ArticleCancer research2012
BCL2 suppresses PARP1 function and nonapoptotic cell death.
Article in Cancer research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 54 citations in OpenAlex.
- GX15-070 enhances niraparib efficacy in ovarian cancer by promoting a shift in Mcl1-mediated DNA repair pathway from HR to NHEJ.Journal of translational medicine · 2025Article
- Exploring the Role of BCL2 Interactome in Cancer: A Protein/Residue Interaction Network Analysis.Biology · 2025Article
- Mitochondrial Factors in the Cell Nucleus.International journal of molecular sciences · 2023Review
- Bcl-2 family inhibitors sensitize human cancer models to therapy.Cell death & disease · 2023Article
- Dual targeting of BCL-2 and MCL-1 in the presence of BAX breaks venetoclax resistance in human small cell lung cancer.British journal of cancer · 2023Article
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- Apnea of prematurity induces short and long-term development-related transcriptional changes in the murine cerebellum.Current research in neurobiology · 2023Article
- Glioblastoma-Derived Exosomes as Nanopharmaceutics for Improved Glioma Treatment.Pharmaceutics · 2022Article
- The human vault RNA enhances tumorigenesis and chemoresistance through the lysosome in hepatocellular carcinoma.Autophagy · 2022Article
- MS-275 (Entinostat) Promotes Radio-Sensitivity in PAX3-FOXO1 Rhabdomyosarcoma Cells.International journal of molecular sciences · 2021Article
- Withaferin A triggers G2/M arrest and intrinsic apoptosis in glioblastoma cells via ATF4-ATF3-CHOP axis.Cell proliferation · 2020Article
- Caspase-Dependent Apoptosis in Prostate Cancer Cells and Zebrafish by Corchorusoside C from Streptocaulon juventas.Journal of natural products · 2019Article
- BCL-2 family isoforms in apoptosis and cancer.Cell death & disease · 2019Review
- Article
- Expression of Bcl-2 is a favorable prognostic biomarker in lung squamous cell carcinoma.Oncology letters · 2018Article
- BH3 mimetics suppress CXCL12 expression in human malignant peripheral nerve sheath tumor cells.Oncotarget · 2017Article
- Astrocytes promote progression of breast cancer metastases to the brain via a KISS1-mediated autophagy.Autophagy · 2017Article
- Sil1-Mutant Mice Elucidate Chaperone Function in Neurological Disorders.Journal of neuromuscular diseases · 2016Article
- Novel drug targets for personalized precision medicine in relapsed/refractory diffuse large B-cell lymphoma: a comprehensive review.Molecular cancer · 2015Review
- BCL2 is an independent predictor of outcome in basal-like triple-negative breast cancers treated with adjuvant anthracycline-based chemotherapy.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
BCL2 suppresses apoptosis by binding the BH3 domain of proapoptotic factors and thereby regulating outer mitochondrial membrane permeabilization. Many tumor types, including B-cell lymphomas and chronic lymphocytic leukemia, are dependent on BCL2 for survival but become resistant to apoptosis after treatment. Here, we identified a direct interaction between the antiapoptotic protein BCL2 and the enzyme PARP1, which suppresses PARP1 enzymatic activity and inhibits PARP1-dependent DNA repair in diffuse large B-cell lymphoma cells. The BH3 mimetic ABT-737 displaced PARP1 from BCL2 in a dose-dependent manner, reestablishing PARP1 activity and DNA repair and promoting nonapoptotic cell death. This form of cell death was unaffected by resistance to single-agent ABT-737 that results from upregulation of antiapoptotic BCL2 family members. On the basis of the ability of BCL2 to suppress PARP1 function, we hypothesized that ectopic BCL2 expression would kill PARP inhibitor-sensitive cells. Strikingly, BCL2 expression reduced the survival of PARP inhibitor-sensitive breast cancer and lung cancer cells by 90% to 100%, and these effects were reversed by ABT-737. Taken together, our findings show that a novel interaction between BCL2 and PARP1 blocks PARP1 enzymatic activity and suppresses PARP1-dependent repair. Targeted disruption of the BCL2-PARP1 interaction therefore may represent a potential therapeutic approach for BCL2-expressing tumors resistant to apoptosis.
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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.