ArticleScience signaling2009
Tumor suppression by PTEN requires the activation of the PKR-eIF2alpha phosphorylation pathway.
Article in Science signaling, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 80 citations in OpenAlex.
- Loss of MiR-664 Expression Enhances Cutaneous Malignant Melanoma Proliferation by Upregulating PLP2.Medicine · 2015Trial
- Mitochondrial dysfunction activates ADAMTS-5 expression via mt-dsRNA-PKR-Spi-1 axis in osteoarthritic chondrocytes.iScience · 2026Article
- The Fanconi Anemia Pathway Inhibits mTOR Signaling and Prevents Accelerated Translation in Head and Neck Cancer Cells.Cancers · 2025Article
- Polynucleotide phosphorylase protects against renal tubular injury via blocking mt-dsRNA-PKR-eIF2α axis.Nature communications · 2023Article
- Interferon-gamma modulates articular chondrocyte and osteoblast metabolism through protein kinase R-independent and dependent mechanisms.Biochemistry and biophysics reports · 2022Article
- Direct and indirect effects of IFN-α2b in malignancy treatment: not only an archer but also an arrow.Biomarker research · 2022Review
- The regulation of protein translation and its implications for cancer.Signal transduction and targeted therapy · 2021Review
- Redox Regulation of PTEN by Peroxiredoxins.Antioxidants (Basel, Switzerland) · 2021Review
- Targeted Deletion of PTEN in Kisspeptin Cells Results in Brain Region- and Sex-Specific Effects on Kisspeptin Expression and Gonadotropin Release.International journal of molecular sciences · 2020Article
- Salubrinal in Combination With 4E1RCat Synergistically Impairs Melanoma Development by Disrupting the Protein Synthetic Machinery.Frontiers in oncology · 2020Article
- An integrated stress response via PKR suppresses HER2+ cancers and improves trastuzumab therapy.Nature communications · 2019Article
- Starvation and Pseudo-Starvation as Drivers of Cancer Metastasis through Translation Reprogramming.Cell metabolism · 2019Review
- EZH2 Methyltransferase Activity Controls Pten Expression and mTOR Signaling during Fear Memory Reconsolidation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Integrating oncolytic viruses in combination cancer immunotherapy.Nature reviews. Immunology · 2018Review
- A gene signature associated with PTEN activation defines good prognosis intermediate risk prostate cancer cases.The journal of pathology. Clinical research · 2018Article
- Roles of protein kinase R in cancer: Potential as a therapeutic target.Cancer science · 2018Review
- The eIF2-alpha kinase HRI: a potential target beyond the red blood cell.Expert opinion on therapeutic targets · 2017Review
- Citrate Suppresses Tumor Growth in Multiple Models through Inhibition of Glycolysis, the Tricarboxylic Acid Cycle and the IGF-1R Pathway.Scientific reports · 2017Article
- Smad7 knockdown activates protein kinase RNA-associated eIF2α pathway leading to colon cancer cell death.Cell death & disease · 2017Article
- Correction of PTEN mutations in glioblastoma cell lines via AAV-mediated gene editing.PloS one · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Inhibition of protein synthesis by phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2) at Ser(51) occurs as a result of the activation of a family of kinases in response to various forms of stress. Although some consequences of eIF2alpha phosphorylation are cytoprotective, phosphorylation of eIF2alpha by RNA-dependent protein kinase (PKR) is largely proapoptotic and tumor suppressing. Phosphatase and tensin homolog deleted from chromosome 10 (PTEN) is a tumor suppressor protein that is mutated or deleted in various human cancers, with functions that are mediated through phosphatase-dependent and -independent pathways. Here, we demonstrate that the eIF2alpha phosphorylation pathway is downstream of PTEN. Inactivation of PTEN in human melanoma cells reduced eIF2alpha phosphorylation, whereas reconstitution of PTEN-null human glioblastoma or prostate cancer cells with either wild-type PTEN or phosphatase-defective mutants of PTEN induced PKR activity and eIF2alpha phosphorylation. The antiproliferative and proapoptotic effects of PTEN were compromised in mouse embryonic fibroblasts that lacked PKR or contained a phosphorylation-defective variant of eIF2alpha. Induction of the pathway leading to phosphorylation of eIF2alpha required an intact PDZ-binding motif in PTEN. These findings establish a link between tumor suppression by PTEN and inhibition of protein synthesis that is independent of PTEN's effects on phosphoinositide 3'-kinase signaling.
Indexed as
Identifiers
What OpenQuestion holds
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.