ArticleNature structural & molecular biology2017
CNPY2 is a key initiator of the PERK-CHOP pathway of the unfolded protein response.
Article in Nature structural & molecular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Epigenome-wide meta-analysis of PTSD symptom severity in three military cohorts implicates DNA methylation changes in genes involved in immune system and oxidative stress.Molecular psychiatry · 2022Pooled it
- Cnpy1 is a candidate endoplasmic reticulum chaperone of vomeronasal type 2 GPCRs.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Multifaceted role of CNPY2 beyond ER stress: Disease implications and therapeutic potential.Cell stress · 2026Article
- LncRNA ZFAS1 Combined with SRSF1 Regulate CNPY2 Expression and Leads to Microglia Endoplasmic Reticulum Stress-Induced Spinal Cord Injury.Molecular neurobiology · 2025Article
- Therapeutic effects of adipose tissue-derived mesenchymal stem cells on ER stress in a murine model of metabolic dysfunction-associated steatohepatitis: an in vivo and in vitro study.Stem cell research & therapy · 2025Article
- CNPY2 Aggravates Renal Tubular Cell Ferroptosis in Diabetic Nephropathy by Regulating PERK/ATF4/CHAC1 Pathway and MAM Integrity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Pathogenesis and Therapeutic Perspectives of Tubular Injury in Diabetic Kidney Disease: An Update.Biomedicines · 2025Review
- CNPY2 drives DSS-induced colitis via the macrophage-ROS axis.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- Testing Protein Stress Signals in Peripheral Immunocytes Under the Same Treatment Capable of Decreasing the Incidence of Alzheimer's Disease in Bladder Cancer Patients.Current issues in molecular biology · 2025Article
- Inhalable Hsa-miR-30a-3p Liposomes Attenuate Pulmonary Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A novel TLR4 accessory molecule drives hepatic oncogenesis through tumor-associated macrophages.Cancer letters · 2025Article
- Review
- The role of canopy family proteins: biological mechanism and disease function.Molecular biology reports · 2025Review
- The impact of aerobic and anaerobic exercise interventions on the management and outcomes of non-alcoholic fatty liver disease.Physiological research · 2024Review
- Skeletal Muscle SIRT3 Deficiency Contributes to Pulmonary Vascular Remodeling in Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction.Circulation · 2024Article
- Deficiency of ASGR1 promotes liver injury by increasing GP73-mediated hepatic endoplasmic reticulum stress.Nature communications · 2024Article
- Linear motifs regulating protein secretion, sorting and autophagy in Leishmania parasites are diverged with respect to their host equivalents.PLoS computational biology · 2024Article
- CNPY2 protects against ER stress and is expressed by corticostriatal neurons together with CTIP2 in a mouse model of Huntington's disease.Frontiers in molecular neuroscience · 2024Article
- Review
- The Role of Endoplasmic Reticulum Stress Response in Liver Regeneration.Seminars in liver disease · 2023Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 2 countries.
Funding
Abstract
The unfolded protein response (UPR) in the endoplasmic reticulum (ER) is a highly conserved protein-quality-control mechanism critical for cells to make survival-or-death decisions under ER-stress conditions. However, how UPR sensors are activated remains unclear. Here, we report that ER luminal protein canopy homolog 2 (CNPY2) is released from grp78 upon ER stress. Free CNPY2 then engages protein kinase R-like ER kinase (PERK) to induce expression of the transcription factor C/EBP homologous protein (CHOP), thereby initiating the UPR. Indeed, deletion of CNPY2 blocked the PERK-CHOP pathway and protected mice from UPR-induced liver damage and steatosis. Additionally, CNPY2 is transcriptionally upregulated by CHOP in a forward-feed loop to further enhance UPR signaling. These findings demonstrate the critical roles of CNPY2 in ER stress and suggest that CNPY2 is a potential new therapeutic target for UPR-related diseases such as metabolic disorders, inflammation and cancer.
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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.