ArticleCell death and differentiation2012
Alternative splicing of Bim and Erk-mediated Bim(EL) phosphorylation are dispensable for hematopoietic homeostasis in vivo.
Article in Cell death and differentiation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- RNA splicing in cancer cell death regulation: shedding light on the molecular mechanisms and potential clinical applications.Cell death & disease · 2026Review
- Novel selective strategies targeting the BCL-2 family to enhance clinical efficacy in ALK-rearranged non-small cell lung cancer.Cell death & disease · 2025Article
- Best evidence linking the extracellular factor TGF-β to cancer-associated alternative splicing programs.BBA advances · 2025Review
- Bufotalin Induces Oxidative Stress-Mediated Apoptosis by Blocking the ITGB4/FAK/ERK Pathway in Glioblastoma.Antioxidants (Basel, Switzerland) · 2024Article
- Enhanced MAPK signaling induced by CSF3R mutants confers dependence to DUSP1 for leukemic transformation.Blood advances · 2024Article
- MAPK-negative feedback regulation confers dependence to JAK2Leukemia · 2023Article
- FGF signaling regulates development by processes beyond canonical pathways.Genes & development · 2020Article
- A genome-scale CRISPR knock-out screen in chronic myeloid leukemia identifies novel drug resistance mechanisms along with intrinsic apoptosis and MAPK signaling.Cancer medicine · 2020Article
- miR17~92 restrains pro-apoptotic BIM to ensure survival of haematopoietic stem and progenitor cells.Cell death and differentiation · 2020Article
- 4-1BB costimulation promotes CAR T cell survival through noncanonical NF-κB signaling.Science signaling · 2020Article
- Phosphorylation alters Bim-mediated Mcl-1 stabilization and priming.The FEBS journal · 2018Article
- Article
- Dysregulation of BCL-2 family proteins by leukemia fusion genes.The Journal of biological chemistry · 2017Review
- RAG-induced DNA lesions activate proapoptotic BIM to suppress lymphomagenesis in p53-deficient mice.The Journal of experimental medicine · 2016Article
- MECHANISMS IN ENDOCRINOLOGY: Alternative splicing: the new frontier in diabetes research.European journal of endocrinology · 2016Review
- BCR-signaling-induced cell death demonstrates dependency on multiple BH3-only proteins in a murine model of B-cell lymphoma.Cell death and differentiation · 2016Article
- Mitochondrial ATF2 translocation contributes to apoptosis induction and BRAF inhibitor resistance in melanoma through the interaction of Bim with VDAC1.Oncotarget · 2015Article
- The Mutant KRAS Gene Up-regulates BCL-XL Protein via STAT3 to Confer Apoptosis Resistance That Is Reversed by BIM Protein Induction and BCL-XL Antagonism.The Journal of biological chemistry · 2015Article
- Pro-apoptotic Bim suppresses breast tumor cell metastasis and is a target gene of SNAI2.Oncogene · 2015Article
- The BCL-2 protein family, BH3-mimetics and cancer therapy.Cell death and differentiation · 2015Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 4 countries.
Funding
Abstract
The pro-apoptotic BH3-only protein Bim has a major role in hematopoietic homeostasis, particularly in the lymphocyte compartment, where it strongly affects immune function. The three major Bim isoforms (Bim(EL), Bim(L) and Bim(S)) are generated by alternative splicing. Bim(EL), the most abundant isoform, contains a unique sequence that has been reported to be the target of phosphorylation by several MAP kinases. In particular, Erk1/2 has been shown to interact with Bim(EL) through the DEF2 domain of Bim(EL) and specifically phosphorylate this isoform, thereby targeting it for ubiquitination and proteasomal degradation. To examine the physiological importance of this mechanism of regulation and of the alternative splicing of Bim, we have generated several Bim knock-in mouse strains and analyzed their hematopoietic system. Although mutation in the DEF2 domain reduces Bim(EL) degradation in some circumstances, this mutation did not significantly increase Bim's pro-apoptotic activity in vivo nor impact on the homeostasis of the hematopoietic system. We also show that Bim(EL) and Bim(L) are interchangeable, and that Bim(S) is dispensable for the function of Bim. Hence, we conclude that physiological regulation of Bim relies on mechanisms independent of its alternative splicing or the Erk-dependent phosphorylation of Bim(EL).
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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.