PMID:12805209

Citation	Lens, SM, Wolthuis, RM, Klompmaker, R, Kauw, J, Agami, R, Brummelkamp, T, Kops, G and Medema, RH (2003) Survivin is required for a sustained spindle checkpoint arrest in response to lack of tension. EMBO J. 22:2934-47
Abstract	Genetic evidence is mounting that survivin plays a crucial role in mitosis, but its exact role in human cell division remains elusive. We show that mammalian cells lacking survivin are unable to align their chromosomes, fail to recruit Aurora B to kinetochores and become polyploid at a very high frequency. Survivin-depleted cells enter mitosis with normal kinetics, but are delayed in prometaphase in a BubR1/Mad2-dependent fashion. Nonetheless, these cells exit mitosis prior to completion of chromosome congression and without sister chromatid segregation, indicating that the spindle assembly checkpoint is not fully functional. Indeed, in survivin-depleted cells, BubR1 and Mad2 are prematurely displaced from kinetochores, yet no tension is generated at kinetochores. Importantly, these cells fail to respond to drugs that prevent tension, but do arrest in mitosis after depolymerization of the mitotic spindle. This demonstrates that survivin is not required for initial checkpoint activation, or for sustained checkpoint activation by loss of microtubules. However, stable association of BubR1 to kinetochores and sustained checkpoint signalling in response to lack of tension crucially depend on survivin.
Links	PubMed PMC162159 Online version:10.1093/emboj/cdg307
Keywords	Animals; Antineoplastic Agents, Phytogenic/metabolism; Calcium-Binding Proteins/genetics; Calcium-Binding Proteins/metabolism; Cell Cycle Proteins/genetics; Cell Cycle Proteins/metabolism; Cell Line; Chromosomes, Human/metabolism; Chromosomes, Mammalian/metabolism; Cysteine Proteinase Inhibitors/metabolism; Genes, Reporter; Humans; Inhibitor of Apoptosis Proteins; Mice; Microtubule-Associated Proteins/genetics; Microtubule-Associated Proteins/metabolism; Mitosis/physiology; Mitotic Spindle Apparatus/metabolism; Neoplasm Proteins; Paclitaxel/metabolism; Protein Kinases/genetics; Protein Kinases/metabolism; Protein-Serine-Threonine Kinases/genetics; Protein-Serine-Threonine Kinases/metabolism; Pyrimidines/metabolism; Recombinant Fusion Proteins/genetics; Recombinant Fusion Proteins/metabolism; Repressor Proteins; Signal Transduction/physiology; Spectrin/genetics; Spectrin/metabolism; Stress, Mechanical; Thiones/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:A2SUH6	involved_in	GO:0007094: mitotic spindle assembly checkpoint	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:A2SUH6	involved_in	GO:0031536: positive regulation of exit from mitosis	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:A2SUH6	involved_in	GO:0000281: mitotic cytokinesis	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:A2SUH6	involved_in	GO:0051301: cell division	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:A2SUH6	involved_in	GO:0051303: establishment of chromosome localization	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:BIRC5	involved_in	GO:0051303: establishment of chromosome localization	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:BIRC5	involved_in	GO:0051301: cell division	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:BIRC5	involved_in	GO:0007094: mitotic spindle assembly checkpoint	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:BIRC5	involved_in	GO:0031536: positive regulation of exit from mitosis	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:BIRC5	involved_in	GO:0000281: mitotic cytokinesis	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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