ArticleThe Biochemical journal2012
Isoform-selective induction of human p110δ PI3K expression by TNFα: identification of a new and inducible PIK3CD promoter.
Article in The Biochemical journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 50 citations in OpenAlex.
- The conformation-selective PI3Kδ inhibitor roginolisib in patients with advanced or metastatic cancer, including metastatic uveal melanoma: first-in-human clinical trial.Nature communications · 2026Article
- Nitroxidative Stress, Cell-Signaling Pathways, and Manganese Porphyrins: Therapeutic Potential in Neuropathic Pain.International journal of molecular sciences · 2025Review
- Redefinition of Synovial Fibroblasts in Rheumatoid Arthritis.Aging and disease · 2024Review
- Shear stress and pathophysiological PI3K involvement in vascular malformations.The Journal of clinical investigation · 2024Review
- Disruption of DLL4/NOTCH1 Causes Dysregulated PPARγ/AKT Signaling in Pulmonary Arterial Hypertension.bioRxiv : the preprint server for biology · 2024Article
- PI3Kδ Pathway Dysregulation and Unique Features of Its Inhibition by Leniolisib in Activated PI3Kδ Syndrome and Beyond.The journal of allergy and clinical immunology. In practice · 2024Article
- Review
- Article
- Aberrant PI3Kδ splice isoform as a potential biomarker and novel therapeutic target for endocrine cancers.Frontiers in endocrinology · 2023Article
- Network analysis of synovial RNA sequencing identifies gene-gene interactions predictive of response in rheumatoid arthritis.Arthritis research & therapy · 2022Article
- Article
- PI3K inhibitors are finally coming of age.Nature reviews. Drug discovery · 2021Review
- Combinatorial treatment with Gefitinib and Bay11-7085 sensitizes primary Gefitinib-resistant OSCC cells by influencing the EGFR- NFκB signaling axis.Medical oncology (Northwood, London, England) · 2021Article
- Recent Updates on the Involvement of PI3K/AKT/mTOR Molecular Cascade in the Pathogenesis of Hyperproliferative Skin Disorders.Frontiers in medicine · 2021Review
- Lower peripheral helper T cell levels in the synovium are associated with a better response to anti-TNF therapy in rheumatoid arthritis.Arthritis research & therapy · 2020Article
- PIK3Cδ expression by fibroblasts promotes triple-negative breast cancer progression.The Journal of clinical investigation · 2020Article
- Article
- Microglia Mediated Neuroinflammation: Focus on PI3K Modulation.Biomolecules · 2020Review
- Inhibition of PI3Kδ Enhances Poly I:C-Induced Antiviral Responses and Inhibits Replication of Human Metapneumovirus in Murine Lungs and Human Bronchial Epithelial Cells.Frontiers in immunology · 2020Article
- Transcription of PIK3CD in human brain and schizophrenia: regulation by proinflammatory cytokines.Human molecular genetics · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
PI3Ks (phosphoinositide 3-kinases) are signalling molecules and drug targets with important biological functions, yet the regulation of PI3K gene expression is poorly understood. Key PI3Ks are the class IA PI3Ks that consist of a catalytic subunit (p110α, p110β and p110δ) in complex with a p85 regulatory subunit. Whereas p110α and p110β are ubiquitously expressed, high levels of p110δ are mainly found in white blood cells, with most non-leucocytes expressing low levels of p110δ. In the present paper we report that TNFα (tumour necrosis factor α) stimulation induces p110δ expression in human ECs (endothelial cells) and synovial fibroblasts, but not in leucocytes, through transcription start sites located in a novel promoter region in the p110δ gene (PIK3CD). This promoter is used in all cell types, including solid tumour cell lines that express p110δ, and is activated by TNFα in ECs and synovial fibroblasts. We further present a detailed biochemical and bioinformatic characterization of p110δ gene regulation, demonstrating that PIK3CD has distinct promoters, some of which can be dynamically activated by pro-inflammatory mediators. This is the first molecular identification of a PI3K promoter under the control of acute extracellular stimulation.
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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.