ArticleProceedings of the National Academy of Sciences of the United States of America2011
Huntingtin-interacting protein 14 is a type 1 diabetes candidate protein regulating insulin secretion and beta-cell apoptosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 61 citations in OpenAlex.
- CTSH regulates β-cell function and disease progression in newly diagnosed type 1 diabetes patients.Proceedings of the National Academy of Sciences of the United States of America · 2014Trial
- Regulation of cardiomyocyte intracellular trafficking and signal transduction by protein palmitoylation.Biochemical Society transactions · 2024Article
- Immune cell-derived extracellular vesicular microRNAs induce pancreatic beta cell apoptosis.Heliyon · 2022Article
- DHHC17 Is a New Regulator of AMPK Signaling.Molecular and cellular biology · 2022Article
- Regulatory effects of protein S-acylation on insulin secretion and insulin action.Open biology · 2021Review
- Article
- Proteome-Scale Analysis of ProteinJournal of proteome research · 2021Review
- Regulatory effects of post-translational modifications on zDHHCThe Journal of biological chemistry · 2020Review
- Review
- Precision medicine - networks to the rescue.Current opinion in biotechnology · 2020Review
- Advances in Knowledge of Candidate Genes Acting at the Beta-Cell Level in the Pathogenesis of T1DM.Frontiers in endocrinology · 2020Review
- Type 1 diabetes: genes associated with disease development.Central-European journal of immunology · 2020Review
- Genome wide analysis of gene expression changes in skin from patients with type 2 diabetes.PloS one · 2020Article
- Syntaxin 4 Expression in Pancreatic β-Cells Promotes Islet Function and Protects Functional β-Cell Mass.Diabetes · 2018Article
- Profilin reduces aggregation and phase separation of huntingtin N-terminal fragments by preferentially binding to soluble monomers and oligomers.The Journal of biological chemistry · 2018Article
- On type 1 diabetes mellitus pathogenesis.Endocrine connections · 2018Review
- Type 1 diabetes genome-wide association studies: not to be lost in translation.Clinical & translational immunology · 2017Review
- DNA-Methylation and Body Composition in Preschool Children: Epigenome-Wide-Analysis in the European Childhood Obesity Project (CHOP)-Study.Scientific reports · 2017Article
- Role of S-Palmitoylation by ZDHHC13 in Mitochondrial function and Metabolism in Liver.Scientific reports · 2017Article
- Type 1 Diabetes Candidate Genes Linked to Pancreatic Islet Cell Inflammation and Beta-Cell Apoptosis.Genes · 2017Review
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type 1 diabetes (T1D) is a complex disease characterized by the loss of insulin-secreting β-cells. Although the disease has a strong genetic component, and several loci are known to increase T1D susceptibility risk, only few causal genes have currently been identified. To identify disease-causing genes in T1D, we performed an in silico "phenome-interactome analysis" on a genome-wide linkage scan dataset. This method prioritizes candidates according to their physical interactions at the protein level with other proteins involved in diabetes. A total of 11 genes were predicted to be likely disease genes in T1D, including the INS gene. An unexpected top-scoring candidate gene was huntingtin-interacting protein (HIP)-14/ZDHHC17. Immunohistochemical analysis of pancreatic sections demonstrated that HIP14 is almost exclusively expressed in insulin-positive cells in islets of Langerhans. RNAi knockdown experiments established that HIP14 is an antiapoptotic protein required for β-cell survival and glucose-stimulated insulin secretion. Proinflammatory cytokines (IL-1β and IFN-γ) that mediate β-cell dysfunction in T1D down-regulated HIP14 expression in insulin-secreting INS-1 cells and in isolated rat and human islets. Overexpression of HIP14 was associated with a decrease in IL-1β-induced NF-κB activity and protection against IL-1β-mediated apoptosis. Our study demonstrates that the current network biology approach is a valid method to identify genes of importance for T1D and may therefore embody the basis for more rational and targeted therapeutic approaches.
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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.