ArticleCell death and differentiation2016
K45A mutation of RIPK1 results in poor necroptosis and cytokine signaling in macrophages, which impacts inflammatory responses in vivo.
Article in Cell death and differentiation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed.
- Activation of RIPK3 drives PANoptosis in human cells and inflammatory apoptosis in canine cells dependent on RIPK1, FADD and caspases.Apoptosis : an international journal on programmed cell death · 2026Article
- Allosteric targeting of RIPK1: discovery of novel inhibitorsRSC medicinal chemistry · 2025Article
- Pak4-mediated crosstalk between necroptotic macrophages and tendon stem/progenitor cells contributes to traumatic heterotopic ossification formation.Bone research · 2025Article
- Single-cell RNA-seq combined with bulk RNA-seq analysis identifies necroptosis-related genes as therapeutic targets for periodontitis.BMC medical genomics · 2025Article
- Regulation of Zfp36 by ISGF3 and MK2 restricts the expression of inflammatory cytokines during necroptosis stimulation.Cell death & disease · 2024Article
- Article
- The interaction between RIPK1 and FADD controls perinatal lethality and inflammation.Cell reports · 2024Article
- Acute lung injury: a view from the perspective of necroptosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Review
- RIPK1 activation in Mecp2-deficient microglia promotes inflammation and glutamate release in RTT.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Roles of RIPK1 as a stress sentinel coordinating cell survival and immunogenic cell death.Nature reviews. Molecular cell biology · 2023Review
- Vemurafenib inhibits necroptosis in normal and pathological conditions as a RIPK1 antagonist.Cell death & disease · 2023Article
- RIPK1 is aberrantly expressed in multiple B-cell cancers and implicated in the underlying pathogenesis.Discover oncology · 2023Article
- Article
- Repurposing of the FGFR inhibitor AZD4547 as a potent inhibitor of necroptosis by selectively targeting RIPK1.Acta pharmacologica Sinica · 2023Article
- RIPK1 in the inflammatory response and sepsis: Recent advances, drug discovery and beyond.Frontiers in immunology · 2023Review
- Necroptosis in heart disease: Molecular mechanisms and therapeutic implications.Journal of molecular and cellular cardiology · 2022Review
- Emerging therapies to target CNS pathophysiology in multiple sclerosis.Nature reviews. Neurology · 2022Review
- Regulated necrosis, a proinflammatory cell death, potentially counteracts pathogenic infections.Cell death & disease · 2022Review
- No Time to Die: How Kidney Cancer Evades Cell Death.International journal of molecular sciences · 2022Review
- Receptor interacting protein 3 kinase, not 1 kinase, through MLKL-mediated necroptosis is involved in UVA-induced corneal endothelium cell death.Cell death discovery · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
Receptor interacting protein kinase 1 (RIPK1) participates in several cell signaling complexes that promote cell activation and cell death. Stimulation of RIPK1 in the absence of caspase signaling induces regulated necrosis (necroptosis), which promotes an inflammatory response. Understanding of the mechanisms through which RIPK1 promotes inflammation has been unclear. Herein we have evaluated the impact of a K45A mutation of RIPK1 on necroptosis of macrophages and the activation of inflammatory response. We show that K45A mutation of RIPK1 results in attenuated necroptosis of macrophages in response to stimulation with LPS, TNFα and IFNβ in the absence of caspase signaling. Impairment in necroptosis correlated with poor phosphorylation of RIPK1, RIPK3 and reduced trimerization of MLKL. Furthermore, K45A mutation of RIPK1 resulted in poor STAT1 phosphorylation (at S727) and expression of RANTES and MIP-1α following TNF-R engagement in the absence of caspase activation. Our results further indicate that in the absence of stimulation by pathogen-associated molecular patterns (PAMPs), cellular inhibitors of apoptotic proteins (cIAPs) prevent the K45-dependent auto-phosphorylation of RIPK1, leading to resistance against necroptosis. Finally, RIPK1(K45A) mice displayed attenuated inflammatory response in vivo as they were significantly resistant against endotoxin shock, but highly susceptible against a challenge with Salmonella typhimurium. This correlated with reduced expression of IL-1β and ROS, and poor processing of caspase 8 by RIPK1(K45A) macrophages. Overall, these results indicate that K45 mediated kinase activity of RIPK1 is not only important for necroptosis but it also has a key role in promoting cytokine signaling and host response to inflammatory stimuli.
Indexed as
Identifiers
What OpenQuestion holds
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 OpenQuestion graph.