ArticleThe Journal of clinical investigation2020
Sel1L-Hrd1 ER-associated degradation maintains β cell identity via TGF-β signaling.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Cross-Study Meta-Analysis of Blood Transcriptomes in Type 2 Diabetes.International journal of molecular sciences · 2025Pooled it
- Overexpression of Synoviolin and miR-125a-5p, miR-19b-3p in peripheral blood of rheumatoid arthritis patients after treatment with conventional DMARDs and methylprednisolone.Clinical rheumatology · 2024Trial
- Emerging perspectives in proteostasis: bridging mechanisms and therapeutics for human diseases.Signal transduction and targeted therapy · 2026Review
- Proteomic analyses of human islets reveal potential markers of β cell dysfunction during prediabetes.JCI insight · 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
- Neuronal SEL1L-HRD1 ER-associated degradation is essential for motor function and survival in mice.The Journal of clinical investigation · 2026Article
- SEL1L-HRD1 ER-associated degradation facilitates prohormone convertase 2 maturation and glucagon production in islet α cells.Nature communications · 2026Article
- ER-associated degradation pathway protein SEL1L plays an evolutionarily conserved role in platelet adhesion.The Journal of clinical investigation · 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
- Limiting ER-associated degradation capacity triggers acute and chronic effects on insulin biosynthesis.The Journal of clinical investigation · 2026Article
- The role of ER-associated degradation and ER-phagy in health and disease.Signal transduction and targeted therapy · 2026Review
- Ubiquitination by HRD1 is essential for TLR3 trafficking and its innate immune signaling.Nature communications · 2025Article
- SEL1L regulates ER homeostasis in Sertoli cells but is dispensable for their function.Molecular biology of the cell · 2025Article
- Structural insights into the human HRD1 ubiquitin ligase complex.Nature communications · 2025Article
- Endoplasmic reticulum (ER) protein degradation by ER-associated degradation and ER-phagy.Trends in cell biology · 2025Review
- SEL1L-HRD1-mediated ERAD in mammals.Nature cell biology · 2025Review
- VDAC1 is a target for pharmacologically induced insulin hypersecretion in β cells.Cell reports · 2025Article
- Coordinated Role of Autophagy and ERAD in Maintaining Neuroendocrine Function by Preventing Prohormone Aggregation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
β Cell apoptosis and dedifferentiation are 2 hotly debated mechanisms underlying β cell loss in type 2 diabetes; however, the molecular drivers underlying such events remain largely unclear. Here, we performed a side-by-side comparison of mice carrying β cell-specific deletion of ER-associated degradation (ERAD) and autophagy. We reported that, while autophagy was necessary for β cell survival, the highly conserved Sel1L-Hrd1 ERAD protein complex was required for the maintenance of β cell maturation and identity. Using single-cell RNA-Seq, we demonstrated that Sel1L deficiency was not associated with β cell loss, but rather loss of β cell identity. Sel1L-Hrd1 ERAD controlled β cell identity via TGF-β signaling, in part by mediating the degradation of TGF-β receptor 1. Inhibition of TGF-β signaling in Sel1L-deficient β cells augmented the expression of β cell maturation markers and increased the total insulin content. Our data revealed distinct pathogenic effects of 2 major proteolytic pathways in β cells, providing a framework for therapies targeting distinct mechanisms of protein quality control.
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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.