ArticleCancer biology & therapy2016
Bcl-2 family member Mcl-1 expression is reduced under hypoxia by the E3 ligase FBW7 contributing to BNIP3 induced cell death in glioma cells.
Article in Cancer biology & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Biomimetic three-dimensional glioma model printedInternational journal of bioprinting · 2023Article
- Bcl-2 interacting protein 3 (BNIP3) promotes tumor growth in breast cancer under hypoxic conditions through an autophagy-dependent pathway.Bioengineered · 2022Article
- PTBP3 promotes malignancy and hypoxia-induced chemoresistance in pancreatic cancer cells by ATG12 up-regulation.Journal of cellular and molecular medicine · 2020Article
- Role of Ubiquitination in PTEN Cellular Homeostasis and Its Implications in GB Drug Resistance.Frontiers in oncology · 2020Review
- Targeting the Ubiquitin System in Glioblastoma.Frontiers in oncology · 2020Review
- E3 ligase Fbw7 participates in oxidative stress‑induced myocardial cell injury via interacting with Mcl‑1.Molecular medicine reports · 2019Article
- PLK1 stabilizes a MYC-dependent kinase network in aggressive B cell lymphomas.The Journal of clinical investigation · 2018Article
- Persistent accumulation of unrepaired DNA damage in rat cortical neurons: nuclear organization and ChIP-seq analysis of damaged DNA.Acta neuropathologica communications · 2018Article
- BNIP3/Bcl-2-mediated apoptosis induced by cyclic tensile stretch in human cartilage endplate-derived stem cells.Experimental and therapeutic medicine · 2018Article
- MicroRNA-145 induces apoptosis of glioma cells by targeting BNIP3 and Notch signaling.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mcl-1 is an anti-apoptotic Bcl-2 family member that is often over-expressed in the malignant brain tumor glioblastoma (GBM). It has been previously shown that epidermal growth factor receptors up-regulate Mcl-1 contributing to a cell survival response. Hypoxia is a poor prognostic marker in glioblastoma despite the fact that hypoxic regions have areas of necrosis. Hypoxic regions of GBM also highly express the pro-cell death Bcl-2 family member BNIP3, yet when BNIP3 is overexpressed in glioma cells, it induces cell death. The reasons for this discrepancy are unclear. Herein we have found that Mcl-1 expression is reduced under hypoxia due to degradation by the E3 ligase FBW7 leading to increased hypoxia induced cell death. This cell death is reduced by EGFR activation leading to increased Mcl-1 expression under hypoxia. Conversely, BNIP3 is over-expressed in hypoxia at times when Mcl-1 expression is decreased. Knocking down BNIP3 expression reduces hypoxia cell death and Mcl-1 expression effectively blocks BNIP3 induced cell death. Of significance, BNIP3 and Mcl-1 are co-localized under hypoxia in glioma cells. These results suggest that Mcl-1 can block the ability of BNIP3 to induce cell death under hypoxia in GBM tumors.
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