ArticleMolecular endocrinology (Baltimore, Md.)2016
A20 Inhibits β-Cell Apoptosis by Multiple Mechanisms and Predicts Residual β-Cell Function in Type 1 Diabetes.
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Article in Molecular endocrinology (Baltimore, Md.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22citing papers in PubMed
3.2field-weighted citation impact, top 8% of its field
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- The ubiquitin-editing enzyme A20 (TNFAIP3): mechanisms of activation, biological function, diseases and therapeutic targets.Molecular biomedicine · 2026Review
- Type 2 Diabetes From the Perspective of Telomere Biology.Endocrinology, diabetes & metabolism · 2026Review
- Serum A20 level is associated with bone mineral density in male patients with type 2 diabetes mellitus.Frontiers in endocrinology · 2025Article
- Differential expression of the ubiquitin-editing enzyme A20 in gastric biopsies indicates the severity of disease.Histochemistry and cell biology · 2024Article
- A20 negatively regulates necroptosis-induced microglia/macrophages polarization and mediates cerebral ischemic tolerance via inhibiting the ubiquitination of RIP3.Cell death & disease · 2024Article
- The N6-methyladenosine RNA epigenetic modification modulates the amplification of coxsackievirus B1 in human pancreatic beta cells.Frontiers in microbiology · 2024Article
- NF-κB-inducing kinase (NIK) is activated in pancreatic β-cells but does not contribute to the development of diabetes.Cell death & disease · 2022Article
- Transcript Expression Profiles and MicroRNA Regulation Indicate an Upregulation of Processes Linked to Oxidative Stress, DNA Repair, Cell Death, and Inflammation in Type 1 Diabetes Mellitus Patients.Journal of diabetes research · 2022Article
- Review
- Article
- The Ubiquitin System and A20: Implications in Health and Disease.Journal of dental research · 2021Review
- Review
- A20 at the Crossroads of Cell Death, Inflammation, and Autoimmunity.Cold Spring Harbor perspectives in biology · 2020Review
- Advances in Knowledge of Candidate Genes Acting at the Beta-Cell Level in the Pathogenesis of T1DM.Frontiers in endocrinology · 2020Review
- A20 Restricts Inflammatory Response and Desensitizes Gingival Keratinocytes to Apoptosis.Frontiers in immunology · 2020Article
- Genetic and Environmental Interaction in Type 1 Diabetes: a Relationship Between Genetic Risk Alleles and Molecular Traits of Enterovirus Infection?Current diabetes reports · 2019Review
- Expanding the spectrum of A20 haploinsufficiency in two Chinese families: cases report.BMC medical genetics · 2019Article
- Neuroligin-2-derived peptide-covered polyamidoamine-based (PAMAM) dendrimers enhance pancreatic β-cells' proliferation and functions.MedChemComm · 2019Article
- CRISPR/cas9 mediated knockout of an intergenic variant rs6927172 identified IL-20RA as a new risk gene for multiple autoimmune diseases.Genes and immunity · 2019Article
- Type 1 Diabetes Candidate Genes Linked to Pancreatic Islet Cell Inflammation and Beta-Cell Apoptosis.Genes · 2017Review
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Authors and funding
15 authors at 6 institutions in 3 countries.
Makiko FukayaUniversité Libre de Bruxelles Center for Diabetes Research (M.F., K.M., D.D., E.C.V., A.K.C.), Free University Brussels, 1070 Brussels, Belgium; Copenhagen Diabetes Research Center (C.A.B., L.B.N., M.L.A., H.B.M., F.P., J.S.), Department of Pediatrics E, Copenhagen University Hospital Herlev, DL-2730 Herlev, Denmark; Inflammation Research Center (L.C., R.B., G.v.L.), Vlaams Instituut voor Biotechnologie, 9052 Gent, Belgium; Department of Biomedical Molecular Biology (L.C., R.B., G.v.L.), 9052 Gent University, Gent, Belgium; Laboratory of Endocrine Pancreas and Metabolism (E.C.V.), Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, 13083-970 Campinas, Brazil; and Department of Development and Cellular Biology (F.O.), Institute of Biomedical Sciences, 05508-900 São Paulo University, São Paulo, Brazil.
