ArticleLeukemia2019
Mitochondrial apoptosis is induced by Alkoxy phenyl-1-propanone derivatives through PP2A-mediated dephosphorylation of Bad and Foxo3A in CLL.
Article in Leukemia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
18 citing papers in PubMed, 34 citations in OpenAlex.
- Protein serine/threonine phosphatases in tumor microenvironment: a vital player and a promising therapeutic target.Theranostics · 2025Review
- Innovative Combinations, Cellular Therapies and Bispecific Antibodies for Chronic Lymphocytic Leukemia: A Narrative Review.Cancers · 2024Review
- Protein kinase CK2α is overexpressed in classical hodgkin lymphoma, regulates key signaling pathways, PD-L1 and may represent a new target for therapy.Frontiers in immunology · 2024Article
- PP2A modulation overcomes multidrug resistance in chronic lymphocytic leukemia via mPTP-dependent apoptosis.The Journal of clinical investigation · 2023Article
- Targeting protein phosphatases in cancer immunotherapy and autoimmune disorders.Nature reviews. Drug discovery · 2023Review
- Inhibition of PP2A by LB100 sensitizes bladder cancer cells to chemotherapy by inducing p21 degradation.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- Protein Phosphorylation and Redox Status: An as Yet Elusive Dyad in Chronic Lymphocytic Leukemia.Cancers · 2022Review
- GSK3β is a critical, druggable component of the network regulating the active NOTCH1 protein and cell viability in CLL.Cell death & disease · 2022Article
- PP2A promotes apoptosis and facilitates docetaxel sensitivity via the PP2A/p-eIF4B/XIAP signaling pathway in prostate cancer.Oncology letters · 2022Article
- Effect of CMB Carrying PTX and CRISPR/Cas9 on Endometrial Cancer Naked Mouse Model.Journal of healthcare engineering · 2022Article
- Drug Design: Where We Are and Future Prospects.Molecules (Basel, Switzerland) · 2021Review
- PP2A and tumor radiotherapy.Hereditas · 2020Review
- Oxidation Impacts the Intracellular Signaling Machinery in Hematological Disorders.Antioxidants (Basel, Switzerland) · 2020Review
- FKBP5 Exacerbates Impairments in Cerebral Ischemic Stroke by Inducing AutophagyFrontiers in cellular neuroscience · 2020Article
- Lights and Shade of Next-Generation Pi3k Inhibitors in Chronic Lymphocytic Leukemia.OncoTargets and therapy · 2020Review
- Article
- PP2A holoenzymes, substrate specificity driving cellular functions and deregulation in cancer.Advances in cancer research · 2019Review
- Development and Clinical Applications of PI3K/AKT/mTOR Pathway Inhibitors as a Therapeutic Option for Leukemias.Cancer diagnosis & prognosisReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein phosphatase 2 A (PP2A) is a tumour suppressor whose strong inhibition underlies the phosphorylation-dependent, anti-apoptotic mechanisms in Chronic Lymphocytic Leukemia (CLL). Inactivation of PP2A is due to the cooperative action of the phosphorylation of Y307 of its catalytic subunit by the aberrant cytosolic pool of the Src Family Kinase Lyn and the interaction with its protein inhibitor SET, which is overexpressed in CLL. In this study, we developed a library of compounds, the most potent being the one named CC11, which restores PP2A activity by disrupting the PP2A/SET complex, thereby triggering the mitochondrial pathway of apoptosis. This process involves the recruitment of the pro-apoptotic BH3-only proteins Bad and Bim to mitochondria, the former upon direct dephosphorylation and the latter being newly expressed upon dephosphorylation and activation of its transcription factor FoxO3a. These findings highlight that PP2A antagonizes the prosurvival pathways controlled by Akt, which phosphorylates and thereby suppresses a variety of pro-apoptotic factors and tumour suppressors including Bad and FoxO3a. Furthermore, the PP2A-mediated pro-apoptotic effect of CC11 is synergistically potentiated by the abrogation of Lyn's activity. Our results show that CC11 represents a promising lead compound for a new therapeutic rationale aimed at abrogating the aberrant oncogenic signals in CLL.
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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.