ArticleNeoplasia (New York, N.Y.)2012
Circumventing cellular control of PP2A by methylation promotes transformation in an Akt-dependent manner.
Article in Neoplasia (New York, N.Y.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 59 citations in OpenAlex.
- HIF-1-mediated PPME1 expression promotes breast cancer progression via AKT activation and β-catenin recruitment.The Journal of clinical investigation · 2026Article
- Pan-cancer analysis of ARNT2 and its oncogenic role in cervical cancer.Journal of gynecologic oncology · 2025Article
- Alzheimer's Disease and Cancer: Common Targets.Mini reviews in medicinal chemistry · 2024Review
- Loss of LCMT1 and biased protein phosphatase 2A heterotrimerization drive prostate cancer progression and therapy resistance.Nature communications · 2023Article
- LCMT1 indicates poor prognosis and is essential for cell proliferation in hepatocellular carcinoma.Translational oncology · 2023Article
- Biased holoenzyme assembly of protein phosphatase 2A (PP2A): From cancer to small molecules.The Journal of biological chemistry · 2022Review
- A functional interaction between liprin-α1 and B56γ regulatory subunit of protein phosphatase 2A supports tumor cell motility.Communications biology · 2022Article
- Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy.Signal transduction and targeted therapy · 2022Review
- Targeting Ribonucleotide Reductase Induces Synthetic Lethality in PP2A-Deficient Uterine Serous Carcinoma.Cancer research · 2022Article
- Potential of phenothiazines to synergistically block calmodulin and reactivate PP2A in cancer cells.PloS one · 2022Article
- Ribosomal Protein S6: A Potential Therapeutic Target against Cancer?International journal of molecular sciences · 2021Review
- Protein phosphatase 2A inactivation induces microsatellite instability, neoantigen production and immune response.Nature communications · 2021Article
- Regulation of PP2A, PP4, and PP6 holoenzyme assembly by carboxyl-terminal methylation.Scientific reports · 2021Article
- Effects of carboxyl-terminal methylation on holoenzyme function of the PP2A subfamily.Biochemical Society transactions · 2020Review
- Article
- Phosphoproteome and drug-response effects mediated by the three protein phosphatase 2A inhibitor proteins CIP2A, SET, and PME-1.The Journal of biological chemistry · 2020Article
- Protein Phosphatase 2A as a Drug Target in the Treatment of Cancer and Alzheimer's Disease.Current medical science · 2020Review
- RABL6A inhibits tumor-suppressive PP2A/AKT signaling to drive pancreatic neuroendocrine tumor growth.The Journal of clinical investigation · 2019Article
- NNMT depletion contributes to liver cancer cell survival by enhancing autophagy under nutrient starvation.Oncogenesis · 2018Article
- Global loss of leucine carboxyl methyltransferase-1 causes severe defects in fetal liver hematopoiesis.The Journal of biological chemistry · 2018Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Heterotrimeric protein phosphatase 2A (PP2A) consists of catalytic C (PP2Ac), structural A, and regulatory B-type subunits, and its dysfunction has been linked to cancer. Reversible methylation of PP2Ac by leucine carboxyl methyltransferase 1 (LCMT-1) and protein phosphatase methylesterase 1 (PME-1) differentially regulates B-type subunit binding and thus PP2A function. Polyomavirus middle (PyMT) and small (PyST) tumor antigens and SV40 small tumor antigen (SVST) are oncoproteins that block PP2A function by replacing certain B-type subunits, resulting in cellular transformation. Whereas the B-type subunits replaced by these oncoproteins seem to exhibit a binding preference for methylated PP2Ac, PyMT does not. We hypothesize that circumventing the normal cellular control of PP2A by PP2Ac methylation is a general strategy for ST- and MT-mediated transformation. Two predictions of this hypothesis are (1) that PyST and SVST also bind PP2A in a methylation-insensitive manner and (2) that down-regulation of PP2Ac methylation will activate progrowth and prosurvival signaling and promote transformation. We found that SVST and PyST, like PyMT, indeed form PP2A heterotrimers independently of PP2Ac methylation. In addition, reducing PP2Ac methylation through LCMT-1 knockdown or PME-1 overexpression enhanced transformation by activating the Akt and p70/p85 S6 kinase (S6K) pathways, pathways also activated by MT and ST oncoproteins. These results support the hypothesis that MT and ST oncoproteins circumvent cellular control of PP2A by methylation to promote transformation. They also implicate LCMT-1 as a negative regulator of Akt and p70/p85 S6K. Therefore, disruption of PP2Ac methylation may contribute to cancer, and modulation of this methylation may serve as an anticancer target.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.