ArticleNature medicine2010
A regulatory subunit of phosphoinositide 3-kinase increases the nuclear accumulation of X-box-binding protein-1 to modulate the unfolded protein response.
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 123 papers.
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Who cites it
123 citing papers in PubMed, 190 citations in OpenAlex.
- 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
- Article
- Phase separation of p85β modulates hepatocellular carcinoma progression through POLR1A.International journal of biological sciences · 2026Article
- A single-cell transcriptomic landscape characterizes the endocrine system aging in the mouse.Protein & cell · 2026Article
- Pre-established ATF4 occupancy and chromatin organization instruct selective transcription activation during integrated stress response.Nature communications · 2025Article
- Polymerized laminin-modified microcapsules improve pancreatic islet resilience towards cytokine induced inflammatory stress and lower chemoattractant cytokine secretion.Materials today. Bio · 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
- A novel gene signature based on endoplasmic reticulum stress for predicting prognosis in hepatocellular carcinoma.Translational cancer research · 2024Article
- 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
- The activation of spliced X-box binding protein 1 by isorhynchophylline therapy improves diabetic encephalopathy.Cell biology and toxicology · 2023Article
- Genes That Extend Lifespan May Do So by Mitigating the Increased Risk of Death Posed by Having Hypertension.American journal of hypertension · 2023Article
- The Role of PIK3R1 in Metabolic Function and Insulin Sensitivity.International journal of molecular sciences · 2023Review
- Change Profiles and Functional Targets of MicroRNAs in Type 2 Diabetes Mellitus Patients with Obesity.Diabetes & metabolism journal · 2023Article
- Comparative Analysis of Active Ingredients and Potential Bioactivities of Essential Oils fromMolecules (Basel, Switzerland) · 2023Article
- Fatty Liver Disease, Metabolism and Alcohol Interplay: A Comprehensive Review.International journal of molecular sciences · 2023Review
- Dysregulated UPR and ER Stress Related to a Mutation in theInternational journal of molecular sciences · 2023Article
- Divergent roles of the regulatory subunits of class IA PI3K.Frontiers in endocrinology · 2023Review
63 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Class Ia phosphoinositide 3-kinase (PI3K), an essential mediator of the metabolic actions of insulin, is composed of a catalytic (p110alpha or p110beta) and regulatory (p85alphaalpha, p85betaalpha or p55alpha) subunit. Here we show that p85alphaalpha interacts with X-box-binding protein-1 (XBP-1), a transcriptional mediator of the unfolded protein response (UPR), in an endoplasmic reticulum (ER) stress-dependent manner. Cell lines with knockout or knockdown of p85alphaalpha show marked alterations in the UPR, including reduced ER stress-dependent accumulation of nuclear XBP-1, decreased induction of UPR target genes and increased rates of apoptosis. This is associated with a decreased activation of inositol-requiring protein-1alpha (IRE1alpha) and activating transcription factor-6alphaalpha (ATF6alpha). Mice with deletion of p85alpha in liver (L-Pik3r1(-/-)) show a similar attenuated UPR after tunicamycin administration, leading to an increased inflammatory response. Thus, p85alphaalpha forms a previously unrecognized link between the PI3K pathway, which is central to insulin action, and the regulation of the cellular response to ER stress, a state that when unresolved leads to insulin resistance.
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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.