ArticleMolecular metabolism2015
Clic4, a novel protein that sensitizes β-cells to apoptosis.
Article in Molecular metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Genetic alterations in coronary cell lines exposed to sirolimus and paclitaxel.Archives of toxicology · 2025Article
- The role of chloride intracellular channel 4 in tumors.Cancer cell international · 2025Review
- Bcl-2 and Bcl-xL in Diabetes: Contributions to Endocrine Pancreas Viability and Function.Biomedicines · 2025Review
- Retrograde AAV-mediated gene modulation reveals chloride intracellular channel proteins as potent regulators of retinal ganglion cell death.Experimental neurology · 2024Article
- Hidden Glutathione Transferases in the Human Genome.Biomolecules · 2023Article
- Structure-based discovery and in vitro validation of inhibitors of chloride intracellular channel 4 protein.Computational and structural biotechnology journal · 2023Article
- Mitochondrial ion channels in pancreatic β-cells: Novel pharmacological targets for the treatment of Type 2 diabetes.British journal of pharmacology · 2021Review
- The Hepatic Microenvironment Uniquely Protects Leukemia Cells through Induction of Growth and Survival Pathways Mediated by LIPG.Cancer discovery · 2021Article
- Anti-tumor activities of the new oral pan-RAF inhibitor, TAK-580, used as monotherapy or in combination with novel agents in multiple myeloma.Oncotarget · 2020Article
- Intracellular Chloride Channels: Novel Biomarkers in Diseases.Frontiers in physiology · 2020Review
- Cyclin-dependent kinase 5-mediated phosphorylation of chloride intracellular channel 4 promotes oxidative stress-induced neuronal death.Cell death & disease · 2018Article
- Three Decades of Chloride Intracellular Channel Proteins: From Organelle to Organ Physiology.Current protocols in pharmacology · 2018Review
- Pathological Effects of Exosomes in Mediating Diabetic Cardiomyopathy.Advances in experimental medicine and biology · 2017Review
- Cell type-specific deletion in mice reveals roles for PAS kinase in insulin and glucagon production.Diabetologia · 2016Article
- Molecular Genetic Regulation of Slc30a8/ZnT8 Reveals a Positive Association With Glucose Tolerance.Molecular endocrinology (Baltimore, Md.) · 2016Article
- Chloride intracellular channel 4 is required for maturation of the cerebral collateral circulation.American journal of physiology. Heart and circulatory physiology · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
objectivesChloride intracellular channel protein 4 (Clic4) is a ubiquitously expressed protein involved in multiple cellular processes including cell-cycle control, cell differentiation, and apoptosis. Here, we investigated the role of Clic4 in pancreatic β-cell apoptosis.
methodsWe used βTC-tet cells and islets from β-cell specific Clic4 knockout mice (βClic4KO) and assessed cytokine-induced apoptosis, Bcl2 family protein expression and stability, and identified Clic4-interacting proteins by co-immunoprecipitation and mass spectrometry analysis.
resultsWe show that cytokines increased Clic4 expression in βTC-tet cells and in mouse islets and siRNA-mediated silencing of Clic4 expression in βTC-tet cells or its genetic inactivation in islets β-cells, reduced cytokine-induced apoptosis. This was associated with increased expression of Bcl-2 and increased expression and phosphorylation of Bad. Measurement of Bcl-2 and Bad half-lives in βTC-tet cells showed that Clic4 silencing increased the stability of these proteins. In primary islets β-cells, absence of Clic4 expression increased Bcl-2 and Bcl-xL expression as well as expression and phosphorylation of Bad. Mass-spectrometry analysis of proteins co-immunoprecipitated with Clic4 from βTC-tet cells showed no association of Clic4 with Bcl-2 family proteins. However, Clic4 co-purified with proteins from the proteasome suggesting a possible role for Clic4 in regulating protein degradation.
conclusionsCollectively, our data show that Clic4 is a cytokine-induced gene that sensitizes β-cells to apoptosis by reducing the steady state levels of Bcl-2, Bad and phosphorylated Bad.
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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.