Plants have evolved an intricate regulatory network of proteases and corresponding protease inhibitors (PI), which operate in various biological pathways and serve diverse spatiotemporal functions during the sedentary life of a plant. Intricacy of the regulatory network can be anticipated from the observation that, depending on the developmental stage and environmental cue(s), either a single PI or multiple PIs regulate the activity of a given protease. On the other hand, the same PI often interacts with different targets at different places, necessitating another level of fine control to be added in planta. Here, it is reported on how the activity of a papain-like cysteine protease dubbed RD21 (RESPONSIVE TO DESICCATION 21) is differentially regulated by serpin and Kunitz PIs over plant development and how this mechanism contributes to defenses against herbivorous arthropods and microbial pests.
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http://dx.doi.org/10.1080/19420889.2017.1368599 | DOI Listing |
J Proteome Res
January 2025
Target Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7FZ, U.K.
Inhibition of the mitochondrial deubiquitinating (DUB) enzyme USP30 is neuroprotective and presents therapeutic opportunities for the treatment of idiopathic Parkinson's disease and mitophagy-related disorders. We integrated structural and quantitative proteomics with biochemical assays to decipher the mode of action of covalent USP30 inhibition by a small-molecule containing a cyanopyrrolidine reactive group, . The inhibitor demonstrated high potency and selectivity for endogenous USP30 in neuroblastoma cells.
View Article and Find Full Text PDFArch Dermatol Res
January 2025
Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, 1150 NW 14th Street, Miami, FL, 33136, USA.
Pityriasis rosea (PR) is an acute exanthematous disease with an uncertain physiopathology, increasingly recognized as potentially drug induced. This study aims to investigate medication triggers associated with PR by analyzing cases reported in the FDA Adverse Event Reporting System (FAERS) database. A retrospective review of 343 PR cases reported in the FAERS database from January 1, 1998, to March 31, 2024, was conducted.
View Article and Find Full Text PDFPediatr Allergy Immunol
January 2025
Department of Microbiology, Immunology and Transplantation, Allergy and Immunology Research Group, KU Leuven, Leuven, Belgium.
Background: Type 1 regulatory T (Tr1) cells are critical players in maintaining peripheral tolerance, by producing high IL-10 levels in association with inducible T-cell co-stimulator (ICOS) expression. Whether these cells play a role in naturally acquired baked egg tolerance is unknown.
Objectives: Evaluate frequencies of egg-responsive Tr1 and Th2 cells in egg-allergic children that naturally acquired baked egg tolerance (BET) versus non-egg-allergic (NEA) children.
Biotechnol Bioeng
January 2025
Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
Human pluripotent stem cells (hPSCs) can be differentiated in vitro to an increasing number of mature cell types, presenting significant promise for addressing a wide range of diseases and studying human development. One approach to further enhance stem cell differentiation methods would be to coordinate multiple inducible gene or protein switches to operate simultaneously within the same cell, with minimal cross-interference, to precisely regulate a network of lineage-specifying transcription factors (TFs) to guide cell fate decisions. Therefore, in this study, we designed and tested various mammalian gene and protein switches responsive to clinically safe small-molecule inhibitors of viral proteases.
View Article and Find Full Text PDFCancer Discov
January 2025
School of Medicine, University of Leeds, Leeds, United Kingdom.
Priego and colleagues identify a secreted glycoprotein TIMP1, expressed downstream of the transcription factor STAT3, in a subpopulation of STAT3+ reactive astrocytes as a mediator of immunosuppression in late-stage brain metastases. The STAT3 inhibitor silibinin enhances the preclinical efficacy of the combined PD-1/CTLA4 immune checkpoint blockade, providing a rationale to translate the combination therapy into clinical use for this underserved patient group with poor prognosis. See related article by Priego et al.
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