ArticleThe Journal of biological chemistry2012
Control of type I interferon-induced cell death by Orai1-mediated calcium entry in T cells.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Is the SPLUNC1-Orai1 axis a critical determinant of lung health?Biochemical Society transactions · 2025Review
- ORAI1 Limits SARS-CoV-2 Infection by Regulating Tonic Type I IFN Signaling.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Article
- SOCE in the cardiomyocyte: the secret is in the chambers.Pflugers Archiv : European journal of physiology · 2021Review
- Calcium Ions Aggravate Alzheimer's Disease Through the Aberrant Activation of Neuronal Networks, Leading to Synaptic and Cognitive Deficits.Frontiers in molecular neuroscience · 2021Review
- Targeted Stat2 deletion in conventional dendritic cells impairs CTL responses but does not affect antibody production.Oncoimmunology · 2020Article
- Article
- Host STAT2/type I interferon axis controls tumor growth.International journal of cancer · 2015Article
- Influence of external calcium and thapsigargin on the uptake of polystyrene beads by the macrophage-like cell lines U937 and MH-S.BMC pharmacology & toxicology · 2014Article
- Anti-tumour activity and store operated calcium entry: new roles in immunology.EMBO molecular medicine · 2013Article
- Interferons as inducers of apoptosis in malignant cells.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2013Review
- Orai1-NFAT signalling pathway triggered by T cell receptor stimulation.Molecules and cells · 2013Review
- STIM proteins: dynamic calcium signal transducers.Nature reviews. Molecular cell biology · 2012Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Store-operated Ca(2+) entry (SOCE) is an essential process in T cell activation. SOCE is controlled by the Ca(2+) release-activated Ca(2+) (CRAC) channel encoded by the gene Orai1 that is expressed on the plasma membrane and activated by STIM1 when ER Ca(2+) stores are depleted. Our earlier work showed that a somatic T-cell line Jurkat mutant H123 bearing a defect in Ca(2+) signaling was susceptible to the apoptotic effects of type I interferons (IFN-α/β). The nature of the mutation and whether this mutation was linked to IFN-α/β apoptotic susceptibility was unknown. Here we show that H123 cells lacked Orai1 and exhibit reduced STIM1 protein. Reconstitution of both Orai1 and STIM1 in H123 cells rescued SOCE in response to thapsigargin and ionomycin and abrogated IFN-α/β-induced apoptosis. Reciprocally, overexpression of the dominant negative Orai1-E106A in either parental Jurkat cells or an unrelated human T cell line (CEM391) inhibited SOCE and led to sensitization to IFN-α/β-induced apoptosis. Furthermore, we showed that the Ca(2+) response pathway antagonized the IFN-α/β -induced transcriptional responses; in the absence of SOCE, this negative regulatory effect was lost. However, the inhibitory effect of Ca(2+) on type I IFN-induced gene transcription was diminished by pharmacological inhibition of NF-κB in cells with intact SOCE. Our findings reveal an unexpected and novel regulatory crosstalk mechanism between type I IFNs and store-operated Ca(2+) signaling pathways mediated at least in part by NF-κB activity with significant clinical implications to both viral and tumor immunology.
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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.