Cell division and cell survival in the absence of survivin
Open Access
- 11 October 2004
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 101 (42), 15100-15105
- https://doi.org/10.1073/pnas.0406665101
Abstract
The survivin protein contains structural features of the inhibitor of apoptosis protein family. Previous studies have suggested that survivin is essential for cell survival because it counteracts an otherwise constitutive propensity to apoptosis during mitosis. In addition, survivin appears to be a component of the chromosomal passenger protein complex that participates in multiple facets of cell division. Here we report that euploid human cells do not die in the absence of survivin. Instead, depletion of survivin caused defects in cell division, followed by an arrest of DNA synthesis due to activation of a checkpoint involving the tumor suppressor protein p53. During anaphase mitosis in survivin-deficient cells, sister chromatids disjoined normally, but one or more of the sister chromatids frequently lagged behind the main mass of segregating chromosomes, probably because of merotelic kinetochore attachments. Survivin-deficient cells initiated but failed to complete cytokinesis, apparently because the spindle midzone and midbody microtublues were absent during late mitosis. The abnormalities of both chromosome segregation and cytokinesis could be attributed to a defect in the chromosomal passenger protein complex, with a consequent mislocalization of the kinesin-like motor protein MKLP-1 playing a more immediate role in the microtubule abnormalities. Depletion of another chromosomal passenger protein, aurora-B, recapitulated the survivin RNA interference phenotypes. We conclude that survivin can be essential for the proliferation of normal human cells by virtue of its contributions to accurate sister chromatid segregation and assembly/stabilization of microtubules in late mitosis. However, the protein is not inevitably required for the survival of normal cells.Keywords
This publication has 28 references indexed in Scilit:
- Cell cycle progression after cleavage failureThe Journal of cell biology, 2004
- Correcting improper chromosome–spindle attachments during cell divisionNature, 2004
- Survivin Loss in Thymocytes Triggers p53-mediated Growth Arrest and p53-independent Cell DeathThe Journal of Experimental Medicine, 2004
- Survivin is required for stable checkpoint activation in taxol-treated HeLa cellsJournal of Cell Science, 2003
- Validating survivin as a cancer therapeutic targetNature Reviews Cancer, 2003
- Short RNA duplexes produced by hydrolysis with Escherichia coli RNase III mediate effective RNA interference in mammalian cellsProceedings of the National Academy of Sciences, 2002
- Evidence that the Ipl1-Sli15 (Aurora Kinase-INCENP) Complex Promotes Chromosome Bi-orientation by Altering Kinetochore-Spindle Pole ConnectionsCell, 2002
- Tetraploid State Induces p53-dependent Arrest of Nontransformed Mammalian Cells in G1Molecular Biology of the Cell, 2001
- Regulation of the G2/M transition by p53Oncogene, 2001
- Regulation of apoptosis at cell division by p34 cdc2 phosphorylation of survivinProceedings of the National Academy of Sciences, 2000