Control of Aurora-A stability via its interaction with TPX2 (Articolo in rivista)

Type
Label
  • Control of Aurora-A stability via its interaction with TPX2 (Articolo in rivista) (literal)
Anno
  • 2010-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1242/jcs.075457 (literal)
Alternative label
  • Giubettini M, Asteriti IA, Scrofani J, De Luca M, Lindon C, Lavia P, Guarguaglini G. (2010)
    Control of Aurora-A stability via its interaction with TPX2
    in Journal of cell science (Online)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Giubettini M, Asteriti IA, Scrofani J, De Luca M, Lindon C, Lavia P, 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, c/o Sapienza University of Rome, Via degli Apuli 4, 00185, Rome, Italy University of Cambridge, Department of Genetics, Downing Street, Cambridge, UK CB2 3EH (literal)
Titolo
  • Control of Aurora-A stability via its interaction with TPX2 (literal)
Abstract
  • The Aurora-A kinase has well-established roles in spindle assembly and function and is frequently overexpressed in tumours. Its abundance is cell cycle regulated, with a peak in G2 and M phases, followed by regulated proteolysis at the end of mitosis. The microtubule-binding protein TPX2 plays a major role in regulating the activity and localisation of Aurora-A in mitotic cells. Here, we report a novel regulatory role of TPX2 and show that it protects Aurora-A from degradation both in interphase and in mitosis in human cells. Specifically, Aurora-A levels decrease in G2 and prometaphase cells silenced for TPX2, whereas degradation of Aurora-A is impaired in telophase cells overexpressing the Aurora-A-binding region of TPX2. The decrease in Aurora-A in TPX2-silenced prometaphases requires proteasome activity and the Cdh1 activator of the APC/C ubiquitin ligase. Reintroducing either full-length TPX2, or the Aurora-A-binding region of TPX2, but not a truncated TPX2 mutant lacking the Aurora-A-interaction domain, restores Aurora-A levels in TPX2-silenced prometaphases. The control by TPX2 of Aurora-A stability is independent of its ability to activate Aurora-A and to localise it to the spindle. These results highlight a novel regulatory level impinging on Aurora-A and provide further evidence for the central role of TPX2 in regulation of Aurora-A. (literal)
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