Proapoptotic Bcl-2 Relative Bim Required for Certain Apoptotic Responses, Leukocyte Homeostasis, and to Preclude Autoimmunity
Abstract
Apoptosis can be triggered by members of the Bcl-2 protein family, such as Bim, that share only the BH3 domain with this family. Gene targeting in mice revealed important physiological roles for Bim. Lymphoid and myeloid cells accumulated, T cell development was perturbed, and most older mice accumulated plasma cells and succumbed to autoimmune kidney disease. Lymphocytes were refractory to apoptotic stimuli such as cytokine deprivation, calcium ion flux, and microtubule perturbation but not to others. Thus, Bim is required for hematopoietic homeostasis and as a barrier to autoimmunity. Moreover, particular death stimuli appear to activate apoptosis through distinct BH3-only proteins.
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Bim is upregulated as a means to eliminate auto-reactive B cells and to prevent autoimmune disease.
“Bim is upregulated as a means to eliminate auto-reactive B cells and to prevent autoimmune disease”
From The transcriptional cofactor TRIM33 prevents apoptosis in B lymphoblastic leukemia by deactivating a single enhancer (2015) · cites this paper as Bouillet et al., 1999
Pro-apoptotic BH3-only proteins are activated transcriptionally or post-translationally as specific organelles or cellular compartments experience perturbations of homeostasis, operating as cellular transducers of stress signaling.
“These pro-apoptotic members of the BCL2 protein family (which contain a single BH3 domain) are activated transcriptionally or post-translationally as specific organelles or cellular compartments experience perturbations of homeostasis, de facto operating as cellular transducers of stress signaling [60–63].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [60]
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- Authors
- Bouillet, P., Metcalf, D., Huang, D. C. S., Tarlinton, D. M., Kay, T. W. H., Köntgen, F., Adams, J. M., & Strasser, A.
- Affiliations
- Walter and Eliza Hall Institute of Medical Research (AU)
- The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia.
- Corresponding author
- Adams, Jerry M.
- Strasser, Andreas
- Venue
- Science
- Published
- 1999-11-26
- Volume
- 286
- Issue
- 5445
- Pages
- 1735-1738
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2157740207
- Cited by
- 1,504
- References
- 30
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 17 · 2023: 20 · 2022: 20 · 2021: 25 · 2020: 46 · 2019: 24 · 2018: 35 · 2017: 40 · 2016: 56 · 2015: 53 · 2014: 61 · 2013: 74 · 2012: 69
- FWCI
- 16.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (#CA 80188, R01CA043540, CA 43540, R01CA080188)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- building information modeling, Bcl-2 family proteins, BH3-only proteins, apoptosis, autoimmunity, autoimmune kidney disease, T cell development, plasma cells, hematopoietic homeostasis, cytokine deprivation, calcium flux
- MeSH terms
- Bcl-2-Like Protein 11, Animals, Autoimmune Diseases, B-Lymphocytes, Carrier Proteins, Cells, Cultured, Crosses, Genetic, Female, Glomerulonephritis, Hematopoietic Stem Cells, Homeostasis, Leukocyte Count, Leukocytes, Male, Membrane Proteins, Mice, Transgenic, Proto-Oncogene Proteins, Signal Transduction, Autoimmunity, T-Lymphocyte Subsets, Apoptosis, Gene Targeting, Proto-Oncogene Proteins c-bcl-2, Apoptosis Regulatory Proteins, Mice
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