ArticleEMBO reports2021
USP22 controls necroptosis by regulating receptor-interacting protein kinase 3 ubiquitination.
Article in EMBO reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 75 citations in OpenAlex.
- Step-brothers in arms, SAGA and ATAC co-activator complexes, use different strategies.The EMBO journal · 2026Review
- USP22 suppresses trophoblast cell necroptosis in preeclampsia by stabilizing KAT2A-mediated histone acetylation at the SFRP1 promoter.Journal of translational medicine · 2026Article
- SMARCD1 and Its Functional Relevance in SWI/SNF and Cancer.International journal of molecular sciences · 2026Review
- Roles of ubiquitin‑specific peptidase 22 in cellular fate: From embryonic survival to tissue repair, inflammation and metabolism (Review).International journal of molecular medicine · 2026Review
- Decoding the Oncogenic Role of USP22 Through Pan-Cancer Genomic and Epigenetic Analysis.Cancer reports (Hoboken, N.J.) · 2026Article
- USP13 depletion sensitizes colorectal cancer cells to necroptosis by destabilizing cIAP2 proteins.Cell death and differentiation · 2026Article
- Targeting ubiquitin-specific peptidase 22 in solid tumours: from ubiquitination to immunotherapy.Frontiers in cell and developmental biology · 2026Review
- The functional landscape of the human ubiquitinome.bioRxiv : the preprint server for biology · 2025Article
- Opposing regulation of the K63-linked polyubiquitination of RIPK3 by SMURF1 and USP5 in necroptosis.Nature communications · 2025Article
- Necroptosis in cancer: insight from epigenetic, post-transcriptional and post-translational modifications.Journal of hematology & oncology · 2025Review
- Linear ubiquitination at damaged lysosomes induces local NFKB activation and controls cell survival.Autophagy · 2025Article
- The Role of Post-Translational Modifications in Necroptosis.Biomolecules · 2025Review
- Deubiquitinating enzymes: Key regulators of ferroptosis and pyroptosis and novel targets for cancer intervention.International journal of biological sciences · 2025Review
- Necroptosis-based glioblastoma prognostic subtypes: implications for TME remodeling and therapy response.Annals of medicine · 2024Article
- Mechanisms and cross-talk of regulated cell death and their epigenetic modifications in tumor progression.Molecular cancer · 2024Review
- Necroptosis-related lncRNAs: biomarkers for predicting prognosis and immune response in lung adenocarcinoma.Translational lung cancer research · 2024Article
- Caspase-8 in inflammatory diseases: a potential therapeutic target.Cellular & molecular biology letters · 2024Review
- Inhibitors identify an auxiliary role for mTOR signalling in necroptosis execution downstream of MLKL activation.The Biochemical journal · 2024Article
- Targeting necroptosis: a promising avenue for respiratory disease treatment.Cell communication and signaling : CCS · 2024Review
- Let's make it personal: CRISPR tools in manipulating cell death pathways for cancer treatment.Cell biology and toxicology · 2024Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dynamic control of ubiquitination by deubiquitinating enzymes is essential for almost all biological processes. Ubiquitin-specific peptidase 22 (USP22) is part of the SAGA complex and catalyzes the removal of mono-ubiquitination from histones H2A and H2B, thereby regulating gene transcription. However, novel roles for USP22 have emerged recently, such as tumor development and cell death. Apart from apoptosis, the relevance of USP22 in other programmed cell death pathways still remains unclear. Here, we describe a novel role for USP22 in controlling necroptotic cell death in human tumor cell lines. Loss of USP22 expression significantly delays TNFα/Smac mimetic/zVAD.fmk (TBZ)-induced necroptosis, without affecting TNFα-mediated NF-κB activation or extrinsic apoptosis. Ubiquitin remnant profiling identified receptor-interacting protein kinase 3 (RIPK3) lysines 42, 351, and 518 as novel, USP22-regulated ubiquitination sites during necroptosis. Importantly, mutation of RIPK3 K518 reduced necroptosis-associated RIPK3 ubiquitination and amplified necrosome formation and necroptotic cell death. In conclusion, we identify a novel role of USP22 in necroptosis and further elucidate the relevance of RIPK3 ubiquitination as crucial regulator of necroptotic cell death.
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