ArticleCell death & disease2012
Proteasome inhibition upregulates Bim and induces caspase-3-dependent apoptosis in human mast cells expressing the Kit D816V mutation.
Article in Cell death & disease, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 18 citations in OpenAlex.
- Proteasome Inhibitor-Induced Cytotoxic Mechanisms in Canine Pulmonary Adenocarcinoma Cell Lines.Veterinary and comparative oncology · 2026Article
- Proteasome inhibitor MG132 modulates signal transduction pathways in ELT3 uterine leiomyoma cells.Experimental and therapeutic medicine · 2025Article
- Article
- Fluvastatin Induces Apoptosis in Primary and Transformed Mast Cells.The Journal of pharmacology and experimental therapeutics · 2020Article
- Regulation of oxidized LDL-induced inflammatory process through NLRP3 inflammasome activation by the deubiquitinating enzyme BRCC36.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2019Article
- The Ubiquitin-Proteasome System Is Indispensable for the Maintenance of Muscle Stem Cells.Stem cell reports · 2018Article
- Degranulation of mast cells induced by gastric cancer-derived adrenomedullin prompts gastric cancer progression.Cell death & disease · 2018Article
- Tax contributes apoptosis resistance to HTLV-1-infected T cells via suppression of Bid and Bim expression.Cell death & disease · 2014Article
- MLN2238 synergizes BH3 mimetic ABT-263 in castration-resistant prostate cancer cells by induction of NOXA.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The majority of patients with systemic mastocytosis exhibit a D816V mutation in the activating loop of the Kit receptor expressed on mast cells. The Kit ligand regulates mast cell survival by transcriptional repression of the proapoptotic BH3-only protein Bim and by promoting Bim phosphorylation that makes it vulnerable for proteasomal-dependent degradation. We investigated here whether prevention of Bim degradation by a proteasomal inhibitor, MG132, would induce apoptosis in mast cells with the D816V mutation. Human umbilical cord blood-derived mast cells (CBMCs) with wild-type (wt) Kit and two different subclones of the human mast cell line-1 (HMC-1) were used for the study: HMC-1.1 with the V560G mutation in the juxtamembrane domain and HMC-1.2 carrying the V560G mutation together with the D816V mutation. MG132 at 1 μM induced apoptosis in all cell types, an effect accompanied by increased BH3-only proapoptotic protein Bim. The raise of Bim was accompanied by caspase-3 activation, and a caspase-3 inhibitor reduced MG132-induced apoptosis. Further, MG132 caused a reduction of activated Erk, a negative regulator of Bim expression, and thus Bim upregulation. We conclude that decreased phosphorylation and increased levels of Bim overcome the prosurvival effect of the D816V mutation and that the results warrant further investigations of the clinical effects of proteasomal inhibition in systemic mastocytosis.
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