ArticleNucleic acids research2020
Serine-70 phosphorylated Bcl-2 prevents oxidative stress-induced DNA damage by modulating the mitochondrial redox metabolism.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 59 citations in OpenAlex.
- Nucleolin Alterations and ROS Production Associate With Sensitivity of AML Cells to Venetoclax.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Spectroscopic Signature of Apoptosis Induced by Venetoclax in Philadelphia-Positive Acute Lymphoblastic Leukemia.Analytical chemistry · 2026Article
- Article
- Chelidonine Induces Concurrent Elevation of pSer-STAT3 and Bcl-2 Levels in a Mitotic Subpopulation of Human T-Leukemia/Lymphoma Cells.International journal of molecular sciences · 2026Article
- BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- CD47 blockade-driven necroptosis complements BCL-2 inhibition-driven apoptosis in lymphoid malignancies.Journal of hematology & oncology · 2026Article
- Modified Guilu Erxian Glue restores immune tolerance in aplastic anemia by reprogramming T cell differentiation via the miR-146a/STAT1/SOCS1 axis.Frontiers in immunology · 2026Article
- Superoxide-mediated phosphorylation and stabilization of Mcl-1 by AKT underlie venetoclax resistance in hematologic malignancies.Leukemia · 2025Article
- The interplay between driver mutation and oxidative stress in colorectal cancer: from pathogenesis to therapeutics.Journal of translational medicine · 2025Review
- BCL-2 dependence is a favorable predictive marker of response to therapy for chronic lymphocytic leukemia.Molecular cancer · 2025Article
- Interplay between epigenetics, senescence and cellular redox metabolism in cancer and its therapeutic implications.Redox biology · 2024Review
- Lanthanide conjugate Pr-MPO elicits anti-cancer activity by targeting lysosomal machinery and inducing zinc-dependent cataplerosis.Cell communication and signaling : CCS · 2024Article
- Targeting ROS in cancer: rationale and strategies.Nature reviews. Drug discovery · 2024Review
- Potential New Therapies "ROS-Based" in CLL: An Innovative Paradigm in the Induction of Tumor Cell Apoptosis.Antioxidants (Basel, Switzerland) · 2024Review
- Hypomethylating agent decitabine sensitizes diffuse large B-cell lymphoma to venetoclax.Haematologica · 2024Article
- Hyperphosphorylation of BCL-2 family proteins underlies functional resistance to venetoclax in lymphoid malignancies.The Journal of clinical investigation · 2023Article
- Astaxanthin attenuates cognitive deficits in Alzheimer's disease models by reducing oxidative stress via the SIRT1/PGC-1α signaling pathway.Cell & bioscience · 2023Article
- Neuroprotective properties of anti-apoptotic BCL-2 proteins in 5xFAD mouse model of Alzheimer's disease.IBRO neuroscience reports · 2023Article
- Apoptotic cell death in disease-Current understanding of the NCCD 2023.Cell death and differentiation · 2023Review
- Discovery of the radio-protecting effect of Ecliptae Herba, its constituents and targeting p53-mediated apoptosisActa pharmaceutica Sinica. B · 2023Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bcl-2 phosphorylation at serine-70 (S70pBcl2) confers resistance against drug-induced apoptosis. Nevertheless, its specific mechanism in driving drug-resistance remains unclear. We present evidence that S70pBcl2 promotes cancer cell survival by acting as a redox sensor and modulator to prevent oxidative stress-induced DNA damage and execution. Increased S70pBcl2 levels are inversely correlated with DNA damage in chronic lymphocytic leukemia (CLL) and lymphoma patient-derived primary cells as well as in reactive oxygen species (ROS)- or chemotherapeutic drug-treated cell lines. Bioinformatic analyses suggest that S70pBcl2 is associated with lower median overall survival in lymphoma patients. Empirically, sustained expression of the redox-sensitive S70pBcl2 prevents oxidative stress-induced DNA damage and cell death by suppressing mitochondrial ROS production. Using cell lines and lymphoma primary cells, we further demonstrate that S70pBcl2 reduces the interaction of Bcl-2 with the mitochondrial complex-IV subunit-5A, thereby reducing mitochondrial complex-IV activity, respiration and ROS production. Notably, targeting S70pBcl2 with the phosphatase activator, FTY720, is accompanied by an enhanced drug-induced DNA damage and cell death in CLL primary cells. Collectively, we provide a novel facet of the anti-apoptotic Bcl-2 by demonstrating that its phosphorylation at serine-70 functions as a redox sensor to prevent drug-induced oxidative stress-mediated DNA damage and execution with potential therapeutic implications.
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