Caroline A BrorssonUniversité Libre de Bruxelles Center for Diabetes Research (M.F., K.M., D.D., E.C.V., A.K.C.), Free University Brussels, 1070 Brussels, Belgium; Copenhagen Diabetes Research Center (C.A.B., L.B.N., M.L.A., H.B.M., F.P., J.S.), Department of Pediatrics E, Copenhagen University Hospital Herlev, DL-2730 Herlev, Denmark; Inflammation Research Center (L.C., R.B., G.v.L.), Vlaams Instituut voor Biotechnologie, 9052 Gent, Belgium; Department of Biomedical Molecular Biology (L.C., R.B., G.v.L.), 9052 Gent University, Gent, Belgium; Laboratory of Endocrine Pancreas and Metabolism (E.C.V.), Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, 13083-970 Campinas, Brazil; and Department of Development and Cellular Biology (F.O.), Institute of Biomedical Sciences, 05508-900 São Paulo University, São Paulo, Brazil.
Kira MeyerovichUniversité Libre de Bruxelles Center for Diabetes Research (M.F., K.M., D.D., E.C.V., A.K.C.), Free University Brussels, 1070 Brussels, Belgium; Copenhagen Diabetes Research Center (C.A.B., L.B.N., M.L.A., H.B.M., F.P., J.S.), Department of Pediatrics E, Copenhagen University Hospital Herlev, DL-2730 Herlev, Denmark; Inflammation Research Center (L.C., R.B., G.v.L.), Vlaams Instituut voor Biotechnologie, 9052 Gent, Belgium; Department of Biomedical Molecular Biology (L.C., R.B., G.v.L.), 9052 Gent University, Gent, Belgium; Laboratory of Endocrine Pancreas and Metabolism (E.C.V.), Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, 13083-970 Campinas, Brazil; and Department of Development and Cellular Biology (F.O.), Institute of Biomedical Sciences, 05508-900 São Paulo University, São Paulo, Brazil.
Leen CatrysseUniversité Libre de Bruxelles Center for Diabetes Research (M.F., K.M., D.D., E.C.V., A.K.C.), Free University Brussels, 1070 Brussels, Belgium; Copenhagen Diabetes Research Center (C.A.B., L.B.N., M.L.A., H.B.M., F.P., J.S.), Department of Pediatrics E, Copenhagen University Hospital Herlev, DL-2730 Herlev, Denmark; Inflammation Research Center (L.C., R.B., G.v.L.), Vlaams Instituut voor Biotechnologie, 9052 Gent, Belgium; Department of Biomedical Molecular Biology (L.C., R.B., G.v.L.), 9052 Gent University, Gent, Belgium; Laboratory of Endocrine Pancreas and Metabolism (E.C.V.), Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, 13083-970 Campinas, Brazil; and Department of Development and Cellular Biology (F.O.), Institute of Biomedical Sciences, 05508-900 São Paulo University, São Paulo, Brazil.
Diane DelarocheUniversité Libre de Bruxelles Center for Diabetes Research (M.F., K.M., D.D., E.C.V., A.K.C.), Free University Brussels, 1070 Brussels, Belgium; Copenhagen Diabetes Research Center (C.A.B., L.B.N., M.L.A., H.B.M., F.P., J.S.), Department of Pediatrics E, Copenhagen University Hospital Herlev, DL-2730 Herlev, Denmark; Inflammation Research Center (L.C., R.B., G.v.L.), Vlaams Instituut voor Biotechnologie, 9052 Gent, Belgium; Department of Biomedical Molecular Biology (L.C., R.B., G.v.L.), 9052 Gent University, Gent, Belgium; Laboratory of Endocrine Pancreas and Metabolism (E.C.V.), Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, 13083-970 Campinas, Brazil; and Department of Development and Cellular Biology (F.O.), Institute of Biomedical Sciences, 05508-900 São Paulo University, São Paulo, Brazil.
