ArticleCell death and differentiation2008
BH3 domains define selective inhibitory interactions with BHRF-1 and KSHV BCL-2.
Article in Cell death and differentiation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 54 citations in OpenAlex.
- The mitochondrial ubiquitin ligase MARCHF5 cooperates with MCL1 to inhibit apoptosis in KSHV-transformed primary effusion lymphoma cell lines.PLoS pathogens · 2026Article
- The interplay between circadian rhythm components and apoptosis in health and disease.Human cell · 2026Review
- Review
- Molecular characterization, expression pattern and immunologic function ofFrontiers in immunology · 2024Article
- Epstein-Barr Virus Encoded BCL2, BHRF1, Downregulates Autophagy by Noncanonical Binding of BECN1.Biochemistry · 2023Article
- Apoptosis and Phagocytosis as Antiviral Mechanisms.Sub-cellular biochemistry · 2023Article
- Crystal Structures of Epstein-Barr Virus Bcl-2 Homolog BHRF1 Bound to Bid and Puma BH3 Motif Peptides.Viruses · 2022Article
- The evolution of regulated cell death pathways in animals and their evasion by pathogens.Physiological reviews · 2022Review
- Designing BH3-Mimetic Peptide Inhibitors for the Viral Bcl-2 Homologues A179L and BHRF1: Importance of Long-Range Electrostatic Interactions.ACS omega · 2021Article
- Article
- Viral Infections: Negative Regulators of Apoptosis and Oncogenic Factors.Biochemistry. Biokhimiia · 2020Review
- Transient Unfolding and Long-Range Interactions in Viral BCL2 M11 Enable Binding to the BECN1 BH3 Domain.Biomolecules · 2020Article
- Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins.Nature reviews. Molecular cell biology · 2019Review
- Mitochondrial Proteins Coded by Human Tumor Viruses.Frontiers in microbiology · 2018Review
- Review
- Structural and Functional Insight into Canarypox Virus CNP058 Mediated Regulation of Apoptosis.Viruses · 2017Article
- The Bcl-2 Family in Host-Virus Interactions.Viruses · 2017Review
- The Role of Gammaherpesviruses in Cancer Pathogenesis.Pathogens (Basel, Switzerland) · 2016Review
- Selective peptide inhibitors of antiapoptotic cellular and viral Bcl-2 proteins lead to cytochrome c release during latent Kaposi's sarcoma-associated herpesvirus infection.Virus research · 2016Article
- The Modulation of Apoptotic Pathways by Gammaherpesviruses.Frontiers in microbiology · 2016Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The Epstein-Barr and Kaposi's sarcoma gamma-herpesviruses (KSHVs) are associated with certain cancers, and encode B-cell leukemia/lymphoma 2 (BCL-2) homologs, BHRF-1 and KSHV BCL-2, respectively. Little is known, however, about the molecular interactions allowing viral BCL-2 homologs to mediate their anti-apoptotic function. Cellular anti-apoptotic proteins, such as BCL-2 and MCL-1, prevent death via selective interactions with pro-death BH3-only proteins. To investigate whether BHRF-1 and KSHV BCL-2 function similarly, we made recombinant BHRF-1 and KSHV BCL-2 proteins. We identified the individual binding patterns for BHRF-1 and KSHV BCL-2 to BH3 domains. These studies surprisingly showed that KSHV BCL-2 is more closely related to MCL-1 than to BCL-2, a result confirmed by sequence analysis. GST-BHRF-1 and GST-KSHV BCL-2 bound BH3-only family proteins from human cells. BHRF-1 protected mammalian cells from growth factor withdrawal, etoposide and adriamycin. We found that both BCL-2 and BHRF-1 sequestered pro-death BH3-only proteins under growth factor-deficient conditions. Finally, we tested the ability of a panel of BH3 peptides to inhibit BHRF-1 and KSHV BCL-2 function in a mitochondrial model of apoptosis. We found that each could be inhibited by the select group of BH3 peptides identified in our binding assay. Our studies define the biochemical interactions underlying BHRF-1 and KSHV BCL-2 anti-apoptotic function, and identify peptides that are prototypic inhibitors of this function.
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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.