ArticleThe EMBO journal2012
Rsk-mediated phosphorylation and 14-3-3ɛ binding of Apaf-1 suppresses cytochrome c-induced apoptosis.
Article in The EMBO journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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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
26 citing papers in PubMed, 51 citations in OpenAlex.
- Review
- Spatial Transcriptomics in Thyroid Cancer: Applications, Limitations, and Future Perspectives.Cells · 2025Review
- A cell wall-associated kinase phosphorylates NLR immune receptor to negatively regulate resistosome formation.Nature plants · 2025Article
- Ribosomal S6 kinase signaling regulates neuronal viability during development and confers resistance to excitotoxic cell death in mature neurons.Neuroscience · 2024Article
- circSORBS1 inhibits lung cancer progression by sponging miR-6779-5p and directly binding RUFY3 mRNA.Journal of translational medicine · 2024Article
- Caspase 3-specific cleavage of MEK1 suppresses ERK signaling and sensitizes cells to stress-induced apoptosis.FEBS open bio · 2023Article
- Fusion genes in gynecologic tumors: the occurrence, molecular mechanism and prospect for therapy.Cell death & disease · 2021Review
- Costunolide attenuates oxygen‑glucose deprivation/reperfusion‑induced mitochondrial‑mediated apoptosis in PC12 cells.Molecular medicine reports · 2021Article
- The impact of phosphatases on proliferative and survival signaling in cancer.Cellular and molecular life sciences : CMLS · 2018Review
- Cytochrome c speeds up caspase cascade activation by blocking 14-3-3ε-dependent Apaf-1 inhibition.Cell death & disease · 2018Article
- Reversal of homocysteine-induced neurotoxicity in rat hippocampal neurons by astaxanthin: evidences for mitochondrial dysfunction and signaling crosstalk.Cell death discovery · 2018Article
- Vaccinia Virus Encodes a Novel Inhibitor of Apoptosis That Associates with the Apoptosome.Journal of virology · 2017Article
- Isoimperatorin induces apoptosis of the SGC-7901 human gastric cancer cell line via the mitochondria-mediated pathway.Oncology letters · 2017Article
- Article
- Protective Roles of N-acetyl Cysteine and/or Taurine against Sumatriptan-Induced Hepatotoxicity.Advanced pharmaceutical bulletin · 2016Article
- Signal transduction in cancer.Cold Spring Harbor perspectives in medicine · 2015Review
- Protein expression profiling in head fragments during planarian regeneration after amputation.Development genes and evolution · 2015Article
- DNA damage-induced nuclear translocation of Apaf-1 is mediated by nucleoporin Nup107.Cell cycle (Georgetown, Tex.) · 2015Article
- A systems biology analysis of apoptosome formation and apoptosis execution supports allosteric procaspase-9 activation.The Journal of biological chemistry · 2014Article
- From computational modelling of the intrinsic apoptosis pathway to a systems-based analysis of chemotherapy resistance: achievements, perspectives and challenges in systems medicine.Cell death & disease · 2014Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Many pro-apoptotic signals trigger mitochondrial cytochrome c release, leading to caspase activation and ultimate cellular breakdown. Cell survival pathways, including the mitogen-activated protein kinase (MAPK) cascade, promote cell viability by impeding mitochondrial cytochrome c release and by inhibiting subsequent caspase activation. Here, we describe a mechanism for the inhibition of cytochrome c-induced caspase activation by MAPK signalling, identifying a novel mode of apoptotic regulation exerted through Apaf-1 phosphorylation by the 90-kDa ribosomal S6 kinase (Rsk). Recruitment of 14-3-3ɛ to phosphorylated Ser268 impedes the ability of cytochrome c to nucleate apoptosome formation and activate downstream caspases. High endogenous levels of Rsk in PC3 prostate cancer cells or Rsk activation in other cell types promoted 14-3-3ɛ binding to Apaf-1 and rendered the cells insensitive to cytochrome c, suggesting a potential role for Rsk signalling in apoptotic resistance of prostate cancers and other cancers with elevated Rsk activity. Collectively, these results identify a novel locus of apoptosomal regulation wherein MAPK signalling promotes Rsk-catalysed Apaf-1 phosphorylation and consequent binding of 14-3-3ɛ, resulting in decreased cellular responsiveness to cytochrome c.
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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 Socratic graph.