Emerielle C VanzelaUniversité Libre de Bruxelles Center for Diabetes Research (M.F., K.M., D.D., E.C.V., A.K.C.), Free University Brussels, 1070 Brussels, Belgium; Copenhagen Diabetes Research Center (C.A.B., L.B.N., M.L.A., H.B.M., F.P., J.S.), Department of Pediatrics E, Copenhagen University Hospital Herlev, DL-2730 Herlev, Denmark; Inflammation Research Center (L.C., R.B., G.v.L.), Vlaams Instituut voor Biotechnologie, 9052 Gent, Belgium; Department of Biomedical Molecular Biology (L.C., R.B., G.v.L.), 9052 Gent University, Gent, Belgium; Laboratory of Endocrine Pancreas and Metabolism (E.C.V.), Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, 13083-970 Campinas, Brazil; and Department of Development and Cellular Biology (F.O.), Institute of Biomedical Sciences, 05508-900 São Paulo University, São Paulo, Brazil.
Fernanda OrtisUniversité Libre de Bruxelles Center for Diabetes Research (M.F., K.M., D.D., E.C.V., A.K.C.), Free University Brussels, 1070 Brussels, Belgium; Copenhagen Diabetes Research Center (C.A.B., L.B.N., M.L.A., H.B.M., F.P., J.S.), Department of Pediatrics E, Copenhagen University Hospital Herlev, DL-2730 Herlev, Denmark; Inflammation Research Center (L.C., R.B., G.v.L.), Vlaams Instituut voor Biotechnologie, 9052 Gent, Belgium; Department of Biomedical Molecular Biology (L.C., R.B., G.v.L.), 9052 Gent University, Gent, Belgium; Laboratory of Endocrine Pancreas and Metabolism (E.C.V.), Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, 13083-970 Campinas, Brazil; and Department of Development and Cellular Biology (F.O.), Institute of Biomedical Sciences, 05508-900 São Paulo University, São Paulo, Brazil.
Rudi BeyaertUniversité Libre de Bruxelles Center for Diabetes Research (M.F., K.M., D.D., E.C.V., A.K.C.), Free University Brussels, 1070 Brussels, Belgium; Copenhagen Diabetes Research Center (C.A.B., L.B.N., M.L.A., H.B.M., F.P., J.S.), Department of Pediatrics E, Copenhagen University Hospital Herlev, DL-2730 Herlev, Denmark; Inflammation Research Center (L.C., R.B., G.v.L.), Vlaams Instituut voor Biotechnologie, 9052 Gent, Belgium; Department of Biomedical Molecular Biology (L.C., R.B., G.v.L.), 9052 Gent University, Gent, Belgium; Laboratory of Endocrine Pancreas and Metabolism (E.C.V.), Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, 13083-970 Campinas, Brazil; and Department of Development and Cellular Biology (F.O.), Institute of Biomedical Sciences, 05508-900 São Paulo University, São Paulo, Brazil.
Lotte B NielsenUniversité Libre de Bruxelles Center for Diabetes Research (M.F., K.M., D.D., E.C.V., A.K.C.), Free University Brussels, 1070 Brussels, Belgium; Copenhagen Diabetes Research Center (C.A.B., L.B.N., M.L.A., H.B.M., F.P., J.S.), Department of Pediatrics E, Copenhagen University Hospital Herlev, DL-2730 Herlev, Denmark; Inflammation Research Center (L.C., R.B., G.v.L.), Vlaams Instituut voor Biotechnologie, 9052 Gent, Belgium; Department of Biomedical Molecular Biology (L.C., R.B., G.v.L.), 9052 Gent University, Gent, Belgium; Laboratory of Endocrine Pancreas and Metabolism (E.C.V.), Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, 13083-970 Campinas, Brazil; and Department of Development and Cellular Biology (F.O.), Institute of Biomedical Sciences, 05508-900 São Paulo University, São Paulo, Brazil.
