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14-3-3σ is required to prevent mitotic catastrophe after DNA damage
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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“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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Dellambra, E., Golisano, O., Bondanza, S., Siviero, E., Lacal, P. M., Molinari, M., D’Atri, S., & Luca, M. D. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.149.5.1117 · Cited by 224
Cellular Responses to DNA Damage: One Signal, Multiple Choices
Su, T. T. (2006) · Annual Review of Genetics · doi:10.1146/annurev.genet.40.110405.090428 · Cited by 235
Physical Interaction with Human Tumor-derived p53 Mutants Inhibits p63 Activities
Strano, S., Fontemaggi, G., Costanzo, A., Rizzo, M. G., Monti, O., Baccarini, A., Sal, G. D., Levrero, M., Sacchi, A., Oren, M., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201405200 · Cited by 225
14-3-3 Proteins: A Number of Functions for a Numbered Protein
Bridges, D., & Moorhead, G. B. G. (2005) · Science s STKE · doi:10.1126/stke.2962005re10 · Cited by 230
Metadata
- 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
- Update notices
- correction (2023-08-22)
- Open access
- closed
- Licence
- 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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