ArticleCell death and differentiation2019
By reducing global mRNA translation in several ways, 2-deoxyglucose lowers MCL-1 protein and sensitizes hemopoietic tumor cells to BH3 mimetic ABT737.
Article in Cell death and differentiation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Effects of BCL-2 and MCL-1 Inhibition on Apoptotic and Transcriptional Profiles in Acute Myeloid Leukemia.Medicina (Kaunas, Lithuania) · 2026Article
- Saga of MCL1 inhibitors in multiple myeloma.Biochemical pharmacology · 2026Review
- MCL1 modulates mTORC1 signaling to promote bioenergetics and tumorigenesis.Nature communications · 2025Article
- Asparaginase and Autophagy Inhibitors Effectively Remove Senescent Cells by Synergistically Limiting Asparagine Supply.Aging cell · 2025Article
- Glucose deprivation impairs hypoxia-inducible factor-1α synthesis.Discover oncology · 2024Article
- Oncogenic role of RNA-binding protein GNL2 in glioma: Promotion of tumor development through enhancing protein synthesis.Oncology letters · 2024Article
- The inhibition of Beclin1-dependent autophagy sensitizes PTC cells to ABT737-induced death.Genetics and molecular biology · 2024Article
- Transcriptome analysis reveals organ-specific effects of 2-deoxyglucose treatment in healthy mice.PloS one · 2024Article
- Intracellular BAPTA directly inhibits PFKFB3, thereby impeding mTORC1-driven Mcl-1 translation and killing MCL-1-addicted cancer cells.Cell death & disease · 2023Article
- Targeted inhibition of protein synthesis renders cancer cells vulnerable to apoptosis by unfolded protein response.Cell death & disease · 2023Article
- Morroniside inhibits Beclin1-dependent autophagic death and Bax-dependent apoptosis in cardiomyocytes through repressing BCL2 phosphorylation.In vitro cellular & developmental biology. Animal · 2023Article
- Venetoclax-Resistant T-ALL Cells Display Distinct Cancer Stem Cell Signatures and Enrichment of Cytokine Signaling.International journal of molecular sciences · 2023Article
- MCL-1 is a clinically targetable vulnerability in breast cancer.Cell cycle (Georgetown, Tex.) · 2022Review
- mTORC1 regulates high levels of protein synthesis in retinal ganglion cells of adult mice.The Journal of biological chemistry · 2022Article
- Emerging roles of the HECT-type E3 ubiquitin ligases in hematological malignancies.Discover oncology · 2021Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drugs targeting various pro-survival BCL-2 family members (''BH3 mimetics'') have efficacy in hemopoietic malignancies, but the non-targeted pro-survival family members can promote resistance. Pertinently, the sensitivity of some tumor cell lines to BH3 mimetic ABT737, which targets BCL-2, BCL-XL, and BCL-W but not MCL-1, is enhanced by 2-deoxyglucose (2DG). We found that 2DG augmented apoptosis induced by ABT737 in 3 of 8 human hemopoietic tumor cell lines, most strongly in pre-B acute lymphocytic leukemia cell line NALM-6, the focus of our mechanistic studies. Although 2DG can lower MCL-1 translation, how it does so is incompletely understood, in part because 2DG inhibits both glycolysis and protein glycosylation in the endoplasmic reticulum (ER). Its glycolysis inhibition lowered ATP and, through the AMPK/mTORC1 pathway, markedly reduced global protein synthesis, as did an ER integrated stress response. A dual reporter assay revealed that 2DG impeded not only cap-dependent translation but also elongation or cap-independent translation. MCL-1 protein fell markedly, whereas 12 other BCL-2 family members were unaffected. We ascribe the MCL-1 drop to the global fall in translation, exacerbated for mRNAs with a structured 5' untranslated region (5'UTR) containing potential regulatory motifs like those in MCL-1 mRNA and the short half-life of MCL-1 protein. Pertinently, 2DG downregulated two other short-lived oncoproteins, MYC and MDM2. Thus, our results support MCL-1 as a critical 2DG target, but also reveal multiple effects on global translation that may well also affect its promotion of apoptosis.
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