ArticleThe Journal of biological chemistry2018
Linear ubiquitination of cFLIP induced by LUBAC contributes to TNFα-induced apoptosis.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 46 citations in OpenAlex.
- Opening the black box: insights into ubiquitin-mediated control of innate antiviral immunity and AI-enhanced therapeutics.Frontiers in immunology · 2026Review
- Evolution of the conformational ensemble and allosteric networks of apoptotic caspases in chordates.The Biochemical journal · 2025Article
- The Role of Post-Translational Modifications in Necroptosis.Biomolecules · 2025Review
- Ubiquitination Enzymes in Cancer, Cancer Immune Evasion, and Potential Therapeutic Opportunities.Cells · 2025Review
- Deciphering Key Regulatory Roles of Linear Ubiquitination in Cell Fate Determination and Disease.Research (Washington, D.C.) · 2025Review
- Review
- Met1-linked ubiquitination in cell signaling regulation.Biophysics reports · 2024Article
- N4BP1 functions as a dimerization-dependent linear ubiquitin reader which regulates TNF signalling.Cell death discovery · 2024Article
- Mechanisms underlying linear ubiquitination and implications in tumorigenesis and drug discovery.Cell communication and signaling : CCS · 2023Review
- The mechanism of linear ubiquitination in regulating cell death and correlative diseases.Cell death & disease · 2023Review
- Review
- Regulation of apoptosis by ubiquitination in liver cancer.American journal of cancer research · 2023Review
- HOIP modulates the stability of GPx4 by linear ubiquitination.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- PP6 negatively modulates LUBAC-mediated M1-ubiquitination of RIPK1 and c-FLIPCell death & disease · 2022Article
- Restoring TRAILR2/DR5-Mediated Activation of Apoptosis upon Endoplasmic Reticulum Stress as a Therapeutic Strategy in Cancer.International journal of molecular sciences · 2022Review
- Loss of Rnf31 and Vps4b sensitizes pancreatic cancer to T cell-mediated killing.Nature communications · 2022Article
- The deubiquitinase Usp27x as a novel regulator of cFLIPApoptosis : an international journal on programmed cell death · 2022Article
- The role of Ubiquitination in Apoptosis and Necroptosis.Cell death and differentiation · 2022Review
- Emerging Roles of Non-proteolytic Ubiquitination in Tumorigenesis.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The linear ubiquitin chain assembly complex (LUBAC) regulates NF-κB activation by modifying proteins with linear (M1-linked) ubiquitination chains. Although LUBAC also regulates the apoptosis pathway, the precise mechanism by which LUBAC regulates apoptosis remains not fully defined. Here, we report that LUBAC-mediated M1-linked ubiquitination of cellular FLICE-like inhibitory protein (cFLIP), an anti-apoptotic molecule, contributes to tumor necrosis factor (TNF) α-induced apoptosis. We found that deficiency of RNF31, the catalytic subunit of the LUBAC complex, promoted cFLIP degradation in a proteasome-dependent manner. Moreover, we observed RNF31 directly interact with cFLIP, and LUBAC further conjugated M1-linked ubiquitination chains at Lys-351 and Lys-353 of cFLIP to stabilize cFLIP, thereby protecting cells from TNFα-induced apoptosis. Together, our study identifies a new substrate of LUBAC and reveals a new molecular mechanism through which LUBAC regulates TNFα-induced apoptosis via M1-linked ubiquitination.
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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 OpenQuestion graph.