ArticleOncogene2018
K6 linked polyubiquitylation of FADD by CHIP prevents death inducing signaling complex formation suppressing cell death.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- Cathepsin L deletion enhances sensitivity to anticancer drugs through Parkin-mediated ubiquitination of Bcl-xL and USP53-induced Survivin destabilization.Cell death and differentiation · 2026Article
- Acupuncture-induced HSP70 upregulation in neuroprotection: mitochondrial and anti-apoptotic mechanisms.American journal of translational research · 2026Review
- Opposing regulation of the K63-linked polyubiquitination of RIPK3 by SMURF1 and USP5 in necroptosis.Nature communications · 2025Article
- The Role of Post-Translational Modifications in Necroptosis.Biomolecules · 2025Review
- Hypoxia-mediated SUMOylation of FADD exacerbates endothelial cell injury via the RIPK1-RIPK3-MLKL signaling axis.Cell death & disease · 2025Article
- MicroRNAs regulating apoptosis and delivery strategies for treating intervertebral disc degeneration.Frontiers in cell and developmental biology · 2025Review
- Insights into the regulation of CHIP E3 ligase-mediated ubiquitination of neuronal protein BNIP-H.PNAS nexus · 2024Article
- Review
- BAP1 controls mesenchymal stem cell migration by inhibiting the ERK signaling pathway.BMB reports · 2024Article
- Article
- Phosphorylation of OTUB1 at Tyr 26 stabilizes the mTORC1 component, Raptor.Cell death and differentiation · 2023Article
- Regulation of apoptosis by ubiquitination in liver cancer.American journal of cancer research · 2023Review
- FADD as a key molecular player in cancer progression.Molecular medicine (Cambridge, Mass.) · 2022Review
- Chaperone-assisted E3 ligase CHIP: A double agent in cancer.Genes & diseases · 2022Review
- BAP1 phosphorylation-mediated Sp1 stabilization plays a critical role in cathepsin K inhibition-induced C-terminal p53-dependent Bax upregulation.Redox biology · 2022Article
- BMP-6 Attenuates Oxygen and Glucose Deprivation-Induced Apoptosis in Human Neural Stem Cells through Inhibiting p38 MAPK Signaling Pathway.International journal of stem cells · 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
- CHIP and BAP1 Act in Concert to Regulate INO80 Ubiquitination and Stability for DNA Replication.Molecules and cells · 2021Article
- Targeted therapy for intervertebral disc degeneration: inhibiting apoptosis is a promising treatment strategy.International journal of medical sciences · 2021Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fas-associated death domain (FADD) is an adaptor protein recruiting complexes of caspase 8 to death ligand receptors to induce extrinsic apoptotic cell death in response to a TNF superfamily member. Although, formation of the complex of FADD and caspase 8 upon death stimuli has been studied in detail, posttranslational modifications fine-tuning these processes have yet to be identified. Here we revealed that K6-linked polyubiquitylation of FADD on lysines 149 and 153 mediated by C terminus HSC70-interacting protein (CHIP) plays an important role in preventing formation of the death inducing signaling complex (DISC), thus leading to the suppression of cell death. Cells depleted of CHIP showed higher sensitivity toward death ligands such as FasL and TRAIL, leading to upregulation of DISC formation composed of a death receptor, FADD, and caspase 8. CHIP was able to bind to FADD, induce K6-linked polyubiquitylation of FADD, and suppress DISC formation. By mass spectrometry, lysines 149 and 153 of FADD were found to be responsible for CHIP-mediated FADD ubiquitylation. FADD mutated at these sites was capable of more potent cell death induction as compared with the wild type and was no longer suppressed by CHIP. On the other hand, CHIP deficient in E3 ligase activity was not capable of suppressing FADD function and of FADD ubiquitylation. CHIP depletion in ME-180 cells induced significant sensitization of these cells toward TRAIL in xenograft analyses. These results imply that K6-linked ubiquitylation of FADD by CHIP is a crucial checkpoint in cytokine-dependent extrinsic apoptosis.
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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.