Cited by 89514-3-3 protein interactionsDNA Repair MechanismsCancer-related Molecular Pathways

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

Chan, Timothy A., Hermeking, Heiko, Lengauer, Christoph, Kinzler, Kenneth W., Vogelstein, Bert·1999·Nature

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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.

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Authors: Chan, T. A., Hermeking, H., Lengauer, C., Kinzler, K. W., & Vogelstein, B.
Affiliations: Johns Hopkins University (US)
Howard Hughes Medical Institute (US)
Corresponding author: Vogelstein, Bert
ORCID: Chan, Timothy A.
Hermeking, Heiko
Kinzler, Kenneth W.
Vogelstein, Bert
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1999-10-07
Volume: 401
Issue: 6753
Pages: 616-620
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/44188
OpenAlex: W2130603065
Cited by: 895
References: 20
Citations by year: 2026: 4 · 2025: 5 · 2024: 4 · 2023: 15 · 2022: 10 · 2021: 16 · 2020: 21 · 2019: 8 · 2018: 8 · 2017: 16 · 2016: 10 · 2015: 19 · 2014: 31 · 2013: 30 · 2012: 30
FWCI: 21.59
Type: journal article
Language: en
Update notices: correction (2023-08-22)
Open access: closed
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: Johns Hopkins University
National Institutes of Health
Natural Sciences and Engineering Research Council of Canada
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › 14-3-3 protein interactions
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords: 14-3-3 sigma, mitotic catastrophe, DNA damage, G2 checkpoint, cell cycle arrest, cyclin B1, cdc2, protein sequestration, p53, colorectal cancer cells, mitosis initiation
MeSH terms: Cloning, Molecular, DNA Damage, Humans, Mitosis, Proteins, Tumor Cells, Cultured, Tyrosine 3-Monooxygenase, G2 Phase, Cell Cycle Proteins, Cyclin B, cdc25 Phosphatases, 14-3-3 Proteins, Cyclin B1

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

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