ArticleCell death and differentiation2013
Apoptosis induced by the fungal pathogen gliotoxin requires a triple phosphorylation of Bim by JNK.
Article in Cell death and differentiation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 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.
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Who cites it
43 citing papers in PubMed, 66 citations in OpenAlex.
- Gliotoxin Production and Self-Defense in Filamentous Fungi.Annual review of microbiology · 2025Review
- Progress in Gliotoxin Research.Molecules (Basel, Switzerland) · 2025Review
- Manipulation of host phagocytosis by fungal pathogens and therapeutic opportunities.Nature microbiology · 2024Review
- Retracing the evolution ofMicrobiology and molecular biology reviews : MMBR · 2024Review
- The Role of the Dysregulated JNK Signaling Pathway in the Pathogenesis of Human Diseases and Its Potential Therapeutic Strategies: A Comprehensive Review.Biomolecules · 2024Review
- The Prognosis of Cancer Depends on the Interplay of Autophagy, Apoptosis, and Anoikis within the Tumor Microenvironment.Cell biochemistry and biophysics · 2023Review
- The Changes in Mitochondrial Morphology and Physiology Accompanying Apoptosis inInternational journal of molecular sciences · 2023Article
- The secretorymLife · 2023Article
- Article
- Aspergillus fumigatus Drives Tissue Damage via Iterative Assaults upon Mucosal Integrity and Immune Homeostasis.Infection and immunity · 2023Article
- Epipolythiodioxopiperazine-Based Natural Products: Building Blocks, Biosynthesis and Biological Activities.Chembiochem : a European journal of chemical biology · 2022Review
- The Toxic Mechanism of Gliotoxins and Biosynthetic Strategies for Toxicity Prevention.International journal of molecular sciences · 2021Review
- The Roles of c-Jun N-Terminal Kinase (JNK) in Infectious Diseases.International journal of molecular sciences · 2021Review
- NR4A1 enhances MKP7 expression to diminish JNK activation induced by ROS or ER-stress in pancreatic β cells for surviving.Cell death discovery · 2021Article
- Fungal-Induced Programmed Cell Death.Journal of fungi (Basel, Switzerland) · 2021Review
- Programmed Cell Death: Central Player in Fungal Infections.Trends in cell biology · 2021Review
- Fungal Toxins and Host Immune Responses.Frontiers in microbiology · 2021Review
- Coinfection withEuropean respiratory review : an official journal of the European Respiratory Society · 2020Review
- Article
- Dynein light chain binding determines complex formation and posttranslational stability of the Bcl-2 family members Bmf and Bim.Cell death and differentiation · 2020Article
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9 authors at 4 institutions in 2 countries.
Funding
Abstract
We previously reported that gliotoxin (GT), the major virulence factor of the mold Aspergillus fumigatus causing invasive aspergillosis (IA) in immunocompromised patients, induces apoptosis in a Bak-dependent manner. The signaling pathway leading to Bak activation and subsequent mitochondrial outer membrane permeabilization (MOMP) is elusive. Here, we show that GT and the supernatant of A. fumigatus (but not its GT-defective mutant) activate the JNK pathway and require a co-operative JNK-mediated BimEL phosphorylation at three sites (S100, T112 and S114) to induce apoptosis in mouse fibroblasts, human bronchial and mouse alveolar epithelial cells. Cells (i) treated with the JNK inhibitor SP600125, (ii) deleted or knocked down for JNK1/2 or Bim or (iii) carrying the BimEL triple phosphomutant S100A/T112A/S114A instead of wild-type BimEL are similarly resistant to GT-induced apoptosis. Triple-phosphorylated BimEL is more stable, redistributes from a cytoskeletal to a membrane fraction, better interacts with Bcl-2 and Bcl-xL and more effectively activates Bak than the unphosphorylated mutant. These data indicate that JNK-mediated BimEL phosphorylation at S100, T112 and S114 constitutes a novel regulatory mechanism to activate Bim in response to apoptotic stimuli.
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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.