14-3-3σ is required to prevent mitotic catastrophe after DNA damage View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1999-10

AUTHORS

Timothy A. Chan, Heiko Hermeking, Christoph Lengauer, Kenneth W. Kinzler, Bert Vogelstein

ABSTRACT

14-3-3Sigma is a member of a family of proteins that regulate cellular activity by binding and sequestering phosphorylated proteins. It has been suggested that 14-3-3sigma promotes pre-mitotic cell-cycle arrest following DNA damage, and that its expression can be controlled by the p53 tumour suppressor gene. Here we describe an improved approach to the generation of human somatic-cell knockouts, which we have used to generate human colorectal cancer cells in which both 14-3-3sigma alleles are inactivated. After DNA damage, these cells initially arrested in the G2 phase of the cell cycle, but, unlike cells containing 14-3-3sigma, the 14-3-3sigma-/- cells were unable to maintain cell-cycle arrest. The 14-3-3sigma-/- cells died ('mitotic catastrophe') as they entered mitosis. This process was associated with a failure of the 14-3-3sigma-deficient cells to sequester the proteins (cyclin B1 and cdc2) that initiate mitosis and prevent them from entering the nucleus. These results may indicate a mechanism for maintaining the G2 checkpoint and preventing mitotic death. More... »

PAGES

616

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/44188

DOI

http://dx.doi.org/10.1038/44188

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1044218520

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/10524633


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