ArticleThe Journal of biological chemistry2013
Bim, a proapoptotic protein, up-regulated via transcription factor E2F1-dependent mechanism, functions as a prosurvival molecule in cancer.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 84 citations in OpenAlex.
- Role of the Transcription Factor CREB in Ethanol-Induced Endoplasmic Reticulum Stress and Apoptosis in PC12 Cells.Biology · 2025Article
- Fatty acid synthase (FASN) inhibition cooperates with BH3 mimetic drugs to overcome resistance to mitochondrial apoptosis in pancreatic cancer.Neoplasia (New York, N.Y.) · 2025Article
- Dynamic interactions of dimeric hub proteins underlie their diverse functions and structures: A comparative analysis of 14-3-3 and LC8.The Journal of biological chemistry · 2025Review
- The BCL2 family: from apoptosis mechanisms to new advances in targeted therapy.Signal transduction and targeted therapy · 2025Review
- Circumvention of Gefitinib Resistance by Repurposing Flunarizine via Histone Deacetylase Inhibition.ACS pharmacology & translational science · 2023Article
- Targeted Strategies for Degradation of Key Transmembrane Proteins in Cancer.Biotech (Basel (Switzerland)) · 2023Review
- α-Synuclein upregulates bim-mediated apoptosis by negatively regulating endogenous GCN5.Aging · 2022Article
- A mitochondrial unfolded protein response inhibitor suppresses prostate cancer growth in mice via HSP60.The Journal of clinical investigation · 2022Article
- The MreA Metal-Binding Sites C40, H65, and C69 Play a Critical Role in the Metal Tolerance of Pseudomonas putida KT2440.Current microbiology · 2022Article
- HRK inhibits colorectal cancer cells proliferation by suppressing the PI3K/AKT/mTOR pathway.Frontiers in oncology · 2022Article
- Upcoming treatments for morphea.Immunity, inflammation and disease · 2021Review
- Mitochondrial dysfunction, UPRCell & bioscience · 2021Review
- Review
- [Expression and Clinical Significance of Lipocalin-2 in the Serum of Lung Cancer Patients].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2021Article
- Brucella suppress STING expression via miR-24 to enhance infection.PLoS pathogens · 2020Article
- The chaperone Hsp70 is a BH3 receptor activated by the pro-apoptotic Bim to stabilize anti-apoptotic clients.The Journal of biological chemistry · 2020Article
- Mitochondrial Stress Response and Cancer.Trends in cancer · 2020Review
- Biological Functions and Therapeutic Potential of Lipocalin 2 in Cancer.International journal of molecular sciences · 2020Review
- Molecular insights on cytochrome c and nucleotide regulation of apoptosome function and its implication in cancer.Biochimica et biophysica acta. Molecular cell research · 2020Article
- KRAS and BRAF mutations induce anoikis resistance and characteristic 3D phenotypes in Caco‑2 cells.Molecular medicine reports · 2019Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Proapoptotic Bcl-2 homology 3-only protein Bim plays an important role in Bax/Bak-mediated cytochrome c release and apoptosis. Here, we provide evidence for a novel prosurvival function of Bim in cancer cells. Bim was constitutively overexpressed in multiple prostate and breast cancer cells as well as in primary tumor cells. Quantitative real time PCR analysis showed that Bim was transcriptionally up-regulated. We have identified eight endogenous E2F1-binding sites on the Bim promoter using in silico analysis. Luciferase assay demonstrated that Bim expression was E2F1-dependent as mutation of the E2F1-binding sites on the Bim promoter inhibited luciferase activities. In support, E2F1 silencing led to the loss of Bim expression in cancer cells. Bim primarily localized to mitochondrial and cytoskeleton-associated fractions. Bim silencing or microinjection of anti-Bim antibodies into the cell cytoplasm resulted in cell rounding, detachment, and subsequent apoptosis. We observed up-regulation of prosurvival proteins Bcl-xL and Mcl-1, which sequester Bim in cancer cells. In addition, a phosphorylated form of Bim was also elevated in cancer cells. These findings suggest that the constitutively overexpressed Bim may function as a prosurvival molecule in epithelial cancer cells, and phosphorylation and association with Bcl-xL/Mcl-1 block its proapoptotic functions.
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Registered trials
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