Abstract:
:Here we investigate the role of the control of apoptosis in normal cell division. We show that interference with the expression or function of the apoptosis inhibitor survivin causes caspase-dependent cell death in the G2/M phase of the cell cycle, and a cell-division defect characterized by centrosome dysregulation, multipolar mitotic spindles and multinucleated, polyploid cells. Use of a dominant-negative survivin mutant or antisense survivin complementary DNA disrupts a supramolecular assembly of survivin, caspase-3 and the cyclin-dependent-kinase inhibitor p21Waf1/Cip1 within centrosomes, and results in caspase-dependent cleavage of p21. Polyploidy induced by survivin antagonists is accentuated in p21-deficient cells, and corrected by exogenous expression of p21. These findings show that control of apoptosis and preservation of p21 integrity within centrosomes by survivin are required for normal mitotic progression.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Li F,Ackermann EJ,Bennett CF,Rothermel AL,Plescia J,Tognin S,Villa A,Marchisio PC,Altieri DCdoi
10.1038/70242keywords:
subject
Has Abstractpub_date
1999-12-01 00:00:00pages
461-6issue
8eissn
1465-7392issn
1476-4679journal_volume
1pub_type
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