Nuclear PTEN controls DNA repair and sensitivity to genotoxic stress
Open accessAbstract
PTEN Variations: The product of the tumor suppressor gene phosphate and tensin homolog on chromosome ten ( PTEN) is a lipid and protein phosphatase that regulates important cellular processes, including growth, survival, and metabolism (see the Perspective by Leslie and Brunton ). Though PTEN is best known for effects on the phosphatidylnositol 3-kinase (PI3K) signaling pathway, the PTEN protein is also found in the nucleus. Bassi et al. (p. 395 ) found that PTEN's presence in the nucleus was regulated in response to covalent modification of the protein by SUMOylation and phosphorylation. Cells lacking nuclear PTEN showed increased sensitivity to DNA damage and underwent cell death if the PI3K pathway was also inhibited. Hopkins et al. (p. 399 , published online 6 June) discovered an alternative translation start site in human PTEN messenger RNA that allowed expression of a protein, PTEN-Long, with about 170 extra amino acids. The unusual enzyme was released from cells and then taken up into other cells. In a mouse tumor model, uptake of the enzyme inhibited the PI3K pathway and inhibited tumor growth.
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Nuclear PTEN is involved in DNA repair, and cells without nuclear PTEN are more sensitive to DNA damage.
“Bassiet et al. [91] demonstrated that nuclear PTEN is involved in DNA repair, and cells without nuclear PTEN are more sensitive to DNA damage.”
From Repair of Oxidative DNA Damage, Cell-Cycle Regulation and Neuronal Death May Influence the Clinical Manifestation of Alzheimer’s Disease (2014) · cites this paper as [91]
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- Authors
- Bassi, C., Ho, J., Srikumar, T., Dowling, R. J. O., Gorrini, C., Miller, S. J., Mak, T. W., Neel, B. G., Raught, B., & Stambolic, V.
- Affiliations
- University of Toronto (CA)
- University Health Network (CA)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Stambolic, V.
- ORCID
- Venue
- Science
- Published
- 2013-07-26
- Volume
- 341
- Issue
- 6144
- Pages
- 395-399
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC5087104
- OpenAlex
- W2022159597
- Cited by
- 403
- References
- 25
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 26 · 2023: 24 · 2022: 26 · 2021: 26 · 2020: 45 · 2019: 39 · 2018: 24 · 2017: 36 · 2016: 32 · 2015: 43 · 2014: 43 · 2013: 12
- FWCI
- 19.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- TSpace (University of Toronto) (submittedVersion)
- Funders
- Canadian Institutes of Health Research
- National Cancer Institute (R37CA49152, R37CA049152, R01CA049152)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- PTEN, DNA repair, genotoxic stress, SUMOylation, protein phosphorylation, PI3K signaling, alternative translation start sites, tumor suppressor, phosphatase, tumor growth inhibition
- MeSH terms
- Phosphoinositide-3 Kinase Inhibitors, Aminopyridines, Animals, Antineoplastic Agents, Cell Line, Cell Nucleus, Cisplatin, DNA Damage, DNA Repair, DNA-Binding Proteins, Doxorubicin, Enzyme Inhibitors, Female, Humans, Morpholines, Neoplasm Transplantation, Phosphorylation, Transplantation, Heterologous, Mice, SCID, Mice, Inbred NOD, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Active Transport, Cell Nucleus, Tumor Suppressor Proteins, Cell Line, Tumor, PTEN Phosphohydrolase, Mice, DNA Breaks, Double-Stranded, Sumoylation, Ataxia Telangiectasia Mutated Proteins
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