ArticleOncogene2004
Cleavage of Mcl-1 by caspases impaired its ability to counteract Bim-induced apoptosis.
Article in Oncogene, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
88 citing papers in PubMed.
- Article
- Multimodal gene and targeted drug therapy for chronic myelogenous leukemia using BIM/MCL-1 chimeric nanoparticle: computational target analysis and therapeutic validation.Nano convergence · 2026Article
- Identification of a novel minor-groove DNA binder that represses mitochondrial gene expression and induces apoptosis in highly aggressive leiomyosarcoma cells.Cell death discovery · 2025Article
- Both direct and indirect suppression of MCL1 synergizes with BCLXL inhibition in preclinical models of gastric cancer.Cell death & disease · 2025Article
- PIM2 inhibition promotes MCL1 dependency in plasma cells involving integrated stress response-driven NOXA expression.Nature communications · 2025Article
- Potent combination benefit of the AKT inhibitor capivasertib and the BCL-2 inhibitor venetoclax in diffuse large B cell lymphoma.Leukemia · 2024Article
- Identification of a novel caspase cleavage motif AEAD.Virologica Sinica · 2024Article
- Effective Targeting of Melanoma Cells by Combination of Mcl-1 and Bcl-2/Bcl-xInternational journal of molecular sciences · 2024Article
- Targeting MCL-1 protein to treat cancer: opportunities and challenges.Frontiers in oncology · 2023Review
- ABT199/venetoclax potentiates the cytotoxicity of alkylating agents and fludarabine in acute myeloid leukemia cells.Oncotarget · 2022Article
- Discovery of a Novel BCL-XJournal of medicinal chemistry · 2021Article
- Article
- 2D exfoliated black phosphorus influences healthy and cancer prostate cell behaviors.Scientific reports · 2021Article
- Mcl-1 Inhibition: Managing Malignancy in Multiple Myeloma.Frontiers in pharmacology · 2021Review
- Targeting MCL-1 in hematologic malignancies: Rationale and progress.Blood reviews · 2020Review
- MARCH5 requires MTCH2 to coordinate proteasomal turnover of the MCL1:NOXA complex.Cell death and differentiation · 2020Article
- Blockade of HSP70 by VER-155008 synergistically enhances bortezomib-induced cytotoxicity in multiple myeloma.Cell stress & chaperones · 2020Article
- Article
- Saga of Mcl-1: regulation from transcription to degradation.Cell death and differentiation · 2020Review
- Discovery of Mcl-1-specific inhibitor AZD5991 and preclinical activity in multiple myeloma and acute myeloid leukemia.Nature communications · 2018Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mcl-1 is an antiapoptotic member of the Bcl-2 family that can promote cell viability. We report here that Mcl-1 is a new substrate for caspases during induction of apoptosis. Mcl-1 cleavage occurs after Asp127 and Asp157 and generates four fragments of 24, 19, 17 and 12 kDa in both intact cells and in vitro, an effect prevented by selective caspase inhibitors. As a consequence, the resulting protein that lacks the first 127 or 157 amino acids contains only the BH1-BH3 domains of Bcl-2 family members. Mutation of Asp127 and Asp157 abolishes the generation of the 24 and 12 kDa fragments and that of the 19 and 17 kDa fragments, respectively. Interestingly, when expressed in HeLa cells Mcl-1 wt and Mcl-1 Delta127 showed a markedly different intracellular distribution. Mcl-1 wt colocalized with alpha-Tubulin near the internal face of the plasma membrane, while Mcl-1 Delta127 coassociated with Bim-EL at the mitochondrial level. Coimmunoprecipitation experiments also demonstrated that Mcl1 Delta127 exhibited increased binding to Bim when compared to Mcl-1 wt. Finally, Mcl-1 wt unlike Mcl-1 Delta127 inhibited Bim-EL-induced caspase activation. Altogether, our findings demonstrate that cleavage of Mcl-1 by caspases modifies its subcellular localization, increases its association with Bim and inhibits its antiapoptotic function.
Indexed as
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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.