ArticleNature medicine2010
The regulatory subunits of PI3K, p85alpha and p85beta, interact with XBP-1 and increase its nuclear translocation.
Article in Nature medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 171 papers.
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Who cites it
171 citing papers in PubMed, 279 citations in OpenAlex.
- Skeletal Muscle and Circulating microRNAs Adaptations to 12-Week HIIT With or Without L-Citrulline in Obese Older Adults.Journal of cachexia, sarcopenia and muscle · 2026Trial
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- The unfolded protein response and its activation by insulin in muscle are not altered by obesity or type 2 diabetes.Clinical science (London, England : 1979) · 2026Article
- Phase separation of p85β modulates hepatocellular carcinoma progression through POLR1A.International journal of biological sciences · 2026Article
- Family with sequence similarity 114 member A1 orchestrates immune evasion in triple-negative breast cancer.Signal transduction and targeted therapy · 2025Article
- PMAIP1 mediates endoplasmic reticulum stress in human dental pulp stem cells during pulpitis pathogenesis.BMC oral health · 2025Article
- Curcumin ameliorates heatstroke-induced lung injury by activating the PI3K/AKT pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Identifying Specificity Protein 2 as a key marker for diabetic encephalopathy in the context of predictive, preventive, and personalized medicine.The EPMA journal · 2025Article
- p85β acts as a transcription cofactor and cooperates with BCLAF1 in the nucleus.Nature communications · 2025Article
- Non-catalytic role of phosphoinositide 3-kinase in mesenchymal cell migration through non-canonical induction of p85β/AP2-mediated endocytosis.Nature communications · 2024Article
- Exploring mechanisms underlying diabetes comorbidities and strategies to prevent vascular complications.Diabetology international · 2024Review
- Application and mechanism of Chinese herb medicine in the treatment of non-alcoholic fatty liver disease.Frontiers in pharmacology · 2024Review
- ER stress and unfolded protein response (UPR) signaling modulate GLP-1 receptor signaling in the pancreatic islets.Molecules and cells · 2024Article
- The activation of spliced X-box binding protein 1 by isorhynchophylline therapy improves diabetic encephalopathy.Cell biology and toxicology · 2023Article
- BRD7 improves glucose homeostasis independent of IRS proteins.The Journal of endocrinology · 2023Article
- The Role of PIK3R1 in Metabolic Function and Insulin Sensitivity.International journal of molecular sciences · 2023Review
- Fructose induced KHK-C can increase ER stress independent of its effect on lipogenesis to drive liver disease in diet-induced and genetic models of NAFLD.Metabolism: clinical and experimental · 2023Article
- PIK3CA mutation in endometriotic epithelial cells promotes viperin-dependent inflammatory response to insulin.Reproductive biology and endocrinology : RB&E · 2023Article
- X-box Binding Protein 1: An Adaptor in the Pathogenesis of Atherosclerosis.Aging and disease · 2023Review
- Genome-wide copy number variation detection in a large cohort of diverse horse breeds by whole-genome sequencing.Frontiers in veterinary science · 2023Article
111 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Despite the fact that X-box binding protein-1 (XBP-1) is one of the main regulators of the unfolded protein response (UPR), the modulators of XBP-1 are poorly understood. Here, we show that the regulatory subunits of phosphotidyl inositol 3-kinase (PI3K), p85alpha (encoded by Pik3r1) and p85beta (encoded by Pik3r2) form heterodimers that are disrupted by insulin treatment. This disruption of heterodimerization allows the resulting monomers of p85 to interact with, and increase the nuclear translocation of, the spliced form of XBP-1 (XBP-1s). The interaction between p85 and XBP-1s is lost in ob/ob mice, resulting in a severe defect in XBP-1s translocation to the nucleus and thus in the resolution of endoplasmic reticulum (ER) stress. These defects are ameliorated when p85alpha and p85beta are overexpressed in the liver of ob/ob mice. Our results define a previously unknown insulin receptor signaling pathway and provide new mechanistic insight into the development of ER stress during obesity.
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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.