ArticleCell research2014
Translocation of mixed lineage kinase domain-like protein to plasma membrane leads to necrotic cell death.
Article in Cell research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 459 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
459 citing papers in PubMed, 771 citations in OpenAlex.
- E3 ubiquitin ligase-mediated necroptosis: regulatory mechanisms and therapeutic implication in cancer.Molecular biology reports · 2026Review
- Article
- HERC4-mediated ubiquitination licenses RIPK1 to initiate TNF-induced cell death.Nature structural & molecular biology · 2026Article
- Neuroinflammation and Graft Survival in Pluripotent Stem Cell-Derived Therapies for the Central Nervous System.Journal of neurochemistry · 2026Review
- Review
- The dual role of RIPK family in IBD: from cell death to therapeutic targeting.Molecular medicine (Cambridge, Mass.) · 2026Review
- A non-classical necroptosis pathway mediated by caspases.Cell communication and signaling : CCS · 2026Article
- Arginine Di-methylation of RIP3 safeguards necroptosis for intestinal homeostasis.Cell death and differentiation · 2026Article
- Targeting non-apoptotic regulated cell death (RCD) to treat neurodegenerative diseases.Acta pharmaceutica Sinica. B · 2026Review
- Identification of key programmed cell death genes-necroptosis-related genes in systemic lupus erythematosus.Clinical and experimental medicine · 2026Article
- Regulation of lipid droplets accumulation by the Hippo-YAP/COX2 signaling pathway in neomycin-induced ototoxicity.Cell death discovery · 2026Article
- Programmed cell death in cancer: targeting necroptosis to kill tumor cell.Cell death discovery · 2026Review
- Early Detection of Cell Death Using Transmembrane Water Exchange Magnetic Resonance Imaging.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- TDP-43 pathology triggers neuroinflammation and cognitive impairment by inducing microglial necroptosis.EMBO molecular medicine · 2026Article
- Autoinhibitory control of MLKL governs pseudokinase domain phosphorylation and oligomerization during necroptosis.Cell reports · 2026Article
- Targeting MLKL-Driven Necroptosis: A Therapeutic Target in Inflammation and Host Defense.Biomolecules · 2026Review
- A viable kinase-inactive RIPK3 D143N mouse model reveals its scaffold function in driving TNF-induced inflammatory disorder.Cell death discovery · 2026Article
- Construction of Curcumin-Loaded Mesenchymal Stem Cell-Derived Exosomes and Their Mechanism in Inhibiting Pyroptosis During Hepatic Ischemia-Reperfusion Injury.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Cell death and its interaction with mitochondrial dysfunction in pathogenesis of acute pancreatitis: a comprehensive review.Apoptosis : an international journal on programmed cell death · 2026Review
- Immune Aging as a Failure of Programmed Cell Death Coordination.International journal of molecular sciences · 2026Review
399 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mixed lineage kinase domain-like protein (MLKL) was identified to function downstream of receptor interacting protein 3 (RIP3) in tumor necrosis factor-α (TNF)-induced necrosis (also called necroptosis). However, how MLKL functions to mediate necroptosis is unknown. By reconstitution of MLKL function in MLKL-knockout cells, we showed that the N-terminus of MLKL is required for its function in necroptosis. The oligomerization of MLKL in TNF-treated cells is essential for necroptosis, as artificially forcing MLKL together by using the hormone-binding domain (HBD*) triggers necroptosis. Notably, forcing together the N-terminal domain (ND) but not the C-terminal kinase domain of MLKL causes necroptosis. Further deletion analysis showed that the four-α-helix bundle of MLKL (1-130 amino acids) is sufficient to trigger necroptosis. Both the HBD*-mediated and TNF-induced complexes of MLKL(ND) or MLKL are tetramers, and translocation of these complexes to lipid rafts of the plasma membrane precedes cell death. The homo-oligomerization is required for MLKL translocation and the signal sequence for plasma membrane location is located in the junction of the first and second α-helices of MLKL. The plasma membrane translocation of MLKL or MLKL(ND) leads to sodium influx, and depletion of sodium from the cell culture medium inhibits necroptosis. All of the above phenomena were not seen in apoptosis. Thus, the MLKL oligomerization leads to translocation of MLKL to lipid rafts of plasma membrane, and the plasma membrane MLKL complex acts either by itself or via other proteins to increase the sodium influx, which increases osmotic pressure, eventually leading to membrane rupture.
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.