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Article: Depletion of p31comet protein promotes sensitivity to antimitotic drugs

TitleDepletion of p31<sup>comet</sup> protein promotes sensitivity to antimitotic drugs
Authors
Issue Date2012
Citation
Journal of Biological Chemistry, 2012, v. 287, n. 25, p. 21561-21569 How to Cite?
AbstractAntimitotic spindle poisons are among the most important chemotherapeutic agents available. However, precocious mitotic exit by mitotic slippage limits the cytotoxicity of spindle poisons. The MAD2-binding protein p31 comet is implicated in silencing the spindle assembly checkpoint after all kinetochores are attached to spindles. In this study, we report that the levels of p31 comet andMAD2in different cell lines are closely linked with susceptibility to mitotic slippage. Down-regulation of p31 comet increased the sensitivity of multiple cancer cell lines to spindle poisons, including nocodazole, vincristine, and Taxol. In the absence of p31 comet, lower concentrations of spindle poisons were required to induce mitotic block. The delay in checkpoint silencing was induced by an accumulation of mitotic checkpoint complexes. The increase in the duration of mitotic block after p31 comet depletion resulted in a dramatic increase in mitotic cell death upon challenge with spindle poisons. Significantly, cells that are normally prone to mitotic slippage and resistant to spindle disruption-mediated mitotic death were also sensitized after p31 comet depletion. These results highlight the importance of p31 comet in checkpoint silencing and its potential as a target for antimitotic therapies. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/307356
ISSN
2020 Impact Factor: 5.157
2023 SCImago Journal Rankings: 1.766
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorMa, Hoi Tang-
dc.contributor.authorChan, Yan Yan-
dc.contributor.authorChen, Xiao-
dc.contributor.authorOn, Kin Fan-
dc.contributor.authorPoon, Randy Y.C.-
dc.date.accessioned2021-11-03T06:22:26Z-
dc.date.available2021-11-03T06:22:26Z-
dc.date.issued2012-
dc.identifier.citationJournal of Biological Chemistry, 2012, v. 287, n. 25, p. 21561-21569-
dc.identifier.issn0021-9258-
dc.identifier.urihttp://hdl.handle.net/10722/307356-
dc.description.abstractAntimitotic spindle poisons are among the most important chemotherapeutic agents available. However, precocious mitotic exit by mitotic slippage limits the cytotoxicity of spindle poisons. The MAD2-binding protein p31 comet is implicated in silencing the spindle assembly checkpoint after all kinetochores are attached to spindles. In this study, we report that the levels of p31 comet andMAD2in different cell lines are closely linked with susceptibility to mitotic slippage. Down-regulation of p31 comet increased the sensitivity of multiple cancer cell lines to spindle poisons, including nocodazole, vincristine, and Taxol. In the absence of p31 comet, lower concentrations of spindle poisons were required to induce mitotic block. The delay in checkpoint silencing was induced by an accumulation of mitotic checkpoint complexes. The increase in the duration of mitotic block after p31 comet depletion resulted in a dramatic increase in mitotic cell death upon challenge with spindle poisons. Significantly, cells that are normally prone to mitotic slippage and resistant to spindle disruption-mediated mitotic death were also sensitized after p31 comet depletion. These results highlight the importance of p31 comet in checkpoint silencing and its potential as a target for antimitotic therapies. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.-
dc.languageeng-
dc.relation.ispartofJournal of Biological Chemistry-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleDepletion of p31<sup>comet</sup> protein promotes sensitivity to antimitotic drugs-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1074/jbc.M112.364356-
dc.identifier.pmid22544748-
dc.identifier.pmcidPMC3375577-
dc.identifier.scopuseid_2-s2.0-84862302002-
dc.identifier.volume287-
dc.identifier.issue25-
dc.identifier.spage21561-
dc.identifier.epage21569-
dc.identifier.eissn1083-351X-
dc.identifier.isiWOS:000306416800073-
dc.identifier.f1000716298024-

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