ArticleCell2020
Retracted: Allosteric Activators of Protein Phosphatase 2A Display Broad Antitumor Activity Mediated by Dephosphorylation of MYBL2.
Article in Cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 44 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.
The trial behind it
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
44 citing papers in PubMed.
- Nuclear-targeted GDOWN1 potently suppresses tumors by inducing premature transcription termination and exporting Pol Ⅱ CTD phosphatases to activate RB.Cell death and differentiation · 2026Article
- Multimodal fused deep learning for drug property prediction: Integrating chemical language and molecular graph.Computational and structural biotechnology journal · 2024Article
- gp78-regulated KAP1 phosphorylation induces radioresistance in breast cancer by facilitating PPP1CC/PPP2CA ubiquitination.iScience · 2024Article
- Large-scale genome-wide association studies reveal the genetic causal etiology between air pollutants and autoimmune diseases.Journal of translational medicine · 2024Article
- Article
- Altering phosphorylation in cancer through PP2A modifiers.Cancer cell international · 2024Review
- Genome-wide CRISPR/Cas9 screen identifies etoposide response modulators associated with clinical outcomes in pediatric AML.Blood advances · 2023Article
- Small-Molecule-Mediated Stabilization of PP2A Modulates the Homologous Recombination Pathway and Potentiates DNA Damage-Induced Cell Death.Molecular cancer therapeutics · 2023Article
- PP2Ac/STRN4 negatively regulates STING-type I IFN signaling in tumor-associated macrophages.The Journal of clinical investigation · 2023Article
- Simultaneous inhibition of endocytic recycling and lysosomal fusion sensitizes cells and tissues to oligonucleotide therapeutics.Nucleic acids research · 2023Article
- Transcription factor E2F8 is a therapeutic target in the basal-like subtype of breast cancer.Frontiers in oncology · 2023Article
- Chronic hypoxia leads to cognitive impairment by promoting HIF-2α-mediated ceramide catabolism and alpha-synuclein hyperphosphorylation.Cell death discovery · 2022Article
- Non-catalytic allostery in α-TAT1 by a phospho-switch drives dynamic microtubule acetylation.The Journal of cell biology · 2022Article
- MYC and therapy resistance in cancer: risks and opportunities.Molecular oncology · 2022Review
- Discovery of Novel Small-Molecule Scaffolds for the Inhibition and Activation of WIP1 Phosphatase from a RapidFire Mass Spectrometry High-Throughput Screen.ACS pharmacology & translational science · 2022Article
- Targets for Renal Carcinoma Growth Control Identified by Screening FOXD1 Cell Proliferation Pathways.Cancers · 2022Article
- TF-DUBTACs Stabilize Tumor Suppressor Transcription Factors.Journal of the American Chemical Society · 2022Article
- Chemogenetic profiling reveals PP2A-independent cytotoxicity of proposed PP2A activators iHAP1 and DT-061.The EMBO journal · 2022Article
- Sensitization of FOLFOX-resistant colorectal cancer cells via the modulation of a novel pathway involving protein phosphatase 2A.iScience · 2022Article
- Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy.Signal transduction and targeted therapy · 2022Review
Corrections and comments
- Retraction · 2022-08-04Doing the Right Thing · Error in Methods · Results Not Reproducible ·
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- Retracted
Authors and funding
12 authors.
Funding
Abstract
Protein phosphatase 2A (PP2A) enzymes can suppress tumors, but they are often inactivated in human cancers overexpressing inhibitory proteins. Here, we identify a class of small-molecule iHAPs (improved heterocyclic activators of PP2A) that kill leukemia cells by allosterically assembling a specific heterotrimeric PP2A holoenzyme consisting of PPP2R1A (scaffold), PPP2R5E (B56ε, regulatory), and PPP2CA (catalytic) subunits. One compound, iHAP1, activates this complex but does not inhibit dopamine receptor D2, a mediator of neurologic toxicity induced by perphenazine and related neuroleptics. The PP2A complex activated by iHAP1 dephosphorylates the MYBL2 transcription factor on Ser241, causing irreversible arrest of leukemia and other cancer cells in prometaphase. In contrast, SMAPs, a separate class of compounds, activate PP2A holoenzymes containing a different regulatory subunit, do not dephosphorylate MYBL2, and arrest tumor cells in G1 phase. Our findings demonstrate that small molecules can serve as allosteric switches to activate distinct PP2A complexes with unique substrates.
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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.