ArticleMolecular and cellular biology2009
Unscheduled Akt-triggered activation of cyclin-dependent kinase 2 as a key effector mechanism of apoptin's anticancer toxicity.
Article in Molecular and cellular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 69 citations in OpenAlex.
- Silencing of IRF8 Mediated by m6A Modification Promotes the Progression of T-Cell Acute Lymphoblastic Leukemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- The Role of Apoptin in Chicken Anemia Virus Replication.Pathogens (Basel, Switzerland) · 2020Review
- Apoptosis Triggered by ORF3 Proteins of theFrontiers in cellular and infection microbiology · 2020Review
- Apoptin as a Tumor-Specific Therapeutic Agent: Current Perspective on Mechanism of Action and Delivery Systems.Frontiers in cell and developmental biology · 2020Review
- Cancer Treatment Goes Viral: Using Viral Proteins to Induce Tumour-Specific Cell Death.Cancers · 2019Review
- IRF8 induces senescence of lung cancer cells to exert its tumor suppressive function.Cell cycle (Georgetown, Tex.) · 2019Article
- Integrated Proteomics Reveals Apoptosis-related Mechanisms Associated with Placental Malaria.Molecular & cellular proteomics : MCP · 2019Article
- Marek's disease virus oncoprotein Meq physically interacts with the chicken infectious anemia virus-encoded apoptotic protein apoptin.Oncotarget · 2018Article
- Rewiring of the apoptotic TGF-β-SMAD/NFκB pathway through an oncogenic function of p27 in human papillary thyroid cancer.Oncogene · 2017Article
- Activation of the Chicken Anemia Virus Apoptin Protein by Chk1/2 Phosphorylation Is Required for Apoptotic Activity and Efficient Viral Replication.Journal of virology · 2016Article
- Network-level effects of kinase inhibitors modulate TNF-α-induced apoptosis in the intestinal epithelium.Science signaling · 2015Article
- Genetic deletion and pharmacological inhibition of Akt1 isoform attenuates bladder cancer cell proliferation, motility and invasion.European journal of pharmacology · 2015Article
- Viral genes as oncolytic agents for cancer therapy.Cellular and molecular life sciences : CMLS · 2015Review
- Article
- Nuclear localized Akt enhances breast cancer stem-like cells through counter-regulation of p21(Waf1/Cip1) and p27(kip1).Cell cycle (Georgetown, Tex.) · 2015Article
- Nuclear Akt: target for breast cancer therapy?Cell cycle (Georgetown, Tex.) · 2015Article
- Pemetrexed induces S-phase arrest and apoptosis via a deregulated activation of Akt signaling pathway.PloS one · 2014Article
- ROS-mediated activation of AKT induces apoptosis via pVHL in prostate cancer cells.Molecular and cellular biochemistry · 2013Article
- Apoptin selectively induces the apoptosis of tumor cells by suppressing the transcription of HSP70.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2013Article
- Salmonella typhimurium mediated delivery of Apoptin in human laryngeal cancer.International journal of medical sciences · 2013Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 4 countries.
Funding
Abstract
Apoptin, a protein from the chicken anemia virus, has attracted attention because it specifically kills tumor cells while leaving normal cells unharmed. The reason for this tumor selectivity is unclear and depends on subcellular localization, as apoptin resides in the cytoplasm of normal cells but in the nuclei of transformed cells. It was shown that nuclear localization and tumor-specific killing crucially require apoptin's phosphorylation by an as yet unknown kinase. Here we elucidate the pathway of apoptin-induced apoptosis and show that it essentially depends on abnormal phosphatidylinositol 3-kinase (PI3-kinase)/Akt activation, resulting in the activation of the cyclin-dependent kinase CDK2. Inhibitors as well as dominant-negative mutants of PI3-kinase and Akt not only inhibited CDK2 activation but also protected cells from apoptin-induced cell death. Akt activated CDK2 by direct phosphorylation as well as by the phosphorylation-induced degradation of the inhibitor p27(Kip1). Importantly, we also identified CDK2 as the principal kinase that phosphorylates apoptin and is crucially required for apoptin-induced cell death. Immortalized CDK2-deficient fibroblasts and CDK2 knockdown cells were markedly protected against apoptin. Thus, our results not only decipher the pathway of apoptin-induced cell death but also provide mechanistic insights for the selective killing of tumor cells.
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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.