ArticleNature communications2021
ARIH1 signaling promotes anti-tumor immunity by targeting PD-L1 for proteasomal degradation.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 111 citations in OpenAlex.
- Post‑translational modification‑governed immune states in cancer immunity: Biomarker implications for checkpoint competence, tumor visibility and immunotherapy resistance (Review).International journal of oncology · 2026Review
- ClonalLife science alliance · 2026Article
- Proximal Proteomics Reveals Potential Regulators of Programmed Death-Ligand 1 in Human Cancer.ACS omega · 2026Article
- Repurposed ethoxzolamide reprograms antitumor immunity through β-TrCP-dependent PD-L1 ubiquitination.Cell reports. Medicine · 2026Article
- Decoding the crosstalk between ubiquitination and other post-translational modifications in cancer immunity: from mechanisms to clinical prospects.NPJ precision oncology · 2026Review
- ROCK1 inhibition primes anti-tumor immunity in EGFR-mutant NSCLC by triggering PD-L1 degradation mediated by SMURF2.Molecular cancer · 2026Article
- Ubenimex synergizes with the PD-L1 blockade in gastric cancer by competitively binding LAP3 with UBE3A.Cell death & disease · 2026Article
- Proanthocyanidins enhance antitumor immunity by promoting ubiquitin-proteasomal PD-L1 degradation via stabilization of LKB1 and SYVN1.The Journal of clinical investigation · 2026Article
- Sec61β maintains cytoplasmic proteostasis via ARIH1-mediated translational repression upon ER stress.EMBO reports · 2026Article
- Paroxetine repurposing enhances antitumor immunity via SPOP-mediated PD-L1 ubiquitination and proteasomal degradation.Journal of experimental & clinical cancer research : CR · 2026Article
- Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications.Journal of biomedical science · 2026Review
- The lipid-metabolic enzyme HSD17B12 drives lysosomal degradation of PD-L1 potentiating anti-tumor immunity in a mouse model.PLoS biology · 2026Article
- O-GlcNAcylation stabilizes RSK4 by antagonizing GSK3β-mediated phosphorylation to enhance radioresistance in esophageal squamous cell carcinoma.International journal of biological sciences · 2026Article
- Intracellular PD-L1: Functions, Regulation, and Therapeutic Implications.International journal of biological sciences · 2026Review
- Statins attenuate PD-L1 sorting to small extracellular vesicles dependent on ubiquitin-like 3 modification.Scientific reports · 2025Article
- Black phosphorus nanosheets boost mitochondrial oxidative phosphorylation improving immunotherapy outcomes.Nature nanotechnology · 2025Article
- Pyrotinib inhibits the tumorigenicity of HER2-positive non-small cell lung cancer by inducing ARIH1/ubiquitin/lysosome-dependent degradation of HER2.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Suppression of tumor growth by GMI, an edible fungal immunomodulatory protein, is associated with targeting GSK3β‑mediated proteasomal degradation of PD‑L1.International journal of molecular medicine · 2025Article
- Molecular mechanisms and potential targeting strategies of ubiquitin‑proteasome system‑mediated PD‑1/PD‑L1 ubiquitination in tumor immune suppression (Review).Oncology reports · 2025Review
- LSD1 inhibition sensitizes anti-PD1 blockade immunotherapy by inhibiting the long-range attack of tumor-derived extracellular vesicles.Acta pharmaceutica Sinica. B · 2025Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
24 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer expression of PD-L1 suppresses anti-tumor immunity. PD-L1 has emerged as a remarkable therapeutic target. However, the regulation of PD-L1 degradation is not understood. Here, we identify several compounds as inducers of PD-L1 degradation using a high-throughput drug screen. We find EGFR inhibitors promote PD-L1 ubiquitination and proteasomal degradation following GSK3α-mediated phosphorylation of Ser279/Ser283. We identify ARIH1 as the E3 ubiquitin ligase responsible for targeting PD-L1 to degradation. Overexpression of ARIH1 suppresses tumor growth and promotes cytotoxic T cell activation in wild-type, but not in immunocompromised mice, highlighting the role of ARIH1 in anti-tumor immunity. Moreover, combining EGFR inhibitor ES-072 with anti-CTLA4 immunotherapy results in an additive effect on both tumor growth and cytotoxic T cell activation. Our results delineate a mechanism of PD-L1 degradation and cancer escape from immunity via EGFR-GSK3α-ARIH1 signaling and suggest GSK3α and ARIH1 might be potential drug targets to boost anti-tumor immunity and enhance immunotherapies.
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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.