ArticleThe Journal of biological chemistry2014
Targeting γ-herpesvirus 68 Bcl-2-mediated down-regulation of autophagy.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 2 of them syntheses that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 45 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).Autophagy · 2016Guideline
- The molecular mechanisms of autophagy-virus interactions: from antiviral defense to viral counterstrategies.FEMS microbiology reviews · 2026Review
- Review
- Invariant BECN1 CXXC motifs bind ZnAutophagy · 2024Article
- Epstein-Barr Virus Encoded BCL2, BHRF1, Downregulates Autophagy by Noncanonical Binding of BECN1.Biochemistry · 2023Article
- Autophagy and Inflammation: Regulatory Roles in Viral Infections.Biomolecules · 2023Review
- Beth Levine's Legacy: From the Discovery of BECN1 to Therapies. A Mentees' Perspective.Frontiers in cell and developmental biology · 2022Review
- The Multi-Faceted Role of Autophagy During Animal Virus Infection.Frontiers in cellular and infection microbiology · 2022Review
- Extracellular vesicles from HTLV-1 infected cells modulate target cells and viral spread.Retrovirology · 2021Article
- Transient Unfolding and Long-Range Interactions in Viral BCL2 M11 Enable Binding to the BECN1 BH3 Domain.Biomolecules · 2020Article
- Targeting Autophagy in Innate Immune Cells: Angel or Demon During Infection and Vaccination?Frontiers in immunology · 2020Review
- Interactions between Autophagy and DNA Viruses.Viruses · 2019Review
- mTOR and Beclin1: Two key autophagy-related molecules and their roles in myocardial ischemia/reperfusion injury.Journal of cellular physiology · 2019Review
- Review
- Review
- High-Throughput Screens To Identify Autophagy Inducers That Function by Disrupting Beclin 1/Bcl-2 Binding.ACS chemical biology · 2018Article
- Beclin1 restricts RNA virus infection in plants through suppression and degradation of the viral polymerase.Nature communications · 2018Article
- SFTS phlebovirus promotes LC3-II accumulation and nonstructural protein of SFTS phlebovirus co-localizes with autophagy proteins.Scientific reports · 2018Article
- Autophagy, EVs, and Infections: A Perfect Question for a Perfect Time.Frontiers in cellular and infection microbiology · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
γ-herpesviruses (γHVs) are common human pathogens that encode homologs of the anti-apoptotic cellular Bcl-2 proteins, which are critical to viral reactivation and oncogenic transformation. The murine γHV68 provides a tractable in vivo model for understanding general features of these important human pathogens. Bcl-XL, a cellular Bcl-2 homolog, and the murine γHV68 Bcl-2 homolog, M11, both bind to a BH3 domain within the key autophagy effector Beclin 1 with comparable affinities, resulting in the down-regulation of Beclin 1-mediated autophagy. Despite this similarity, differences in residues lining the binding site of M11 and Bcl-XL dictate varying affinities for the different BH3 domain-containing proteins. Here we delineate Beclin 1 differential specificity determinants for binding to M11 or Bcl-XL by quantifying autophagy levels in cells expressing different Beclin 1 mutants and either M11 or Bcl-XL, and we show that a G120E/D121A Beclin 1 mutant selectively prevents down-regulation of Beclin 1-mediated autophagy by Bcl-XL, but not by M11. We use isothermal titration calorimetry to identify a Beclin 1 BH3 domain-derived peptide that selectively binds to M11, but not to Bcl-XL. The x-ray crystal structure of this peptide bound to M11 reveals the mechanism by which the M11 BH3 domain-binding groove accommodates this M11-specific peptide. This information was used to develop a cell-permeable peptide inhibitor that selectively inhibits M11-mediated, but not Bcl-XL-mediated, down-regulation of autophagy.
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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.