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Article: CDK1 inhibitors antagonize the immediate apoptosis triggered by spindle disruption but promote apoptosis following the subsequent rereplication and abnormal mitosis

TitleCDK1 inhibitors antagonize the immediate apoptosis triggered by spindle disruption but promote apoptosis following the subsequent rereplication and abnormal mitosis
Authors
KeywordsNocodazole
Spindle-assembly checkpoint
Cell cycle
Checkpoint
Cyclin
Mitosis
Issue Date2008
Citation
Cell Cycle, 2008, v. 7, n. 10, p. 1449-1461 How to Cite?
AbstractSpindle-disrupting agents and CDK inhibitors are important cancer therapeutic agents. Spindle toxins activate the spindle-assembly checkpoint and lead to sustained activation of CDK1. Different published results indicate that CDK1 activity is either important or dispensable for the cytotoxicity associated with spindle disruption. Using live cell imaging and various approaches that uncoupled mitotic events, we show that apoptosis was induced by both prolonged nocodazole treatment as well as by inhibition of CDK1 activity after a transient nocodazole block. However, distinct mechanisms are involved in the two types of cell death. The massive apoptosis triggered by nocodazole treatment requires the continuous activation of cyclin B1-CDK1 and is antagonized by premature mitotic slippage. By contrast, apoptosis induced by nocodazole followed by CDK inhibitors occurred after rereplication and multipolar mitosis of the subsequent cell cycle. The presence of dual mechanisms of cytotoxicity mediated by spindle disruption and CDK inhibition may reconcile the various apparent inconsistent published results. These data underscore the essential role of cyclin B1-CDK1 as the basis of apoptosis during mitotic arrest, and the role of mitotic slippage and abnormal mitosis for apoptosis at later stages. ©2008 Landes Bioscience.
Persistent Identifierhttp://hdl.handle.net/10722/268511
ISSN
2023 Impact Factor: 3.4
2023 SCImago Journal Rankings: 0.947
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChan, Ying Wai-
dc.contributor.authorMa, Hoi Tang-
dc.contributor.authorWong, Winnie-
dc.contributor.authorHo, Chui Chui-
dc.contributor.authorOn, Kin Fan-
dc.contributor.authorPoon, Randy Y.C.-
dc.date.accessioned2019-03-25T07:59:53Z-
dc.date.available2019-03-25T07:59:53Z-
dc.date.issued2008-
dc.identifier.citationCell Cycle, 2008, v. 7, n. 10, p. 1449-1461-
dc.identifier.issn1538-4101-
dc.identifier.urihttp://hdl.handle.net/10722/268511-
dc.description.abstractSpindle-disrupting agents and CDK inhibitors are important cancer therapeutic agents. Spindle toxins activate the spindle-assembly checkpoint and lead to sustained activation of CDK1. Different published results indicate that CDK1 activity is either important or dispensable for the cytotoxicity associated with spindle disruption. Using live cell imaging and various approaches that uncoupled mitotic events, we show that apoptosis was induced by both prolonged nocodazole treatment as well as by inhibition of CDK1 activity after a transient nocodazole block. However, distinct mechanisms are involved in the two types of cell death. The massive apoptosis triggered by nocodazole treatment requires the continuous activation of cyclin B1-CDK1 and is antagonized by premature mitotic slippage. By contrast, apoptosis induced by nocodazole followed by CDK inhibitors occurred after rereplication and multipolar mitosis of the subsequent cell cycle. The presence of dual mechanisms of cytotoxicity mediated by spindle disruption and CDK inhibition may reconcile the various apparent inconsistent published results. These data underscore the essential role of cyclin B1-CDK1 as the basis of apoptosis during mitotic arrest, and the role of mitotic slippage and abnormal mitosis for apoptosis at later stages. ©2008 Landes Bioscience.-
dc.languageeng-
dc.relation.ispartofCell Cycle-
dc.subjectNocodazole-
dc.subjectSpindle-assembly checkpoint-
dc.subjectCell cycle-
dc.subjectCheckpoint-
dc.subjectCyclin-
dc.subjectMitosis-
dc.titleCDK1 inhibitors antagonize the immediate apoptosis triggered by spindle disruption but promote apoptosis following the subsequent rereplication and abnormal mitosis-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.4161/cc.7.10.5880-
dc.identifier.pmid18418077-
dc.identifier.scopuseid_2-s2.0-45749123913-
dc.identifier.volume7-
dc.identifier.issue10-
dc.identifier.spage1449-
dc.identifier.epage1461-
dc.identifier.eissn1551-4005-
dc.identifier.isiWOS:000256438500021-
dc.identifier.issnl1551-4005-

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