ArticleThe Journal of biological chemistry2011
Noxa/Bcl-2 protein interactions contribute to bortezomib resistance in human lymphoid cells.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 92 citations in OpenAlex.
- ALK-negative anaplastic large cell lymphoma is sensitive to bortezomib through Noxa upregulation and release of Bax from Bcl-2.Haematologica · 2015Trial
- Trial
- BAK and BAX: Therapeutic Targets for Acute Myocardial Infarction and Myocardial Ischemia-Reperfusion Injury.Biology · 2025Review
- Proteasome inhibition as a potential therapeutic target in thymic cancer.Cell death & disease · 2025Article
- Inhibitory Potential and Binding Thermodynamics of Scyllatoxin-Based BH3 Domain Mimetics Targeting Repressor BCL2 Proteins.Journal of molecular recognition : JMR · 2025Article
- Promoter Optimization Circumvents Bcl-2 Transgene-Mediated Suppression of Lentiviral Vector Production.Biomolecules · 2023Article
- Innate Conformational Dynamics Drive Binding Specificity in Anti-Apoptotic Proteins Mcl-1 and Bcl-2.Biochemistry · 2023Article
- Study of the Bcl-2 Interactome by BiFC Reveals Differences in the Activation Mechanism of Bax and Bak.Cells · 2023Article
- Efficacy and specificity of inhibitors of BCL-2 family protein interactions assessed by affinity measurements in live cells.Science advances · 2022Article
- Pevonedistat and azacitidine upregulate NOXA (PMAIP1) to increase sensitivity to venetoclax in preclinical models of acute myeloid leukemia.Haematologica · 2022Article
- BH3-Only Proteins Noxa and Puma Are Key Regulators of Induced Apoptosis.Life (Basel, Switzerland) · 2022Review
- Targeting Cpt1a-Bcl-2 interaction modulates apoptosis resistance and fibrotic remodeling.Cell death and differentiation · 2022Article
- Structural insights into apoptotic regulation of human Bfk as a novel Bcl-2 family member.Computational and structural biotechnology journal · 2022Article
- CDK2-Mediated Upregulation of TNFα as a Mechanism of Selective Cytotoxicity in Acute Leukemia.Cancer research · 2021Article
- Determinants of Drug Resistance in B-Cell Non-Hodgkin Lymphomas: The Case of Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia.Frontiers in oncology · 2021Review
- Mcl-1 Inhibition: Managing Malignancy in Multiple Myeloma.Frontiers in pharmacology · 2021Review
- Crosstalk between Noxa, Bcl-2, and ceramide in mediating p53-dependent apoptosis in Molt-4 human T-cell leukemia.Molecular and cellular biochemistry · 2020Article
- Targeting melanoma's MCL1 bias unleashes the apoptotic potential of BRAF and ERK1/2 pathway inhibitors.Nature communications · 2019Article
- [Bortezomib and obatoclax for dual blockade of protein degradation pathways show synergistic anti-tumor effect in human acute T lymphoblastic leukemia cells].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2019Article
- A Practical Review of Proteasome Pharmacology.Pharmacological reviews · 2019Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 4 countries.
Funding
Abstract
Previous studies have suggested that the BH3 domain of the proapoptotic Bcl-2 family member Noxa only interacts with the anti-apoptotic proteins Mcl-1 and A1 but not Bcl-2. In view of the similarity of the BH3 binding domains of these anti-apoptotic proteins as well as recent evidence that studies of isolated BH3 domains can potentially underestimate the binding between full-length Bcl-2 family members, we examined the interaction of full-length human Noxa with anti-apoptotic human Bcl-2 family members. Surface plasmon resonance using bacterially expressed proteins demonstrated that Noxa binds with mean dissociation constants (K(D)) of 3.4 nm for Mcl-1, 70 nm for Bcl-x(L), and 250 nm for wild type human Bcl-2, demonstrating selectivity but not absolute specificity of Noxa for Mcl-1. Further analysis showed that the Noxa/Bcl-2 interaction reflected binding between the Noxa BH3 domain and the Bcl-2 BH3 binding groove. Analysis of proteins expressed in vivo demonstrated that Noxa and Bcl-2 can be pulled down together from a variety of cells. Moreover, when compared with wild type Bcl-2, certain lymphoma-derived Bcl-2 mutants bound Noxa up to 20-fold more tightly in vitro, pulled down more Noxa from cells, and protected cells against killing by transfected Noxa to a greater extent. When killing by bortezomib (an agent whose cytotoxicity in Jurkat T-cell leukemia cells is dependent on Noxa) was examined, apoptosis was enhanced by the Bcl-2/Bcl-x(L) antagonist ABT-737 or by Bcl-2 down-regulation and diminished by Bcl-2 overexpression. Collectively, these observations not only establish the ability of Noxa and Bcl-2 to interact but also identify Bcl-2 overexpression as a potential mechanism of bortezomib resistance.
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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.