ArticleBlood cancer journal2013
PKR negatively regulates leukemia progression in association with PP2A activation, Bcl-2 inhibition and increased apoptosis.
Article in Blood cancer journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 27 citations in OpenAlex.
- OR2T6 modulates autophagy through the PPP3CA-mediated pathways to suppress gastric cancer.Cell death and differentiation · 2026Article
- The roles of phosphorylation of signaling proteins in the prognosis of acute myeloid leukemia.Pathology oncology research : POR · 2024Article
- A Renaissance for Oncolytic Adenoviruses?Viruses · 2023Review
- Long non-coding RNA DARS-AS1 promotes tumor progression by directly suppressing PACT-mediated cellular stress.Communications biology · 2022Article
- UBR5 promotes tumor immune evasion through enhancing IFN-γ-inducedTheranostics · 2022Article
- Salidroside induces cell apoptosis and inhibits the invasiveness of HT29 colorectal cells by regulating protein kinase R, NF-κB and STAT3.Cancer biomarkers : section A of Disease markers · 2021Article
- Article
- Mechanism mediated by a noncoding RNA, nc886, in the cytotoxicity of a DNA-reactive compound.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Quantitative Proteomic Analysis Reveals That Arctigenin Alleviates Concanavalin A-Induced Hepatitis Through Suppressing Immune System and Regulating Autophagy.Frontiers in immunology · 2018Article
- Polycystin-1 inhibits eIF2α phosphorylation and cell apoptosis through a PKR-eIF2α pathway.Scientific reports · 2017Article
- Smad7 knockdown activates protein kinase RNA-associated eIF2α pathway leading to colon cancer cell death.Cell death & disease · 2017Article
- Hypoxia promotes chemoresistance in acute lymphoblastic leukemia cell lines by modulating death signaling pathways.BMC cancer · 2016Article
- The antineoplastic properties of FTY720: evidence for the repurposing of fingolimod.Journal of cellular and molecular medicine · 2015Review
- Article
- Protein Phosphatase 2A Mediates Oxidative Stress Induced Apoptosis in Osteoblasts.Mediators of inflammation · 2015Article
- From the Biology of PP2A to the PADs for Therapy of Hematologic Malignancies.Frontiers in oncology · 2015Review
- Alterations of Mitochondria and Related Metabolic Pathways in Leukemia: A Narrative Review.Saudi journal of medicine & medical sciencesReview
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Reduced expression and activity of the proapoptotic, double-stranded RNA-dependent protein kinase, PKR (protein kinase R) is observed in breast, lung and various leukemias, suggesting that loss of PKR potentiates transformation. Now we report that decreased PKR activity inhibits chemotherapy-induced apoptosis of leukemia cells both in vitro and in vivo. Inhibition of PKR expression or activity reduces protein phosphatase 2A (PP2A) activity, a B-cell lymphoma 2 (Bcl-2) phosphatase, resulting in enhanced Bcl-2 phosphorylation. Thus, inhibition of PKR activity leads to hyperphosphorylation of Bcl-2, stabilization of Bcl-2/Bax interaction and decreased Bax insertion into the outer mitochondrial membrane. Treatment with the PP2A activator, FTY720, restores Bcl-2 dephosphorylation and apoptosis in cells with reduced PKR expression following stress. Significantly, xenografts of REH leukemic cells with reduced PKR display significantly increased tumor volume, increased resistance to doxorubicin treatment and shorter survival. Importantly, FTY720 treatment restores sensitivity to chemotherapy and prolongs overall survival of these mice. Collectively, these findings suggest that PP2A activation is a downstream target of PKR and the PKR/PP2A signaling axis is required for rapid and potent stress-induced apoptosis. Importantly, loss of PKR promotes leukemia progression and may serve as a biomarker for predicting chemosensitivity.
Identifiers
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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.