ArticleProceedings of the National Academy of Sciences of the United States of America2013
Proapoptotic Bak and Bax guard against fatal systemic and organ-specific autoimmune disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 49 citations in OpenAlex.
- Endoplasmic Reticulum-Dependent Apoptotic Response to Cellular Stress in Patients with Rheumatoid Arthritis.International journal of molecular sciences · 2025Article
- Directly targeting BAX for drug discovery: Therapeutic opportunities and challenges.Acta pharmaceutica Sinica. B · 2024Review
- Gene Expression Profiling to Unfolded Proteins Response as a Risk Modulator of Patients with Rheumatoid Arthritis.International journal of molecular sciences · 2024Article
- Apoptotic cell death in disease-Current understanding of the NCCD 2023.Cell death and differentiation · 2023Review
- Pro-apoptotic Bax mRNA expression: A novel predictor for systemic lupus erythematosus disease flare-up.Archives of rheumatology · 2023Article
- Expression of Autoimmunity-Related Genes in Melanoma.Cancers · 2022Article
- A Glimpse of Programmed Cell Death Among Bacteria, Animals, and Plants.Frontiers in cell and developmental biology · 2021Review
- Role of Extrinsic Apoptotic Signaling Pathway during Definitive Erythropoiesis in Normal Patients and in Patients with β-Thalassemia.International journal of molecular sciences · 2020Review
- The Multifaceted Roles of the BCL-2 Family Member BOK.Frontiers in cell and developmental biology · 2020Review
- Targeting BCL-2 regulated apoptosis in cancer.Open biology · 2018Review
- Bim suppresses the development of SLE by limiting myeloid inflammatory responses.The Journal of experimental medicine · 2017Article
- The BH3-only proteins BIM and PUMA are not critical for the reticulocyte apoptosis caused by loss of the pro-survival protein BCL-XL.Cell death & disease · 2017Article
- Overexpression of Mcl-1 exacerbates lymphocyte accumulation and autoimmune kidney disease in lpr mice.Cell death and differentiation · 2017Article
- Life and Death of Activated T Cells: How Are They Different from Naïve T Cells?Frontiers in immunology · 2017Review
- NFκB1 is essential to prevent the development of multiorgan autoimmunity by limiting IL-6 production in follicular B cells.The Journal of experimental medicine · 2016Article
- Inhibition of MARCH5 ubiquitin ligase abrogates MCL1-dependent resistance to BH3 mimetics via NOXA.Oncotarget · 2016Article
- Thirty years of BCL-2: translating cell death discoveries into novel cancer therapies.Nature reviews. Cancer · 2016Review
- Impact of the combined loss of BOK, BAX and BAK on the hematopoietic system is slightly more severe than compound loss of BAX and BAK.Cell death & disease · 2015Article
- bak deletion stimulates gastric epithelial proliferation and enhances Helicobacter felis-induced gastric atrophy and dysplasia in mice.American journal of physiology. Gastrointestinal and liver physiology · 2015Article
- Engineered cellular gene-replacement platform for selective and inducible proteolytic profiling.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Dysregulation of the "intrinsic" apoptotic pathway is associated with the development of cancer and autoimmune disease. Bak and Bax are two proapoptotic members of the Bcl-2 protein family with overlapping, essential roles in the intrinsic apoptotic pathway. Their activity is critical for the control of cell survival during lymphocyte development and homeostasis, best demonstrated by defects in thymic T-cell differentiation and peripheral lymphoid homeostasis caused by their combined loss. Because most bak(-/-)bax(-/-) mice die perinatally, the roles of Bax and Bak in immunological tolerance and prevention of autoimmune disease remain unclear. We show that mice reconstituted with a Bak/Bax doubly deficient hematopoietic compartment develop a fatal systemic lupus erythematosus-like autoimmune disease characterized by hypergammaglobulinemia, autoantibodies, lymphadenopathy, glomerulonephritis, and vasculitis. Importantly, these mice also develop a multiorgan autoimmune disease with autoantibodies against most solid glandular structures and evidence of glandular atrophy and necrotizing vasculitis. Interestingly, similar albeit less severe pathology was observed in mice containing a hematopoietic compartment deficient for only Bak, a phenotype reminiscent of the disease seen in patients with point mutations in BAK. These studies demonstrate a critical role for Bak and an ancillary role for Bax in safeguarding immunological tolerance and prevention of autoimmune disease. This suggests that direct activators of the intrinsic apoptotic pathway, such as BH3 mimetics, may be useful for treatment of diverse autoimmune diseases.
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