ArticleCell death & disease2024
LUBAC-mediated M1 Ub regulates necroptosis by segregating the cellular distribution of active MLKL.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Necroptosis triggers inflammatory interferon signatures in patient-derived metastatic breast cancer organoids.Signal transduction and targeted therapy · 2026Article
- IAPs in cancers: molecular mechanisms, clinical prognostic value, and translational therapeutic potential.Journal of translational medicine · 2026Review
- USP39 inhibits MLKL phosphorylation and deubiquitination to suppress necroptosis of nucleus pulposus cells and attenuate intervertebral disc degeneration.Journal of orthopaedic translation · 2026Article
- Association of peripheral blood LUBAC and OTULIN expression with severity and outcome in acute ischemic stroke: a prospective cohort study.Frontiers in immunology · 2026Article
- Loss of ADAM15 prevents necroptosis induction by partial RIPK1 degradation due to enhanced TNF-R1 surface expression and basal caspase-8 activation.Cell communication and signaling : CCS · 2025Article
- The Role of Post-Translational Modifications in Necroptosis.Biomolecules · 2025Review
- Advances in the Study of Necroptosis in Vascular Dementia: Focus on Blood-Brain Barrier and Neuroinflammation.CNS neuroscience & therapeutics · 2025Review
- Deciphering Key Regulatory Roles of Linear Ubiquitination in Cell Fate Determination and Disease.Research (Washington, D.C.) · 2025Review
- Inhibitors identify an auxiliary role for mTOR signalling in necroptosis execution downstream of MLKL activation.The Biochemical journal · 2024Article
- Acute lung injury: a view from the perspective of necroptosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Review
- Silibinin Induces Both Apoptosis and Necroptosis with Potential Anti-tumor Efficacy in Lung Cancer.Anti-cancer agents in medicinal chemistry · 2024Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Plasma membrane accumulation of phosphorylated mixed lineage kinase domain-like (MLKL) is a hallmark of necroptosis, leading to membrane rupture and inflammatory cell death. Pro-death functions of MLKL are tightly controlled by several checkpoints, including phosphorylation. Endo- and exocytosis limit MLKL membrane accumulation and counteract necroptosis, but the exact mechanisms remain poorly understood. Here, we identify linear ubiquitin chain assembly complex (LUBAC)-mediated M1 poly-ubiquitination (poly-Ub) as novel checkpoint for necroptosis regulation downstream of activated MLKL in cells of human origin. Loss of LUBAC activity inhibits tumor necrosis factor α (TNFα)-mediated necroptosis, not by affecting necroptotic signaling, but by preventing membrane accumulation of activated MLKL. Finally, we confirm LUBAC-dependent activation of necroptosis in primary human pancreatic organoids. Our findings identify LUBAC as novel regulator of necroptosis which promotes MLKL membrane accumulation in human cells and pioneer primary human organoids to model necroptosis in near-physiological settings.
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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.