ArticleDiabetologia2013
Baculoviral inhibitors of apoptosis repeat containing (BIRC) proteins fine-tune TNF-induced nuclear factor κB and c-Jun N-terminal kinase signalling in mouse pancreatic beta cells.
Article in Diabetologia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
- Proximity-labeling proteomics reveals remodeled interactomes and altered localization of pathogenic SHP2 variants.EMBO reports · 2026Article
- Proximity-labeling proteomics reveals remodeled interactomes and altered localization of pathogenic SHP2 variants.bioRxiv : the preprint server for biology · 2025Article
- Mapping novel QTL and fine mapping of previously identified QTL associated with glucose tolerance using the collaborative cross mice.Mammalian genome : official journal of the International Mammalian Genome Society · 2024Article
- RELA governs a network of islet-specific metabolic genes necessary for beta cell function.Diabetologia · 2023Article
- Baculoviral inhibitor of apoptosis protein repeat-containing protein 3 delays early Wallerian degeneration after sciatic nerve injury.Neural regeneration research · 2022Article
- Generalized multi-SNP mediation intersection-union test.Biometrics · 2022Article
- Functional cytochrome P450 1A enzymes are induced in mouse and human islets following pollutant exposure.Diabetologia · 2020Article
- Article
- Denisovan, modern human and mouse TNFAIP3 alleles tune A20 phosphorylation and immunity.Nature immunology · 2019Article
- Comparative analysis of signaling pathways in peripheral blood from patients with Kashin-Beck disease and osteoarthritis.Experimental and therapeutic medicine · 2016Article
- Tumor necrosis factor α-induced protein-3 protects zinc transporter 8 against proinflammatory cytokine-induced downregulation.Experimental and therapeutic medicine · 2016Article
- Graph theoretic network analysis reveals protein pathways underlying cell death following neurotropic viral infection.Scientific reports · 2015Article
- Gene expression signature in endemic osteoarthritis by microarray analysis.International journal of molecular sciences · 2015Article
- Effect and mechanisms of human Wharton's jelly-derived mesenchymal stem cells on type 1 diabetes in NOD model.Endocrine · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisFor beta cells, contact with TNF-α triggers signalling cascades that converge on pathways important for cell survival and inflammation, specifically nuclear factor κB (NF-κB), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase pathways. Here, we investigated the function of baculoviral inhibitors of apoptosis repeat containing (BIRC) proteins in regulating TNF signalling cascades.
methodsTNF regulation of Birc genes was studied by mRNA expression and promoter analysis. Birc gene control of cell signalling was studied in beta cell lines, and in islets from Birc2(-/-) and Birc3(-/-) mice, and from Birc3(-/-) Birc2Δ beta cell mice that selectively lack Birc2 and Birc3 (double knockout [DKO]). Islet function was tested by intraperitoneal glucose tolerance test and transplantation.
resultsTNF-α selectively induced Birc3 in beta cells, which in turn was sufficient to drive and potentiate NF-κB reporter activity. Conversely, Birc3(-/-) islets exhibited delayed TNF-α-induced IκBα degradation with reduced expression of Ccl2 and Cxcl10. DKO islets showed a further delay in IκBα degradation kinetics. Surprisingly, DKO islets exhibited stimulus-independent and TNF-dependent hyperexpression of TNF target genes A20 (also known as Tnfaip3), Icam1, Ccl2 and Cxcl10. DKO islets showed hyperphosphorylation of the JNK-substrate, c-Jun, while a JNK-antagonist prevented increases of Icam1, Ccl2 and Cxcl10 expression. Proteosome blockade of MIN6 cells phenocopied DKO islets. DKO islets showed more rapid loss of glucose homeostasis when challenged with the inflammatory insult of transplantation. CONCLUSIONS/
interpretationBIRC3 provides a feed-forward loop, which, with BIRC2, is required to moderate the normal speed of NF-κB activation. Paradoxically, BIRC2 and BIRC3 act as a molecular brake to rein in activation of the JNK signalling pathway. Thus BIRC2 and BIRC3 fine-tune NF-κB and JNK signalling to ensure transcriptional responses are appropriately matched to extracellular inputs. This control is critical for the beta cell's stress response.
Indexed as
Identifiers
What OpenQuestion holds
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.