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To efficiently counteract pathogens, plants rely on a complex set of immune responses that are tightly regulated to allow the timely activation, appropriate duration and adequate amplitude of defense programs. The coordination of the plant immune response is known to require the activity of the ubiquitin/proteasome system, which controls the stability of proteins in eukaryotes. Here, we demonstrate that the N-end rule pathway, a subset of the ubiquitin/proteasome system, regulates the defense against a wide range of bacterial and fungal pathogens in the model plant Arabidopsis thaliana. We show that this pathway positively regulates the biosynthesis of plant-defense metabolites such as glucosinolates, as well as the biosynthesis and response to the phytohormone jasmonic acid, which plays a key role in plant immunity. Our results also suggest that the arginylation branch of the N-end rule pathway regulates the timing and amplitude of the defense program against the model pathogen Pseudomonas syringae AvrRpm1.
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http://dx.doi.org/10.1038/srep26020 | DOI Listing |
Protein Sci
August 2025
Division of Surgical Sciences, Moores Cancer Center, University of California, San Diego, La Jolla, California, USA.
The UBR family of ubiquitin ligases binds to N-termini of their targets (known as N-degron) to induce their ubiquitination and degradation via a conserved domain known as UBR-box. UBR1 and UBR2 share the highest sequence homology among the family, and substantial structural studies were previously performed for substrate binding by the UBR-boxes of UBR1 and UBR2. Here, we describe a new pocket in the UBR-boxes of UBR1 and UBR2 for binding the second residues of N-degrons through determining five co-crystal structures of the UBR-boxes with various N-degron peptides.
View Article and Find Full Text PDFPharmaceutics
August 2025
Division of Magnetic Resonance, Korea Basic Science Institute (KBSI), Ochang, Cheongju 28119, Republic of Korea.
: Cervical cancer remains a major global health concern, with existing chemotherapy facing limited effectiveness owing to resistance. Polo-like kinase 1 (PLK1) overexpression in cervical cancer cells is a promising target for developing novel therapies to overcome chemoresistance and improve treatment efficacy. : In this study, we developed a novel PROTAC, NC1, targeting PLK1 PBD via the N-end rule pathway.
View Article and Find Full Text PDFCell Death Dis
August 2025
Department of Molecular & Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL, USA.
Cell death regulation is essential for stress adaptation and/or signal response. Past studies have shown that eukaryotic cell death is mediated by an evolutionarily conserved enzyme, arginyltransferase1 (Ate1). The downregulation of Ate1, as seen in many types of cancer, prominently increases cellular tolerance to a variety of stress conditions.
View Article and Find Full Text PDFYeast
July 2025
ARC Centre of Excellence in Synthetic Biology, Sydney, New South Wales, Australia.
Dynamic downregulation of the endogenous farnesyl pyrophosphate (FPP) synthase (Erg20p) is crucial to engineer heterologous monoterpene production in the yeast Saccharomyces cerevisiae. FPP downstream metabolite geranylgeranyl pyrophosphate (GGPP) can induce the degradation of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase 2 (Hmg2p) through its N-terminal GGPP-sensing endoplasmic reticulum transmembrane domain (Hmg2p) in S. cerevisiae.
View Article and Find Full Text PDFJ Biol Chem
August 2025
Department of Biochemistry, SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology, Shenzhen, China; Key University Laboratory of Metabolism and Health of Guangdong, Southern University of Science and Technology, Shenzhen, China. Electronic address:
Parkinson's disease (PD), the second most prevalent neurodegenerative disorder, is associated with α-synuclein (α-syn) overexpression or mutation, leading to harmful aggregates and neuronal apoptosis. Effective drugs that inhibit or reduce α-syn accumulation remain challenging. Targeted protein degradation (TPD) technology offers a novel solution by utilizing the ubiquitin-proteasome pathway to target specific proteins for destruction.
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