ArticleCell death and differentiation2017
Coordinated ubiquitination and phosphorylation of RIP1 regulates necroptotic cell death.
Article in Cell death and differentiation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 121 citations in OpenAlex.
- Unmasking programmed cell death in rhinovirus-driven asthma pathology.Biochemical Society transactions · 2026Review
- Countering postoperative immune suppression with a self-assembling dendritic cell nanovaccine.Bioactive materials · 2026Article
- HERC4-mediated ubiquitination licenses RIPK1 to initiate TNF-induced cell death.Nature structural & molecular biology · 2026Article
- Exosomal export of activated CASPASE-8 is linked to the prevention of TNF-induced cytotoxicity.Nature communications · 2026Article
- Ubiquitination and autophagy in host-pathogen interactions: from immune surveillance to therapeutic targeting.Nature reviews. Immunology · 2026Review
- Targeting MLKL-Driven Necroptosis: A Therapeutic Target in Inflammation and Host Defense.Biomolecules · 2026Review
- TAB2 controls a TAK1-independent cell death checkpoint at the level of TNFR1 complex II in the TNF pathway.Cell death and differentiation · 2026Article
- Necroptosis in cancer: insight from epigenetic, post-transcriptional and post-translational modifications.Journal of hematology & oncology · 2025Review
- A viral necrosome mediates direct RIPK3 activation to promote inflammatory necroptosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Exploring necroptosis: mechanistic analysis and antitumor potential of nanomaterials.Cell death discovery · 2025Review
- Inhibition of RIPK1 or RIPK3 kinase activity post ischemia-reperfusion reduces the development of chronic kidney injury.The Biochemical journal · 2025Article
- Deciphering Key Regulatory Roles of Linear Ubiquitination in Cell Fate Determination and Disease.Research (Washington, D.C.) · 2025Review
- An immunohistochemical atlas of necroptotic pathway expression.EMBO molecular medicine · 2024Article
- Mediators of necroptosis: from cell death to metabolic regulation.EMBO molecular medicine · 2024Review
- Diverse roles of UBE2S in cancer and therapy resistance: Biological functions and mechanisms.Heliyon · 2024Review
- Iron and copper: critical executioners of ferroptosis, cuproptosis and other forms of cell death.Cell communication and signaling : CCS · 2023Review
- Polarity protein AF6 functions as a modulator of necroptosis by regulating ubiquitination of RIPK1 in liver diseases.Cell death & disease · 2023Article
- LC3-independent autophagy is vital to prevent TNF cytotoxicity.Autophagy · 2023Article
- RIPK3 promoter hypermethylation in hepatocytes protects from bile acid-induced inflammation and necroptosis.Cell death & disease · 2023Article
- MLKL post-translational modifications: road signs to infection, inflammation and unknown destinations.Cell death and differentiation · 2023Review
13 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proper regulation of cell death signaling is crucial for the maintenance of homeostasis and prevention of disease. A caspase-independent regulated form of cell death called necroptosis is rapidly emerging as an important mediator of a number of human pathologies including inflammatory bowel disease and ischemia-reperfusion organ injury. Activation of necroptotic signaling through TNF signaling or organ injury leads to the activation of kinases receptor-interacting protein kinases 1 and 3 (RIP1 and RIP3) and culminates in inflammatory cell death. We found that, in addition to phosphorylation, necroptotic cell death is regulated by ubiquitination of RIP1 in the necrosome. Necroptotic RIP1 ubiquitination requires RIP1 kinase activity, but not necroptotic mediators RIP3 and MLKL (mixed lineage kinase-like). Using immunoaffinity enrichment and mass spectrometry, we profiled numerous ubiquitination events on RIP1 that are triggered during necroptotic signaling. Mutation of a necroptosis-related ubiquitination site on RIP1 reduced necroptotic cell death and RIP1 ubiquitination and phosphorylation, and disrupted the assembly of RIP1 and RIP3 in the necrosome, suggesting that necroptotic RIP1 ubiquitination is important for maintaining RIP1 kinase activity in the necrosome complex. We also observed RIP1 ubiquitination in injured kidneys consistent with a physiological role of RIP1 ubiquitination in ischemia-reperfusion disease. Taken together, these data reveal that coordinated and interdependent RIP1 phosphorylation and ubiquitination within the necroptotic complex regulate necroptotic signaling and cell death.
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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.