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Identification of specific PP2A complexes involved in human cell transformation
Open accessAbstract
The SV40 small t antigen (ST) interacts with the serine-threonine protein phosphatase 2A (PP2A). To investigate the role of this interaction in transformation, we suppressed the expression of the PP2A B56gamma subunit in human embryonic kidney (HEK) epithelial cells expressing SV40 large T antigen, hTERT, and H-RAS. Suppression of PP2A B56gamma expression inhibited PP2A-specific phosphatase activity similar to that achieved by ST and conferred the ability to grow in an anchorage-independent fashion and to form tumors. Overexpression of PP2A B56gamma3 in tumorigenic HEK cells expressing ST or human lung cancer cell lines partially reversed the tumorigenicity of these cells. These observations identify specific PP2A complexes involved in human cell transformation.
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PP2A trimers with B56 subunits are predominantly human tumour suppressors.
“Among the PP2A complexes, PP2A trimers with B56 subunits are predominantly human tumour suppressors4–7.”
From Structural mechanism for inhibition of PP2A-B56α and oncogenicity by CIP2A (2023) · cites this paper as [7]
CIP2A K21A targeted clones were almost completely incompetent to grow as spheres on soft agar.
“However, fully consistent with the requirement of PP2A-B56 inhibition for anchorage-independent growth6,7, CIP2A K21A targeted clones were almost completely incompetent to grow as spheres on soft agar (Fig. 3F, G).”
From Structural mechanism for inhibition of PP2A-B56α and oncogenicity by CIP2A (2023) · cites this paper as [7]
PP2A-B56α is a human tumour suppressor.
“The protein phosphatase 2A (PP2A) heterotrimer PP2A-B56α is a human tumour suppressor.”
From Structural mechanism for inhibition of PP2A-B56α and oncogenicity by CIP2A (2023) · cites this paper as [7]
Ectopic B56γ expression in lung, breast and prostate cancer cell lines reduces proliferation and colony formation in soft agar.
“Consistently, ectopic expression of B56γ in lung, breast and prostate cancer cell lines reduced cell proliferation and colony formation in soft agar, suggesting a potential tumor suppressor role of B56γ in multiple cell types (Chen et al., 2004).”
From PP2A holoenzymes, substrate specificity driving cellular functions and deregulation in cancer (2019) · cites this paper as Chen et al., 2004
The role of B′ subunits as tumor suppressors is corroborated by the notion that B′ subunit knockdown causes polyploidy.
“This notion corroborates with the previous notion on the role of B′ subunits as tumor suppressors [45–49].”
From PP2A-B′ holoenzyme substrate recognition, regulation and role in cytokinesis (2017) · cites this paper as [49]
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Metadata
- Authors
- Chen, W., Possemato, R., Campbell, K. T., Plattner, C. A., Pallas, D. C., & Hahn, W. C.
- Affiliations
- Brigham and Women's Hospital (US)
- Emory University (US)
- Corresponding author
- Hahn, William C
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2004-02
- Volume
- 5
- Issue
- 2
- Pages
- 127-136
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W1971212979
- Cited by
- 325
- References
- 56
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 2 · 2023: 14 · 2022: 10 · 2021: 12 · 2020: 14 · 2019: 16 · 2018: 13 · 2017: 9 · 2016: 8 · 2015: 13 · 2014: 15 · 2013: 14 · 2012: 19
- FWCI
- 9.95
- Type
- journal article
- Language
- en
- Update notices
- erratum (2024-06-10)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R01 CA57327, P01 CA 50661, K01CA94223, K01CA094223, P01CA050661, R01CA057327)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- protein phosphatase 2A, small T antigen, SV40 large T antigen, cell transformation, anchorage-independent growth, tumorigenicity, H-Ras, hTERT, lung cancer
- MeSH terms
- Animals, Antigens, Viral, Tumor, Cell Transformation, Neoplastic, Cells, Cultured, Cloning, Molecular, DNA-Binding Proteins, Enzyme Activation, Epithelial Cells, Humans, Phosphoprotein Phosphatases, Phosphorylation, Protein Binding, Genes, ras, Signal Transduction, Telomerase, Protein Subunits, Protein Phosphatase 2
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