ArticleNature cell biology2023
SEL1L-HRD1 endoplasmic reticulum-associated degradation controls STING-mediated innate immunity by limiting the size of the activable STING pool.
Article in Nature cell biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
65 citing papers in PubMed, 90 citations in OpenAlex.
- An endoplasmic reticulum-enriched nanogel couples ferroptotic tumor damage with macrophage reprogramming for triple-negative breast cancer immunotherapy.Bioactive materials · 2027Article
- The cGAS-STING/MITA pathway in innate antiviral immunity and beyond.Cell insight · 2026Review
- ERAD inhibitor Eeyarestatin I (EerI) suppresses duck plague virus by restoring STING-mediated antiviral immunity.Poultry science · 2026Article
- Cell autonomous inflammation in VEXAS is mediated by cGAS-STING.bioRxiv : the preprint server for biology · 2026Article
- SEL1L3 suppresses colorectal cancer cell growth and metastasis by preventing endoplasmic reticulum-associated degradation of STING.Cell death & disease · 2026Article
- Functional rescue of a disease-linked ERAD pathway mutation via alternative splicing.The EMBO journal · 2026Article
- The role of the cGAS/STING pathway in skeletal muscle regeneration: modulation of inflammation, macrophage polarization, and oxidative stress.Cellular & molecular biology letters · 2026Article
- Identification of Pinostilbene as a natural STING agonist that triggers FTH1 degradation via K48-ubiquitination to induce ferroptosis in non-small cell lung cancer.Redox biology · 2026Article
- Ginsenoside Rb1 Targets the HRD1-STING Axis to Mitigate Cholesterol-Induced VSMC Senescence.Journal of clinical laboratory analysis · 2026Article
- Emerging Mechanistic Roles of STING Signaling in Kidney Diseases.The American journal of pathology · 2026Review
- Energy-sensing molecule RORγ regulates cholesterol metabolism and immune signaling in diabetic kidney disease and aging.Nature communications · 2026Article
- Functional integrity of the SEL1L-HRD1 complex is critical for endoplasmic reticulum-associated degradation and organismal viability.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Structural basis and pathological implications of the dimeric OS9-SEL1L-HRD1 ERAD Core Complex.Nature communications · 2026Article
- Stenotrophomonas promotes gastrointestinal tumor progression via STING degradation in tumour cells and mitigated immune response.Nature communications · 2026Article
- The role of ER-associated degradation and ER-phagy in health and disease.Signal transduction and targeted therapy · 2026Review
- Tripartite motif 13 orchestrates endoplasmic reticulum-associated degradation and endoplasmic reticulum-phagy to modulate dendritic cell-mediated immune responses in sepsis.Burns & trauma · 2026Article
- The mechanosensitive channel TRPV4 inhibits pulmonary inflammation by limiting NF-κB signaling in alveolar macrophages.Science signaling · 2025Article
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- Ubiquitination by HRD1 is essential for TLR3 trafficking and its innate immune signaling.Nature communications · 2025Article
- USP18 confers protection against allergic asthma by suppressing CCL8 production in alveolar type II epithelial cells.Respiratory research · 2025Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
24 authors at 6 institutions in 2 countries.
Funding
Abstract
Stimulator of interferon genes (STING) orchestrates the production of proinflammatory cytokines in response to cytosolic double-stranded DNA; however, the pathophysiological significance and molecular mechanism underlying the folding and maturation of nascent STING protein at the endoplasmic reticulum (ER) remain unknown. Here we report that the SEL1L-HRD1 protein complex-the most conserved branch of ER-associated degradation (ERAD)-is a negative regulator of the STING innate immunity by ubiquitinating and targeting nascent STING protein for proteasomal degradation in the basal state. SEL1L or HRD1 deficiency in macrophages specifically amplifies STING signalling and immunity against viral infection and tumour growth. Mechanistically, nascent STING protein is a bona fide substrate of SEL1L-HRD1 in the basal state, uncoupled from ER stress or its sensor inositol-requiring enzyme 1α. Hence, our study not only establishes a key role of SEL1L-HRD1 ERAD in innate immunity by limiting the size of the activable STING pool, but identifies a regulatory mechanism and therapeutic approach to targeting STING.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.