ArticleProceedings of the National Academy of Sciences of the United States of America2015
A cytosolic heat shock protein 90 and cochaperone CDC37 complex is required for RIP3 activation during necroptosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 161 citations in OpenAlex.
- Eupalinolide B Ameliorates Diabetic Kidney Disease via Inhibition of Cell Division Cycle 37-Mediated Inflammatory Pathways.Journal of the American Society of Nephrology : JASN · 2026Article
- Functional amyloids as molecular switches: emerging roles in diverse signalling pathways.Biochemical Society transactions · 2026Review
- Species-specific regulation of necroptosis by STK38-dependent RIPK1 phosphorylation.Cell death and differentiation · 2026Article
- Autoinhibitory control of MLKL governs pseudokinase domain phosphorylation and oligomerization during necroptosis.Cell reports · 2026Article
- Amygdalin synergizes with the TNF-α monoclonal antibody infliximab to modulate HSP90 and related necro-inflammatory/oxidative stress pathways in a rat model of hepatic I/R.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Circulating and Respiratory Biomarkers in Sepsis-Induced ARDS: Diagnostic and Prognostic Insights - A Narrative Review.Journal of inflammation research · 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
- Trigger Points of Necroptosis (RIPK1, RIPK3, and MLKL)-Promising Horizon or Blind Alley in Therapy of Colorectal Cancer?International journal of molecular sciences · 2025Review
- Polymorphisms in Necroptosis Pathway Genes: Novel Prognostic Markers for Multiple Myeloma Treatment Outcomes.International journal of molecular sciences · 2025Article
- Necroptosis-based glioblastoma prognostic subtypes: implications for TME remodeling and therapy response.Annals of medicine · 2024Article
- 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
- RIPK3 signaling and its role in regulated cell death and diseases.Cell death discovery · 2024Review
- The crosstalk between mitochondrial quality control and metal-dependent cell death.Cell death & disease · 2024Review
- Necroptosis inhibitors: mechanisms of action and therapeutic potential.Apoptosis : an international journal on programmed cell death · 2024Review
- Prognostic Impact of Heat Shock Protein 90 Expression in Women Diagnosed with Cervical Cancer.International journal of molecular sciences · 2024Article
- HSP90 multi-functionality in cancer.Frontiers in immunology · 2024Review
- Dichotomous roles of RIPK3 in regulating the IFN response and NLRP3 inflammasome in human monocytes.Journal of leukocyte biology · 2023Article
- LncRNA MALAT1 Promoted Neuronal Necroptosis in Cerebral Ischemia-reperfusion Mice by Stabilizing HSP90.Neurochemical research · 2023Article
45 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Receptor-interacting protein kinase 3, RIP3, and a pseudokinase mixed lineage kinase-domain like protein, MLKL, constitute the core components of the necroptosis pathway, which causes programmed necrotic death in mammalian cells. Latent RIP3 in the cytosol is activated by several upstream signals including the related kinase RIP1, which transduces signals from the tumor necrosis factor (TNF) family of cytokines. We report here that RIP3 activation following the induction of necroptosis requires the activity of an HSP90 and CDC37 cochaperone complex. This complex physically associates with RIP3. Chemical inhibitors of HSP90 efficiently block necroptosis by preventing RIP3 activation. Cells with knocked down CDC37 were unable to respond to necroptosis stimuli. Moreover, an HSP90 inhibitor that is currently under clinical development as a cancer therapy was able to prevent systemic inflammatory response syndrome in rats treated with TNF-α. HSP90 and CDC37 cochaperone complex-mediated protein folding is thus an important part of the RIP3 activation process during necroptosis.
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