During immunoglobulin class-switch recombination (CSR), the cytidine deaminase AID induces double-strand breaks into transcribed, repetitive DNA elements called switch sequences. The mechanism that promotes the binding of AID specifically to switch regions remains to be elucidated. Here we used a proteomic screen with in vivo biotinylation of AID to identify the splicing regulator PTBP2 as a protein that interacts with AID. Knockdown of PTBP2 mediated by short hairpin RNA in B cells led to a decrease in binding of AID to transcribed switch regions, which resulted in considerable impairment of CSR. PTBP2 is thus an effector of CSR that promotes the binding of AID to switch-region DNA.
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http://dx.doi.org/10.1038/ni.1977 | DOI Listing |
Mol Ther Methods Clin Dev
March 2025
Department of Medicine, Division of Infectious Diseases, Mayo Clinic, Rochester, MN 55902, USA.
Lipid nanoparticles (LNPs) are often liver tropic, presenting challenges for LNP-delivered mRNA therapeutics intended for other tissues, as off-target expression in the liver may increase side effects and modulate immune responses. To avoid off-target expression in the liver, miR-122 binding sites have been used by others in viral and non-viral therapeutics. Here, we use a luciferase reporter system to compare different copy numbers and insertion locations of miR-122 binding sequences to restrict liver expression.
View Article and Find Full Text PDFCurr Res Struct Biol
June 2025
Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jalan Raya Bandung-Sumedang KM 21, Sumedang, 45363, Indonesia.
Cinnamomum, a genus within the Lauraceae family, has gained global recognition due to its wide-ranging utility. Extensive research has been dedicated to exploring its phytochemical composition and pharmacological effects. Notably, the uniqueness of Cinnamomum lies in its terpenoid content, characterized by distinctive structures and significant biological implications.
View Article and Find Full Text PDFFEBS Lett
January 2025
PHYLIFE, Physical Life Science, Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense, Denmark.
5HTR is a G-protein-coupled receptor that drives many neuronal functions and is a target for psychedelic drugs. Understanding ligand interactions and conformational transitions is essential for developing effective pharmaceuticals, but mechanistic details of 5HTR activation remain poorly understood. We utilized all-atom molecular dynamics simulations and free-energy calculations to investigate 5HTR's conformational dynamics upon binding to serotonin and psilocin.
View Article and Find Full Text PDFCell Signal
January 2025
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430079, China. Electronic address:
Fractures are common and serious skeletal injuries, and accelerating their healing while alleviating patient suffering remains a clinical challenge. Annexin A2 (ANXA2) is a widely distributed, calcium-dependent, phospholipid-binding protein involved in bone remodeling. However, its role in chondrocyte differentiation and endochondral ossification remains unclear.
View Article and Find Full Text PDFMolecules
January 2025
Cancer Microenvironment Branch, Division of Cancer Biology, Research Institute, National Cancer Center, Goyang-si 10408, Republic of Korea.
As a scaffolding protein, Raf kinase binding protein (RKIP) is involved in a variety of cellular pathways, including the Raf-MEK-ERK-cascade. It acts as a negative regulator by binding to its partners, making it an attractive target in the development of therapeutic strategies for cancer. Despite its structural stability as a monomer, RKIP may form a dimer, resulting in the switching of binding partners.
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