ArticleThe Journal of biological chemistry2015
Cystatin D locates in the nucleus at sites of active transcription and modulates gene and protein expression.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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Who cites it
19 citing papers in PubMed, 35 citations in OpenAlex.
- Causal relationship between oral microbiome, circulating inflammatory proteins and lung cancer: A Mendelian randomization study.Medicine · 2026Article
- Combining Mendelian randomization and multiomics data to determine the causal relationship between systemic inflammation and head and neck squamous cell carcinoma.Cancer cell international · 2026Article
- Causality relationship between 91 inflammatory factors and Alzheimer disease: A bidirectional Mendelian randomization study.Medicine · 2026Article
- Evaluation of the relationship between inflammation and typical chest pain in ST-elevation myocardial infarction.Clinical proteomics · 2026Article
- Exploring upstream and downstream causality of inflammatory cytokines in intervertebral disc degeneration: a bidirectional, two-sample Mendelian randomization study.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2025Article
- Cystatin D as a biomarker for rheumatoid arthritis: relation to disease activity and joint damage.Reumatologia · 2025Article
- Causal Relationships Between Circulating Inflammatory Proteins and Obstructive Sleep Apnea: A Bidirectional Mendelian Randomization Study.Nature and science of sleep · 2024Article
- Salivary Cystatin D Interactome in Patients with Systemic Mastocytosis: An Exploratory Study.International journal of molecular sciences · 2023Article
- Association of extracellular vesicle inflammatory proteins and mortality.Scientific reports · 2022Article
- Cathepsins and Their Endogenous Inhibitors in Host Defense DuringFrontiers in immunology · 2021Review
- Modulation of Cystatin C in Human Macrophages Improves Anti-Mycobacterial Immune Responses toFrontiers in immunology · 2021Article
- Review
- Depression, GABA, and Age Correlate with Plasma Levels of Inflammatory Markers.International journal of molecular sciences · 2019Article
- Up-regulated CST5 inhibits bone resorption and activation of osteoclasts in rat models of osteoporosis via suppression of the NF-κB pathway.Journal of cellular and molecular medicine · 2019Article
- Cysteine Cathepsin Protease Inhibition: An update on its Diagnostic, Prognostic and Therapeutic Potential in Cancer.Pharmaceuticals (Basel, Switzerland) · 2019Review
- Journey of cystatins from being mere thiol protease inhibitors to at heart of many pathological conditions.International journal of biological macromolecules · 2017Review
- Cystatin D (CST5): An ultra-early inflammatory biomarker of traumatic brain injury.Scientific reports · 2017Article
- Vitamin D and the Epithelial to Mesenchymal Transition.Stem cells international · 2016Review
- Innate Immune Response in Brain, NF-Kappa B Signaling and Cystatins.Frontiers in molecular neuroscience · 2015Review
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cystatin D is an inhibitor of lysosomal and secreted cysteine proteases. Strikingly, cystatin D has been found to inhibit proliferation, migration, and invasion of colon carcinoma cells indicating tumor suppressor activity that is unrelated to protease inhibition. Here, we demonstrate that a proportion of cystatin D locates within the cell nucleus at specific transcriptionally active chromatin sites. Consistently, transcriptomic analysis show that cystatin D alters gene expression, including that of genes encoding transcription factors such as RUNX1, RUNX2, and MEF2C in HCT116 cells. In concordance with transcriptomic data, quantitative proteomic analysis identified 292 proteins differentially expressed in cystatin D-expressing cells involved in cell adhesion, cytoskeleton, and RNA synthesis and processing. Furthermore, using cytokine arrays we found that cystatin D reduces the secretion of several protumor cytokines such as fibroblast growth factor-4, CX3CL1/fractalkine, neurotrophin 4 oncostatin-M, pulmonary and activation-regulated chemokine/CCL18, and transforming growth factor B3. These results support an unanticipated role of cystatin D in the cell nucleus, controlling the transcription of specific genes involved in crucial cellular functions, which may mediate its protective action in colon cancer.
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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.