Aurora-A inactivation causes mitotic spindle pole fragmentation by unbalancing microtubule-generated forces (Articolo in rivista)

Type
Label
  • Aurora-A inactivation causes mitotic spindle pole fragmentation by unbalancing microtubule-generated forces (Articolo in rivista) (literal)
Anno
  • 2011-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1186/1476-4598-10-131 (literal)
Alternative label
  • Asteriti IA, Giubettini M, Lavia P and Guarguaglini G. (2011)
    Aurora-A inactivation causes mitotic spindle pole fragmentation by unbalancing microtubule-generated forces
    in Molecular cancer
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Asteriti IA, Giubettini M, Lavia P and Guarguaglini G. (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Institute of Molecular Biology and Pathology, CNR (literal)
Titolo
  • Aurora-A inactivation causes mitotic spindle pole fragmentation by unbalancing microtubule-generated forces (literal)
Abstract
  • 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. (literal)
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