ArticleProceedings of the National Academy of Sciences of the United States of America2009
PKR, a p53 target gene, plays a crucial role in the tumor-suppressor function of p53.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 126 citations in OpenAlex.
- Mammalian mitohormesis: from mitochondrial stressors to organismal benefits.The EMBO journal · 2025Review
- PKR associates with 4.1R to promote anchorage-independent growth of hepatocellular carcinoma and lead to poor prognosis.Scientific reports · 2024Article
- Triggering Degradation of Host Cellular Proteins for Robust Propagation of Influenza Viruses.International journal of molecular sciences · 2024Review
- C16, a PKR inhibitor, suppresses cell proliferation by regulating the cell cycle via p21 in colorectal cancer.Scientific reports · 2024Article
- Integrated Stress Response (ISR) Pathway: Unraveling Its Role in Cellular Senescence.International journal of molecular sciences · 2023Review
- A co-formulation of interferons alpha2b and gamma distinctively targets cell cycle in the glioblastoma-derived cell line U-87MG.BMC cancer · 2023Article
- Cellular Stress: Modulator of Regulated Cell Death.Biology · 2023Review
- Affinity-Based Kinase-Catalyzed Crosslinking to Study Kinase-Substrate Pairs.Bioconjugate chemistry · 2023Article
- PKR induces TGF-β and limits oncolytic immune therapy.Journal for immunotherapy of cancer · 2023Article
- The role of p53 in anti-tumor immunity and response to immunotherapy.Frontiers in molecular biosciences · 2023Review
- PKR-Mediated Phosphorylation of eIF2a and CHK1 Is Associated with Doxorubicin-Mediated Apoptosis in HCC1143 Triple-Negative Breast Cancer Cells.International journal of molecular sciences · 2022Article
- PPM1D suppresses p53-dependent transactivation and cell death by inhibiting the Integrated Stress Response.Nature communications · 2022Article
- PACT promotes the metastasis of basal-like breast cancer through Rac1 SUMOylation and activation.Oncogene · 2022Article
- Article
- Mechanism of herpesvirus protein kinase UL13 in immune escape and viral replication.Frontiers in immunology · 2022Review
- Article
- Toxoplasma gondii secreted effectors co-opt host repressor complexes to inhibit necroptosis.Cell host & microbe · 2021Article
- Oncolytic Virotherapy: The Cancer Cell Side.Cancers · 2021Review
- Identification of key genes and pathways at the downstream of S100PBP in pancreatic cancer cells by integrated bioinformatical analysis.Translational cancer research · 2021Article
- Novel modulators of p53-signaling encoded by unknown genes of emerging viruses.PLoS pathogens · 2021Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type I IFN-induced expression of dsRNA-activated protein kinase (PKR) during viral infection is a well-established antiviral mechanism. However, little is known about the expression of PKR in the context of p53 and about PKR involvement in p53-mediated tumor suppression. Here, we report that PKR is a p53 target gene and plays an important role in the tumor-suppressor function of p53. Activation of p53 by genotoxic stress induces a significant level of PKR expression by acting on the newly identified cis-acting element (ISRE), which is separated from the IFN-stimulated responsive element on the PKR promoter, resulting in translational inhibition and cell apoptosis. The genotoxin-mediated inhibition of translation is associated with the p53/PKR/elF2a (eukaryotic initiation factor-2alpha) pathway. To some extent, p53 activation induced by DNA damage facilitates cell apoptosis by activating PKR. PKR-knockdown human colon cancer cells grew rapidly in nude mice and proved resistant to anti-cancer drugs. These data indicate that p53-mediated tumor suppression can be attributed at least in part to the biological functions of PKR induced by p53 in genotoxic conditions.
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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.