Four adjacent genes (sipW, sipX, sipY and sipZ) encoding different type I signal peptidases, were isolated on a 7860 bp DNA fragment from Streptomyces lividans TK21. Three of the sip genes constitute an operon and the fourth is the first gene of another operon encompassing three additional, unrelated genes. A DNA fragment containing the four sip genes complemented an Escherichia coli type I signal peptidase mutant when cloned in a multicopy plasmid. Clustering of four different type I signal peptidase genes seems, so far, to be a unique feature of Streptomyces.
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http://dx.doi.org/10.1099/00221287-145-9-2255 | DOI Listing |
J Med Chem
January 2025
Insilico Medicine Shanghai Ltd, Suite 901, Tower C, Changtai Plaza, 2889 Jinke Road, Pudong New District, Shanghai 201203, China.
Protein arginine methyltransferase 5 (PRMT5), which catalyzes the symmetric dimethylation of arginine residues on target proteins, plays a critical role in gene expression regulation, RNA processing, and signal transduction. Aberrant PRMT5 activity has been implicated in cancers and other diseases, making it a potential therapeutic target. Here, we report the discovery of a methylthioadenosine (MTA) cooperative PRMT5 inhibitor.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Key Laboratory of Molecular Nanostructure and Nanotechnology, Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
Emerging evidence indicates that intratumor bacteria exist as an active and specific tumor component in many tumor types beyond digestive and respiratory tumors. However, the biological impact and responsible molecules of such local bacteria-tumor direct interaction on cancer therapeutic response remain poorly understood. Trastuzumab is among the most commonly used drugs targeting the receptor tyrosine-protein kinase erbB-2 (ErbB2) in breast cancer, but its resistance is inevitable, severely limiting its clinical effectiveness.
View Article and Find Full Text PDFAllergol Immunopathol (Madr)
January 2025
Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran;
Common variable immunodeficiency (CVID) is the most common symptomatic and heterogeneous type of inborn errors of immunity (IEI). However, the pathogenesis process of this disease is often unknown. Epigenetic modifications may be involved in unresolved patients.
View Article and Find Full Text PDFJ Proteome Res
January 2025
Department of Plant Biotechnology and Bioinformatics, Ghent University, 9052 Ghent, Belgium.
Proteomics has become a powerful approach for the identification and characterization of type III effectors (T3Es). Members of the species complex (RSSC) deploy T3Es to manipulate host cells and to promote root infection of, among others, a wide range of solanaceous plants such as tomato, potato, and tobacco. Here, we used TurboID-mediated proximity labeling (PL) in tomato hairy root cultures to explore the proxeomes of the core RSSC T3Es RipU, RipD, and RipB.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Background: The nuclear clearance and cytoplasmic aggregation of splicing repressor TAR DNA/RNA-binding protein-43 (TDP-43) occur in approximately 50% of Alzheimer's disease (AD) cases and about 45% of frontotemporal dementia (FTD). However, it is not clear how early such mechanism occurs in AD and FTD as there is no method of detecting TDP-43 dysregulation in living individuals. Since the loss of nuclear TDP-43 leads to cryptic exon inclusion, we propose that cryptic exon-encoded peptides may be detected in patient biofluids as biomarkers of TDP-43 loss of function.
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