Pleiotropic cell-division defects and apoptosis induced by interference with survivin function.

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 Biol

journal_title

Nature cell biology

authors

Li F,Ackermann EJ,Bennett CF,Rothermel AL,Plescia J,Tognin S,Villa A,Marchisio PC,Altieri DC

doi

10.1038/70242

keywords:

subject

Has Abstract

pub_date

1999-12-01 00:00:00

pages

461-6

issue

8

eissn

1465-7392

issn

1476-4679

journal_volume

1

pub_type

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