File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: The kinetics of p53 activation Versus cyclin E accumulation underlies the relationship between the spindle-assembly checkpoint and the postmitotic checkpoint

TitleThe kinetics of p53 activation Versus cyclin E accumulation underlies the relationship between the spindle-assembly checkpoint and the postmitotic checkpoint
Authors
Issue Date2008
Citation
Journal of Biological Chemistry, 2008, v. 283, n. 23, p. 15716-15723 How to Cite?
AbstractAlthough cells can exit mitotic block aberrantly by mitotic slippage, they are prevented from becoming tetraploids by a p53-dependent postmitotic checkpoint. Intriguingly, disruption of the spindle-assembly checkpoint also compromises the postmitotic checkpoint. The precise mechanism of the interplay between these two pivotal checkpoints is not known. We found that after prolonged nocodazole exposure, the postmitotic checkpoint was facilitated by p53. We demonstrated that although disruption of the mitotic block by a MAD2-binding protein promoted slippage, it did not influence the activation of p53. Both p53 and its downstream target p21 CIP1/WAF1 were activated at the same rate irrespective of whether the spindle-assembly checkpoint was enforced or not. The accelerated S phase entry, as reflected by the premature accumulation of cyclin E relative to the activation of p21 CIP1/WAF1 , is the reason for the uncoupling of the postmitotic checkpoint. In support of this hypothesis, forced premature mitotic exit with a specific CDK1 inhibitor triggered DNA replication without affecting the kinetics of p53 activation. Finally, replication after checkpoint bypass was boosted by elevating the level of cyclin E. These observations indicate that disruption of the spindle-assembly checkpoint does not directly influence p53 activation, but the shortening of the mitotic arrest allows cyclin E-CDK2 to be activated before the accumulation of p21 CIP1/WAF1 . These data underscore the critical relationship between the spindle-assembly checkpoint and the postmitotic checkpoint in safeguarding chromosomal stability. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/268513
ISSN
2020 Impact Factor: 5.157
2020 SCImago Journal Rankings: 2.361
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYing, Wai Chan-
dc.contributor.authorKin, Fan On-
dc.contributor.authorWan, Mui Chan-
dc.contributor.authorWong, Winnie-
dc.contributor.authorHo, On Siu-
dc.contributor.authorPok, Man Hau-
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.citationJournal of Biological Chemistry, 2008, v. 283, n. 23, p. 15716-15723-
dc.identifier.issn0021-9258-
dc.identifier.urihttp://hdl.handle.net/10722/268513-
dc.description.abstractAlthough cells can exit mitotic block aberrantly by mitotic slippage, they are prevented from becoming tetraploids by a p53-dependent postmitotic checkpoint. Intriguingly, disruption of the spindle-assembly checkpoint also compromises the postmitotic checkpoint. The precise mechanism of the interplay between these two pivotal checkpoints is not known. We found that after prolonged nocodazole exposure, the postmitotic checkpoint was facilitated by p53. We demonstrated that although disruption of the mitotic block by a MAD2-binding protein promoted slippage, it did not influence the activation of p53. Both p53 and its downstream target p21 CIP1/WAF1 were activated at the same rate irrespective of whether the spindle-assembly checkpoint was enforced or not. The accelerated S phase entry, as reflected by the premature accumulation of cyclin E relative to the activation of p21 CIP1/WAF1 , is the reason for the uncoupling of the postmitotic checkpoint. In support of this hypothesis, forced premature mitotic exit with a specific CDK1 inhibitor triggered DNA replication without affecting the kinetics of p53 activation. Finally, replication after checkpoint bypass was boosted by elevating the level of cyclin E. These observations indicate that disruption of the spindle-assembly checkpoint does not directly influence p53 activation, but the shortening of the mitotic arrest allows cyclin E-CDK2 to be activated before the accumulation of p21 CIP1/WAF1 . These data underscore the critical relationship between the spindle-assembly checkpoint and the postmitotic checkpoint in safeguarding chromosomal stability. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.-
dc.languageeng-
dc.relation.ispartofJournal of Biological Chemistry-
dc.titleThe kinetics of p53 activation Versus cyclin E accumulation underlies the relationship between the spindle-assembly checkpoint and the postmitotic checkpoint-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1074/jbc.M800629200-
dc.identifier.pmid18400748-
dc.identifier.pmcidPMC3259627-
dc.identifier.scopuseid_2-s2.0-47049109949-
dc.identifier.volume283-
dc.identifier.issue23-
dc.identifier.spage15716-
dc.identifier.epage15723-
dc.identifier.eissn1083-351X-
dc.identifier.isiWOS:000256332500027-
dc.identifier.issnl0021-9258-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats