The Fcp1-Wee1-Cdk1 axis affects spindle assembly checkpoint robustness and sensitivity to antimicrotubule cancer drugs (Articolo in rivista)

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Label
  • The Fcp1-Wee1-Cdk1 axis affects spindle assembly checkpoint robustness and sensitivity to antimicrotubule cancer drugs (Articolo in rivista) (literal)
Anno
  • 2015-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1038/cdd.2015.13 (literal)
Alternative label
  • R Visconti, R Della Monica, L Palazzo, F D'Alessio, M Raia, S Improta, MR Villa, L Del Vecchio, D Grieco (2015)
    The Fcp1-Wee1-Cdk1 axis affects spindle assembly checkpoint robustness and sensitivity to antimicrotubule cancer drugs
    in Cell death and differentiation
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • R Visconti, R Della Monica, L Palazzo, F D'Alessio, M Raia, S Improta, MR Villa, L Del Vecchio, D Grieco (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url
  • http://www.nature.com/cdd/journal/vaop/ncurrent/full/cdd201513a.html (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • IEOS, CNR, S. Pansini 5, Naples 80131, Italy CEINGE Biotecnologie Avanzate, Gaetano Salvatore 486, Naples 80145, Italy DMMBM, University of Naples \"Federico II\",S. Pansini 5, Naples 80131, Italy Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK Division of Hematology, PO San Gennaro, ASLNA1 Centro, Naples 80136, Italy (literal)
Titolo
  • The Fcp1-Wee1-Cdk1 axis affects spindle assembly checkpoint robustness and sensitivity to antimicrotubule cancer drugs (literal)
Abstract
  • To grant faithful chromosome segregation, the spindle assembly checkpoint (SAC) delays mitosis exit until mitotic spindle assembly. An exceedingly prolonged mitosis, however, promotes cell death and by this means antimicrotubule cancer drugs (AMCDs), that impair spindle assembly, are believed to kill cancer cells. Despite malformed spindles, cancer cells can, however, slip through SAC, exit mitosis prematurely and resist killing. We show here that the Fcp1 phosphatase and Wee1, the cyclin B-dependent kinase (cdk) 1 inhibitory kinase, play a role for this slippage/resistance mechanism. During AMCD-induced prolonged mitosis, Fcp1-dependent Wee1 reactivation lowered cdk1 activity, weakening SAC-dependent mitotic arrest and leading to mitosis exit and survival. Conversely, genetic or chemical Wee1 inhibition strengthened the SAC, further extended mitosis, reduced antiapoptotic protein Mcl-1 to a minimum and potentiated killing in several, AMCD-treated cancer cell lines and primary human adult lymphoblastic leukemia cells. Thus, the Fcp1-Wee1-Cdk1 (FWC) axis affects SAC robustness and AMCDs sensitivity. (literal)
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