ArticleProceedings of the National Academy of Sciences of the United States of America2018
Regulation of a distinct activated RIPK1 intermediate bridging complex I and complex II in TNFα-mediated apoptosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 2 of them syntheses that pooled it.
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Who cites it
88 citing papers in PubMed, 2 syntheses or guidelines pooled it, 141 citations in OpenAlex.
- NEK1 mutations and the risk of amyotrophic lateral sclerosis (ALS): a meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021Pooled it
- Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target.Nature reviews. Drug discovery · 2020Pooled it
- GFH312 Reduces Neuronal Death by Inhibiting RIPK1-Mediated Apoptosis and Necroptosis After Ischemic Stroke.CNS neuroscience & therapeutics · 2026Article
- Disulfidptosis: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- TNK1 is a targetable JAK-independent driver of STAT signaling and inflammation.Genes & development · 2026Article
- RIPK1 regulates β-cell fate via actions on gene expression and kinase signaling in a mouse model of β-cell self-reactivity.Cell death & disease · 2026Article
- Targeting necroptosis: how does exercise protect against metabolic dysfunction-associated fatty liver disease?Frontiers in physiology · 2026Review
- EpCAM activates the ERK-EGR1 signaling axis and promotes TNF-α-induced the progression of anaplastic thyroid cancer.Journal of translational medicine · 2025Article
- Targeting tumor intrinsic TAK1 engages TNF-α-driven cell death through distinct mechanisms and enhances cancer immunotherapy.Cell death & disease · 2025Article
- The multiplex crosstalk between non-coding RNAs, programmed cell death and related mechanisms: a dynamic duo in hematological malignancies.Cancer cell international · 2025Review
- Specific signaling pathways mediated programmed cell death in tumor microenvironment and target therapies.Discover oncology · 2025Review
- The Role of Post-Translational Modifications in Necroptosis.Biomolecules · 2025Review
- Targeting necroptosis in Alzheimer's disease: can exercise modulate neuronal death?Frontiers in aging neuroscience · 2025Review
- Lactate attenuates PANoptosis and enhances ZBP-1 lactylation in macrophages in acute lung injury.Frontiers in immunology · 2025Article
- Article
- Significance of Programmed Cell Death Pathways in Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Blockade of IKK signaling induces RIPK1-independent apoptosis in human macrophages.PLoS pathogens · 2024Article
- Defective prelamin A processing promotes unconventional necroptosis driven by nuclear RIPK1.Nature cell biology · 2024Article
- Parkinson's disease models and death signaling: what do we know until now?Frontiers in neuroanatomy · 2024Review
- Emerging Microglial Therapies and Targets in Clinical Trial.Advances in neurobiology · 2024Review
28 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Stimulation of cells with TNFα can promote distinct cell death pathways, including RIPK1-independent apoptosis, necroptosis, and RIPK1-dependent apoptosis (RDA)-the latter of which we still know little about. Here we show that RDA involves the rapid formation of a distinct detergent-insoluble, highly ubiquitinated, and activated RIPK1 pool, termed "iuRIPK1." iuRIPK1 forms after RIPK1 activation in TNF-receptor-associated complex I, and before cytosolic complex II formation and caspase activation. To identify regulators of iuRIPK1 formation and RIPK1 activation in RDA, we conducted a targeted siRNA screen of 1,288 genes. We found that NEK1, whose loss-of-function mutations have been identified in 3% of ALS patients, binds to activated RIPK1 and restricts RDA by negatively regulating formation of iuRIPK1, while LRRK2, a kinase implicated in Parkinson's disease, promotes RIPK1 activation and association with complex I in RDA. Further, the E3 ligases APC11 and c-Cbl promote RDA, and c-Cbl is recruited to complex I in RDA, where it promotes prodeath K63-ubiquitination of RIPK1 to lead to iuRIPK1 formation. Finally, we show that two different modes of necroptosis induction by TNFα exist which are differentially regulated by iuRIPK1 formation. Overall, this work reveals a distinct mechanism of RIPK1 activation that mediates the signaling mechanism of RDA as well as a type of necroptosis.
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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.