ArticleCell death & disease2016
HSP90 activity is required for MLKL oligomerisation and membrane translocation and the induction of necroptotic cell death.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed, 154 citations in OpenAlex.
- Identification of human MLKL Cys184 and HSPBP1 Cys201 as novel cellular targets for necroptosis.Cell death & disease · 2026Article
- Autoinhibitory control of MLKL governs pseudokinase domain phosphorylation and oligomerization during necroptosis.Cell reports · 2026Article
- Celastrol ameliorates ulcerative colitis by inhibiting HSP90-mediated necroptosis of intestinal epithelial cells.Frontiers in pharmacology · 2026Article
- The mechanisms by which free heme exacerbates sepsis and the potential therapeutic targets.Frontiers in immunology · 2026Review
- 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
- Mixed Lineage Kinase Domain-Like Protein (MLKL): From Mechanisms to Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- PANoptosis: a potential target of atherosclerotic cardiovascular disease.Apoptosis : an international journal on programmed cell death · 2025Review
- Ferroptosis-activating metabolite acrolein antagonizes necroptosis and anti-cancer therapeutics.Nature communications · 2025Article
- Specific signaling pathways mediated programmed cell death in tumor microenvironment and target therapies.Discover oncology · 2025Review
- Construction and validation of a cell death-related genes prognosis signature of hepatocellular carcinoma.Translational cancer research · 2025Article
- MLKL-USP7-UBA52 signaling is indispensable for autophagy in brain through maintaining ubiquitin homeostasis.Autophagy · 2025Article
- T817MA attenuates oxidative stress and ER stress via the HSP70-HSP90 pathway after brain ischemiaFrontiers in pharmacology · 2025Article
- Finding differentially expressed genes between cell fates predicted by image-based deep learning.Biophysics and physicobiology · 2025Article
- Gambogic acid targets HSP90 to alleviate DSS-induced colitis via inhibiting the necroptosis of intestinal epithelial cells.Frontiers in pharmacology · 2025Article
- Mechanisms and cross-talk of regulated cell death and their epigenetic modifications in tumor progression.Molecular cancer · 2024Review
- Emerging roles of senolytics/senomorphics in HIV-related co-morbidities.Biochemical pharmacology · 2024Review
- Inhibitors identify an auxiliary role for mTOR signalling in necroptosis execution downstream of MLKL activation.The Biochemical journal · 2024Article
- Osteogenesis imperfecta type 10 and the cellular scaffolds underlying common immunological diseases.Genes and immunity · 2024Review
- The necroptosis cell death pathway drives neurodegeneration in Alzheimer's disease.Acta neuropathologica · 2024Review
- Acute lung injury: a view from the perspective of necroptosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Review
39 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Necroptosis is a caspase-independent form of regulated cell death that has been implicated in the development of a range of inflammatory, autoimmune and neurodegenerative diseases. The pseudokinase, Mixed Lineage Kinase Domain-Like (MLKL), is the most terminal known obligatory effector in the necroptosis pathway, and is activated following phosphorylation by Receptor Interacting Protein Kinase-3 (RIPK3). Activated MLKL translocates to membranes, leading to membrane destabilisation and subsequent cell death. However, the molecular interactions governing the processes downstream of RIPK3 activation remain poorly defined. Using a phenotypic screen, we identified seven heat-shock protein 90 (HSP90) inhibitors that inhibited necroptosis in both wild-type fibroblasts and fibroblasts expressing an activated mutant of MLKL. We observed a modest reduction in MLKL protein levels in human and murine cells following HSP90 inhibition, which was only apparent after 15 h of treatment. The delayed reduction in MLKL protein abundance was unlikely to completely account for defective necroptosis, and, consistent with this, we also found inhibition of HSP90 blocked membrane translocation of activated MLKL. Together, these findings implicate HSP90 as a modulator of necroptosis at the level of MLKL, a function that complements HSP90's previously demonstrated modulation of the upstream necroptosis effector kinases, RIPK1 and RIPK3.
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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.