ArticleCurrent biology : CB2008
CARP-2 is an endosome-associated ubiquitin ligase for RIP and regulates TNF-induced NF-kappaB activation.
Article in Current biology : CB, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29 citing papers in PubMed, 89 citations in OpenAlex.
- Endosome traffic in rheumatic diseases: mechanistic insights and therapeutic opportunities.Nature reviews. Rheumatology · 2026Review
- Genetically predicted triglyceride levels and endometriosis risk: Mendelian randomization with exploratory multi-omics analyses.PloS one · 2026Article
- Endosomal RFFL ubiquitin ligase regulates mitochondrial morphology by targeting mitofusin 2.Journal of cell science · 2025Article
- Ubiquitination and deubiquitination: Implications for the pathogenesis and treatment of osteoarthritis.Journal of orthopaedic translation · 2024Review
- Regulation of apoptosis by ubiquitination in liver cancer.American journal of cancer research · 2023Review
- Endosomal-associated RFFL facilitates mitochondrial clearance by enhancing PRKN/parkin recruitment to mitochondria.Autophagy · 2022Article
- The Ubiquitin Ligase RNF34 Participates in the Peripheral Quality Control of CFTR (RNF34 Role in CFTR PeriQC).Frontiers in molecular biosciences · 2022Article
- Roles for ADAM17 in TNF-R1 Mediated Cell Death and Survival in Human U937 and Jurkat Cells.Cells · 2021Article
- Classification models using circulating neutrophil transcripts can detect unruptured intracranial aneurysm.Journal of translational medicine · 2020Article
- Palmitoylation is required for TNF-R1 signaling.Cell communication and signaling : CCS · 2019Article
- Trafficking of the human ether-a-go-go-related gene (hERG) potassium channel is regulated by the ubiquitin ligase rififylin (RFFL).The Journal of biological chemistry · 2019Article
- Proteasome inhibition blocks necroptosis by attenuating death complex aggregation.Cell death & disease · 2018Article
- Cytokine Receptor Endocytosis: New Kinase Activity-Dependent and -Independent Roles of PI3K.Frontiers in endocrinology · 2017Review
- Angiotensin II down-regulates natriuretic peptide receptor-A expression and guanylyl cyclase activity in H9c2 (2-1) cardiac myoblast cells: Role of ROS and NF-κB.Molecular and cellular biochemistry · 2015Article
- Regulation of tumour necrosis factor signalling: live or let die.Nature reviews. Immunology · 2015Review
- Cell fate decisions regulated by K63 ubiquitination of tumor necrosis factor receptor 1.Molecular and cellular biology · 2014Article
- Rhbdd3 controls autoimmunity by suppressing the production of IL-6 by dendritic cells via K27-linked ubiquitination of the regulator NEMO.Nature immunology · 2014Article
- Screening for stress-resistance mutations in the mouse.Frontiers in genetics · 2014Article
- Altering the sphingolipid acyl chain composition prevents LPS/GLN-mediated hepatic failure in mice by disrupting TNFR1 internalization.Cell death & disease · 2013Article
- Membrane trafficking of death receptors: implications on signalling.International journal of molecular sciences · 2013Review
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11 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundThe proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) elicits cellular responses by signaling through a receptor complex that includes the essential adaptor molecule RIP. One important consequence of signaling is activation of the transcription factor NF-kappaB, and failure to downregulate TNF-induced NF-kappaB transcriptional activity results in chronic inflammation and death. Internalization of the receptor complex plays an important regulatory role in TNF signaling.
resultsWe report that CARP-2, a RING domain-containing ubiquitin protein ligase (E3), is a negative regulator of TNF-induced NF-kappaB activation. By virtue of its phospholipid-binding FYVE domain, CARP-2 localized to endocytic vesicles, where it interacted with internalized TNF-receptor complex, resulting in RIP ubiquitination and degradation. Knockdown of CARP-2 stabilized TNFR1-associated polyubiquitinated RIP levels after TNF simulation and enhanced activation of NF-kappaB.
conclusionsCARP-2 acts at the level of endocytic vesicles to limit the intensity of TNF-induced NF-kappaB activation by the regulated elimination of a necessary signaling component within the receptor complex.
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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.