Marie L AndersenUniversité Libre de Bruxelles Center for Diabetes Research (M.F., K.M., D.D., E.C.V., A.K.C.), Free University Brussels, 1070 Brussels, Belgium; Copenhagen Diabetes Research Center (C.A.B., L.B.N., M.L.A., H.B.M., F.P., J.S.), Department of Pediatrics E, Copenhagen University Hospital Herlev, DL-2730 Herlev, Denmark; Inflammation Research Center (L.C., R.B., G.v.L.), Vlaams Instituut voor Biotechnologie, 9052 Gent, Belgium; Department of Biomedical Molecular Biology (L.C., R.B., G.v.L.), 9052 Gent University, Gent, Belgium; Laboratory of Endocrine Pancreas and Metabolism (E.C.V.), Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, 13083-970 Campinas, Brazil; and Department of Development and Cellular Biology (F.O.), Institute of Biomedical Sciences, 05508-900 São Paulo University, São Paulo, Brazil.
Henrik B MortensenUniversité Libre de Bruxelles Center for Diabetes Research (M.F., K.M., D.D., E.C.V., A.K.C.), Free University Brussels, 1070 Brussels, Belgium; Copenhagen Diabetes Research Center (C.A.B., L.B.N., M.L.A., H.B.M., F.P., J.S.), Department of Pediatrics E, Copenhagen University Hospital Herlev, DL-2730 Herlev, Denmark; Inflammation Research Center (L.C., R.B., G.v.L.), Vlaams Instituut voor Biotechnologie, 9052 Gent, Belgium; Department of Biomedical Molecular Biology (L.C., R.B., G.v.L.), 9052 Gent University, Gent, Belgium; Laboratory of Endocrine Pancreas and Metabolism (E.C.V.), Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, 13083-970 Campinas, Brazil; and Department of Development and Cellular Biology (F.O.), Institute of Biomedical Sciences, 05508-900 São Paulo University, São Paulo, Brazil.
Flemming PociotUniversité Libre de Bruxelles Center for Diabetes Research (M.F., K.M., D.D., E.C.V., A.K.C.), Free University Brussels, 1070 Brussels, Belgium; Copenhagen Diabetes Research Center (C.A.B., L.B.N., M.L.A., H.B.M., F.P., J.S.), Department of Pediatrics E, Copenhagen University Hospital Herlev, DL-2730 Herlev, Denmark; Inflammation Research Center (L.C., R.B., G.v.L.), Vlaams Instituut voor Biotechnologie, 9052 Gent, Belgium; Department of Biomedical Molecular Biology (L.C., R.B., G.v.L.), 9052 Gent University, Gent, Belgium; Laboratory of Endocrine Pancreas and Metabolism (E.C.V.), Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, 13083-970 Campinas, Brazil; and Department of Development and Cellular Biology (F.O.), Institute of Biomedical Sciences, 05508-900 São Paulo University, São Paulo, Brazil.
Geert van LooUniversité Libre de Bruxelles Center for Diabetes Research (M.F., K.M., D.D., E.C.V., A.K.C.), Free University Brussels, 1070 Brussels, Belgium; Copenhagen Diabetes Research Center (C.A.B., L.B.N., M.L.A., H.B.M., F.P., J.S.), Department of Pediatrics E, Copenhagen University Hospital Herlev, DL-2730 Herlev, Denmark; Inflammation Research Center (L.C., R.B., G.v.L.), Vlaams Instituut voor Biotechnologie, 9052 Gent, Belgium; Department of Biomedical Molecular Biology (L.C., R.B., G.v.L.), 9052 Gent University, Gent, Belgium; Laboratory of Endocrine Pancreas and Metabolism (E.C.V.), Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, 13083-970 Campinas, Brazil; and Department of Development and Cellular Biology (F.O.), Institute of Biomedical Sciences, 05508-900 São Paulo University, São Paulo, Brazil.
