ArticleThe Journal of biological chemistry2016
Transcriptional Regulation of X-Box-binding Protein One (XBP1) by Hepatocyte Nuclear Factor 4α (HNF4Α) Is Vital to Beta-cell Function.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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
20 citing papers in PubMed, 29 citations in OpenAlex.
- Maturity Onset Diabetes of the Young (MODY): French National Diagnosis and Care Protocol (PNDS, Protocole National de Diagnostic et de Soins).Orphanet journal of rare diseases · 2026Review
- Article
- Characterizing the Ovarian Cytogenetic Dynamics of Sichuan Bream (International journal of molecular sciences · 2025Article
- Roles of X-box binding protein 1 in liver pathogenesis.Clinical and molecular hepatology · 2025Review
- TANGO1 Dances to Export of Procollagen from the Endoplasmic Reticulum.Fibrosis (Hong Kong, China) · 2023Article
- SOX9 Governs Gastric Mucous Neck Cell Identity and Is Required for Injury-Induced Metaplasia.Cellular and molecular gastroenterology and hepatology · 2023Article
- Cell plasticity in regeneration in the stomach and beyond.Current opinion in genetics & development · 2022Review
- XBP1 maintains beta cell identity, represses beta-to-alpha cell transdifferentiation and protects against diabetic beta cell failure during metabolic stress in mice.Diabetologia · 2022Article
- Living Dangerously: Protective and Harmful ER Stress Responses in Pancreatic β-Cells.Diabetes · 2021Review
- Roles of XBP1s in Transcriptional Regulation of Target Genes.Biomedicines · 2021Review
- Intersection of the ATF6 and XBP1 ER stress pathways in mouse islet cells.The Journal of biological chemistry · 2020Article
- Is the secret of VDAC Isoforms in their gene regulation? Characterization of humanInternational journal of molecular sciences · 2020Article
- Review
- HNF4a transcription is a target of trichloroethylene toxicity in the embryonic mouse heart.Environmental science. Processes & impacts · 2020Article
- Proliferation and Differentiation of Gastric Mucous Neck and Chief Cells During Homeostasis and Injury-induced Metaplasia.Gastroenterology · 2020Article
- Role of hepatocyte nuclear factor 4-alpha in gastrointestinal and liver diseases.World journal of gastroenterology · 2019Review
- The role of lineage specifiers in pancreatic ductal adenocarcinoma.Journal of gastrointestinal oncology · 2018Review
- Trichloroethylene perturbs HNF4a expression and activity in the developing chick heart.Toxicology letters · 2018Article
- Patterning the gastrointestinal epithelium to confer regional-specific functions.Developmental biology · 2018Review
- Hepatocyte nuclear factor 4α is required for cell differentiation and homeostasis in the adult mouse gastric epithelium.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
The transcription factor, X-box-binding protein-1 (XBP1), controls the development and maintenance of the endoplasmic reticulum (ER) in multiple secretory cell lineages. We show here that Hepatocyte Nuclear Factor 4α (HNF4α) directly induces XBP1 expression. Mutations in HNF4α cause Mature-Onset Diabetes of the Young I (MODYI), a subset of diabetes characterized by diminished GSIS. In mouse models, cell lines, and ex vivo islets, using dominant negative and human- disease-allele point mutants or knock-out and knockdown models, we show that disruption of HNF4α caused decreased expression of XBP1 and reduced cellular ER networks. GSIS depends on ER Ca(2+) signaling; we show that diminished XBP1 and/or HNF4α in β-cells led to impaired ER Ca(2+) homeostasis. Restoring XBP1 expression was sufficient to completely rescue GSIS in HNF4α-deficient β-cells. Our findings uncover a transcriptional relationship between HNF4α and Xbp1 with potentially broader implications about MODYI and the importance of transcription factor signaling in the regulation of secretion.
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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.