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

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

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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Crossref · 10.1038/44188

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  • SFN (14-3-3 sigma) encodes a protein that removes cell cycle proteins from the nucleus and is required for G2/M arrest.

    “SFN (14-3-3 sigma) encodes for a protein that removes cell cycle proteins from the nucleus and is also required for the G2/M arrest.51, 157”

    From Census and evaluation of p53 target genes (2017) · cites this paper as [157]

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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
Venue
Nature
Published
1999-10-07
Volume
401
Issue
6753
Pages
616-620
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
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
Open access
closed
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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