Joachim StørlingUniversité Libre de Bruxelles Center for Diabetes Research (M.F., K.M., D.D., E.C.V., A.K.C.), Free University Brussels, 1070 Brussels, Belgium; Copenhagen Diabetes Research Center (C.A.B., L.B.N., M.L.A., H.B.M., F.P., J.S.), Department of Pediatrics E, Copenhagen University Hospital Herlev, DL-2730 Herlev, Denmark; Inflammation Research Center (L.C., R.B., G.v.L.), Vlaams Instituut voor Biotechnologie, 9052 Gent, Belgium; Department of Biomedical Molecular Biology (L.C., R.B., G.v.L.), 9052 Gent University, Gent, Belgium; Laboratory of Endocrine Pancreas and Metabolism (E.C.V.), Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, 13083-970 Campinas, Brazil; and Department of Development and Cellular Biology (F.O.), Institute of Biomedical Sciences, 05508-900 São Paulo University, São Paulo, Brazil.
Alessandra K CardozoUniversité Libre de Bruxelles Center for Diabetes Research (M.F., K.M., D.D., E.C.V., A.K.C.), Free University Brussels, 1070 Brussels, Belgium; Copenhagen Diabetes Research Center (C.A.B., L.B.N., M.L.A., H.B.M., F.P., J.S.), Department of Pediatrics E, Copenhagen University Hospital Herlev, DL-2730 Herlev, Denmark; Inflammation Research Center (L.C., R.B., G.v.L.), Vlaams Instituut voor Biotechnologie, 9052 Gent, Belgium; Department of Biomedical Molecular Biology (L.C., R.B., G.v.L.), 9052 Gent University, Gent, Belgium; Laboratory of Endocrine Pancreas and Metabolism (E.C.V.), Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, 13083-970 Campinas, Brazil; and Department of Development and Cellular Biology (F.O.), Institute of Biomedical Sciences, 05508-900 São Paulo University, São Paulo, Brazil.
Université Libre de Bruxelles · BEHerlev Hospital · DKCopenhagen University Hospital · DKGhent University · BEUniversidade de São Paulo · BRVlaams Instituut voor Biotechnologie · BE
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of the transcription factor nuclear factor kappa B (NFkB) contributes to β-cell death in type 1 diabetes (T1D). Genome-wide association studies have identified the gene TNF-induced protein 3 (TNFAIP3), encoding for the zinc finger protein A20, as a susceptibility locus for T1D. A20 restricts NF-κB signaling and has strong antiapoptotic activities in β-cells. Although the role of A20 on NF-κB inhibition is well characterized, its other antiapoptotic functions are largely unknown. By studying INS-1E cells and rat dispersed islet cells knocked down or overexpressing A20 and islets isolated from the β-cell-specific A20 knockout mice, we presently demonstrate that A20 has broader effects in β-cells that are not restricted to inhibition of NF-κB. These involves, suppression of the proapoptotic mitogen-activated protein kinase c-Jun N-terminal kinase (JNK), activation of survival signaling via v-akt murine thymoma viral oncogene homolog (Akt) and consequently inhibition of the intrinsic apoptotic pathway. Finally, in a cohort of T1D children, we observed that the risk allele of the rs2327832 single nucleotide polymorphism of TNFAIP3 predicted lower C-peptide and higher hemoglobin A1c (HbA1c) levels 12 months after disease onset, indicating reduced residual β-cell function and impaired glycemic control. In conclusion, our results indicate a critical role for A20 in the regulation of β-cell survival and unveil novel mechanisms by which A20 controls β-cell fate. Moreover, we identify the single nucleotide polymorphism rs2327832 of TNFAIP3 as a possible prognostic marker for diabetes outcome in children with T1D.
Indexed as
AnimalsApoptosisChildCysteine EndopeptidasesDiabetes Mellitus, Type 1Disease Models, AnimalFemaleHumansInsulin-Secreting CellsIntracellular Signaling Peptides and ProteinsJNK Mitogen-Activated Protein KinasesMaleMiceMice, KnockoutMitogen-Activated Protein KinasesPolymorphism, Single NucleotideCysteine EndopeptidasesIntracellular Signaling Peptides and ProteinsJNK Mitogen-Activated Protein KinasesMitogen-Activated Protein KinasesTnfaip3 protein, mouseTumor Necrosis Factor alpha-Induced Protein 3
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