle pole fragmentation by unbalancing microtubule-generated forces |
title_sort | aurora-a inactivation causes mitotic spindle pole fragmentation by unbalancing microtubule-generated forces |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3226445/ https://www.ncbi.nlm.nih.gov/pubmed/22011530 http://dx.doi.org/10.1186/1476-4598-10-131 |
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