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Rice blast, caused by , is a major threat to global rice production. This study explores the antifungal potential of the immunosuppressant FK506 and identifies its target protein, MoFpr1 (FK506-binding protein 1B). FK506 inhibited mycelial growth, appressorium formation, and pathogenicity of in an MoFpr1-dependent manner. Mechanistic analyses revealed that FK506 impairs autophagy and ubiquitination, supported by transcriptomic and metabolomic data. Structural studies using X-ray crystallography and site-directed mutagenesis confirmed the direct interaction between FK506 and MoFpr1, highlighting the importance of residues Gly95 and Ile97. Furthermore, FK506 demonstrated broad-spectrum antifungal activity against various plant pathogens and effectively controlled rice blast in laboratory, net-chamber, and field trials with minimal phytotoxicity. These findings position FK506 as a promising antifungal agent and offer insights into its molecular mechanism, suggesting its potential for sustainable plant disease management.
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http://dx.doi.org/10.1021/acs.jafc.5c03733 | DOI Listing |
Vet Microbiol
September 2025
Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China; Shanghai Key Laboratory of Veterinary Biotechnology, Shanghai 200240, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou Unive
Bovine coronavirus (BCoV), a member of the Betacoronavirus genus, causes severe calf gastroenteritis and respiratory disease, resulting in a significant loss of livestock. Coronavirus non-structural protein 14 (nsp14) is involved in viral RNA replication and modification and subverts host immune regulatory pathways to facilitate immune evasion. In this study, we demonstrated that BCoV nsp14 mediates TNF receptor-associated factor 3 (TRAF3) degradation through the coordinated targeting of the ubiquitin-proteasome and autophagy-lysosomal pathways, thereby potentiating viral replication.
View Article and Find Full Text PDFPlant Cell
September 2025
Department of Plant Sciences, College of Biological Sciences, State Key Laboratory of Plant Environmental Resilience, China Agricultural University, Beijing 100193, China.
Plant thermomorphogenesis is a critical adaptive response to elevated ambient temperatures. The transcription factor PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) integrates diverse environmental and phytohormone signals to coordinate thermoresponsive growth. However, the cellular mechanisms underlying plant thermomorphogenic growth remain poorly understood.
View Article and Find Full Text PDFAutophagy
September 2025
Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Immune checkpoint inhibitors (ICIs) can re-active the immune response and induce a complete response in mismatch repair-deficient and microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC). However, most CRCs exhibit proficient mismatch repair and microsatellite stable (pMMR/MSS) phenotypes with limited immunotherapy response because of sparse intratumoral CD8 T-lymphocyte infiltration. Cellular senescence has been reported to involve immune cell infiltration through a senescence-associated secretory phenotype (SASP).
View Article and Find Full Text PDFAm J Physiol Cell Physiol
September 2025
Institute of Pharmacology and Toxicology, Goethe University Frankfurt, Frankfurt, Germany.
The A20 binding inhibitor of nuclear factor-kappa B (NF-κB)-1 (ABIN-1) serves as a ubiquitin sensor and autophagy receptor, crucial for modulating inflammation and cell death. Our previous in vitro investigation identified the LC3-interacting region (LIR) motifs 1 and 2 of ABIN-1 as key mitophagy regulators. This study aimed to explore the in vivo biological significance of ABIN1-LIR domains using a novel CRISPR-engineered ABIN1-ΔLIR1/2 mouse model, which lacks both LIR motifs.
View Article and Find Full Text PDFFront Oncol
August 2025
Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, China.
Introduction: Pancreatic adenocarcinoma (PAAD) is a highly aggressive malignancy characterized by a profoundly hypoxic tumor microenvironment, which fosters tumor progression and confers resistance to therapy The oncogenic regulator ID1has been implicated in PAAD malignancy, however, the mechanisms underlying hypoxia-induced stabilization of ID1 and the role of ubiquitin-mediated degradation remain poorly understood. Elucidating these pathways is essential for identifying novel therapeutic targets for PAAD.
Methods: In this study, we examined ID1 expression in PAAD tissues and cell lines using publicly available databases and in vitro models.