ArticleThe Journal of clinical investigation2015
Sec63 and Xbp1 regulate IRE1α activity and polycystic disease severity.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 63 citations in OpenAlex.
- PKD1 upstream open reading frames affect Polycystin-1 expression and polycystic kidney disease phenotypes.The Journal of clinical investigation · 2026Article
- In vivo base editing reduces liver cysts in autosomal dominant polycystic kidney disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Self-cleavage of the GAIN domain of adhesion G protein-coupled receptors requires multiple domain-extrinsic factors.Nature communications · 2025Article
- Physiologic mechanisms underlying polycystic kidney disease.Physiological reviews · 2025Review
- Activation of XBP1s attenuates disease severity in models of proteotoxic Charcot-Marie-Tooth type 1B.Brain : a journal of neurology · 2025Article
- Endoplasmic reticulum stress as a driver and therapeutic target for kidney disease.Nature reviews. Nephrology · 2025Review
- Endoplasmic reticulum stress in non-small cell lung cancer.American journal of cancer research · 2025Review
- Endoplasmic reticulum stress-mediated apoptosis and autophagy in osteoarthritis: From molecular mechanisms to therapeutic applications.Cell stress & chaperones · 2024Review
- Inhibition of asparagine synthetase effectively retards polycystic kidney disease progression.EMBO molecular medicine · 2024Article
- LncRNA WFDC21P interacts with SEC63 to promote gastric cancer malignant behaviors by regulating calcium homeostasis signaling pathway.Cancer cell international · 2024Article
- Activation of XBP1s attenuates disease severity in models of proteotoxic Charcot-Marie-Tooth type 1B.bioRxiv : the preprint server for biology · 2024Article
- Research progress on endoplasmic reticulum homeostasis in kidney diseases.Cell death & disease · 2023Review
- ER Stress, the Unfolded Protein Response and Osteoclastogenesis: A Review.Biomolecules · 2023Review
- Calcium signaling in polycystic kidney disease- cell death and survival.Cell calcium · 2023Review
- Signal sequences encode information for protein folding in the endoplasmic reticulum.The Journal of cell biology · 2023Article
- Emerging links between endoplasmic reticulum stress responses and acute kidney injury.American journal of physiology. Cell physiology · 2022Review
- The down-regulation of XBP1, an unfolded protein response effector, promotes acute kidney injury to chronic kidney disease transition.Journal of biomedical science · 2022Article
- Is Nucleoredoxin a Master Regulator of Cellular Redox Homeostasis? Its Implication in Different Pathologies.Antioxidants (Basel, Switzerland) · 2022Review
- The molecular chaperone GRP170 protects against ER stress and acute kidney injury in mice.JCI insight · 2022Article
- The GPCR properties of polycystin-1- A new paradigm.Frontiers in molecular biosciences · 2022Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The HSP40 cochaperone SEC63 is associated with the SEC61 translocon complex in the ER. Mutations in the gene encoding SEC63 cause polycystic liver disease in humans; however, it is not clear how altered SEC63 influences disease manifestations. In mice, loss of SEC63 induces cyst formation both in liver and kidney as the result of reduced polycystin-1 (PC1). Here we report that inactivation of SEC63 induces an unfolded protein response (UPR) pathway that is protective against cyst formation. Specifically, using murine genetic models, we determined that SEC63 deficiency selectively activates the IRE1α-XBP1 branch of UPR and that SEC63 exists in a complex with PC1. Concomitant inactivation of both SEC63 and XBP1 exacerbated the polycystic kidney phenotype in mice by markedly suppressing cleavage at the G protein-coupled receptor proteolysis site (GPS) in PC1. Enforced expression of spliced XBP1 (XBP1s) enhanced GPS cleavage of PC1 in SEC63-deficient cells, and XBP1 overexpression in vivo ameliorated cystic disease in a murine model with reduced PC1 function that is unrelated to SEC63 inactivation. Collectively, the findings show that SEC63 function regulates IRE1α/XBP1 activation, SEC63 and XBP1 are required for GPS cleavage and maturation of PC1, and activation of XBP1 can protect against polycystic disease in the setting of impaired biogenesis of PC1.
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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.