ArticleMolecular and cellular biology2003
Transcriptional program of apoptosis induction following interleukin 2 deprivation: identification of RC3, a calcium/calmodulin binding protein, as a novel proapoptotic factor.
Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 37 citations in OpenAlex.
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- Surgical necrotizing enterocolitis in extremely premature neonates is associated with genetic variations in an intergenic region of chromosome 8.Pediatric research · 2018Article
- Ethnicity-specific epigenetic variation in naïve CD4+ T cells and the susceptibility to autoimmunity.Epigenetics & chromatin · 2015Article
- A functional interplay between 5-lipoxygenase and μ-calpain affects survival and cytokine profile of human Jurkat T lymphocyte exposed to simulated microgravity.BioMed research international · 2014Article
- MiR-17-92 cluster: an apoptosis inducer or proliferation enhancer.Molecular and cellular biochemistry · 2013Article
- The calmodulin regulator protein, PEP-19, sensitizes ATP-induced Ca2+ release.The Journal of biological chemistry · 2013Article
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- Tanshinone IIA activates calcium-dependent apoptosis signaling pathway in human hepatoma cells.Journal of natural medicines · 2012Article
- Induction of PP2A Bβ, a regulator of IL-2 deprivation-induced T-cell apoptosis, is deficient in systemic lupus erythematosus.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Preferential enhancement of older human T cell cytokine generation, chemotaxis, proliferation and survival by lenalidomide.Clinical immunology (Orlando, Fla.) · 2011Article
- Apoptosis of CD4+ CD25(high) T cells in type 1 diabetes may be partially mediated by IL-2 deprivation.PloS one · 2009Article
- Article
- Molecular signature of cell cycle exit induced in human T lymphoblasts by IL-2 withdrawal.BMC genomics · 2009Article
- Charting calcium-regulated apoptosis pathways using chemical biology: role of calmodulin kinase II.BMC chemical biology · 2008Article
- Proteomics analysis of the expression of neurogranin in murine neuroblastoma (Neuro-2a) cells reveals its involvement for cell differentiation.International journal of biological sciences · 2007Article
- Characterization of transcriptional regulation of neurogranin by nitric oxide and the role of neurogranin in SNP-induced cell death: implication of neurogranin in an increased neuronal susceptibility to oxidative stress.International journal of biological sciences · 2007Article
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Apoptosis of mature T lymphocytes preserves immune system homeostasis by counteracting transient increases in T-cell number. This process is regulated, at least in part, by the cytokine interleukin 2 (IL-2): T cells deprived of IL-2 undergo apoptosis. The mechanism of apoptosis induction by IL-2 deprivation remains to be determined but is known to require RNA synthesis, implying the existence of transcriptionally activated genes whose products induce cell death. To identify such genes, we have performed expression profiling in IL-2-dependent T cells following cytokine deprivation. Our results reveal an intricate transcriptional program entailing the induction of known proapoptotic factors and the simultaneous repression of known antiapoptotic factors. Surprisingly, one gene whose transcription substantially increased was RC3 (also called neurogranin), which encodes a calmodulin binding protein thought to be a neural-specific factor involved in learning and memory. We show that ectopic expression of RC3 in IL-2-dependent T cells increases the intracellular Ca(2+) concentration and induces apoptosis even in the presence of cytokine. Buffering the Ca(2+) increase with the cytoplasmic Ca(2+) chelator BAPTA-AM [1,2-bis(2-aminophenoxy)ethane-N,N,N1,N-tetraacetic acid] blocks RC3-induced apoptosis, indicating that the rise in intracellular Ca(2+) is required for apoptotic death. RC3 mutants unable to bind calmodulin fail to increase intracellular Ca(2+) levels and to induce apoptosis. Based upon these results, we propose that IL-2 deprivation raises the level of RC3 and other apoptotic factors, which induce apoptosis by increasing the intracellular Ca(2+) concentration.
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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.