The emerging proteolysis targeting antibodies (PROTABs) offer an attractive technology that circumvents some of the challenges of small-molecule intracellular degraders with limited bioavailability and cell permeability. PROTABs present an improved approach to target degradation of membrane-bound and cell surface proteins and use multispecific binding proteins such as multispecific antibodies that bind to at least one transmembrane E3 ubiquitin ligase as well as cell surface proteins intended for degradation.
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http://dx.doi.org/10.1021/acsmedchemlett.2c00458 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Department of Medical Neuroscience, SUSTech Center for Pain Medicine, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China.
Ubiquitin-proteasomal degradation of K/Cl cotransporter 2 (KCC2) in the ventral posteromedial nucleus (VPM) has been demonstrated to serve as a common mechanism by which the brain emerges from anesthesia and regains consciousness. Ubiquitin-proteasomal degradation of KCC2 during anesthesia is driven by E3 ligase Fbxl4. However, the mechanism by which ubiquitinated KCC2 is targeted to the proteasome has not been elucidated.
View Article and Find Full Text PDFAnticancer Agents Med Chem
January 2025
Department of Chemistry, Illinois State University, Normal, Il, USA.
Many oncoproteins are important therapeutic targets because of their critical role in inducing rapid cell proliferation, which represents one of the salient hallmarks of cancer. Chronic Myeloid Leukemia (CML) is a cancer of hematopoietic stem cells that is caused by the oncogene BCR-ABL1. BCR-ABL1 encodes a constitutively active tyrosine kinase protein that leads to the uncontrolled proliferation of myeloid cells, which is a hallmark of CML.
View Article and Find Full Text PDFCurr Microbiol
January 2025
Department of Microbiology and Immunology, School of Medicine, Soonchunhyang University, Cheonan-si, Chungnam, 31151, Republic of Korea.
Lactic acid bacteria (LAB), traditionally consumed as fermented foods, are now being applied to the medical field beyond health-functional food as probiotics. Therefore, it is necessary to continuously discover and evaluate new strains with suitable probiotic characteristics, mainly focusing on safety. In this study, we isolated eight new strains from postmenopausal vaginal fluid using culturomics approaches, an emerging area of interest.
View Article and Find Full Text PDFCurr Opin Obstet Gynecol
December 2024
Mount Sinai Medical Center, Miami Beach, Florida, USA.
Purpose Of Review: Endometrial cancer (EC) is rising in incidence, particularly in younger, premenopausal women, due to increasing rates of obesity and delayed childbearing. This review evaluates current and emerging endocrine therapies, with a focus on fertility-preserving approaches for early-stage EC and treatment options for advanced or recurrent disease.
Recent Findings: Fertility-sparing endocrine therapies, such as medroxyprogesterone acetate, megestrol acetate, and levonorgestrel-releasing intrauterine devices, achieve high response rates but carry recurrence risks.
Elife
January 2025
Department of Chemistry & Biochemistry, University of Delaware, Newark, United States.
The SARS-CoV-2 main protease (M or Nsp5) is critical for production of viral proteins during infection and, like many viral proteases, also targets host proteins to subvert their cellular functions. Here, we show that the human tRNA methyltransferase TRMT1 is recognized and cleaved by SARS-CoV-2 M. TRMT1 installs the ,-dimethylguanosine (m2,2G) modification on mammalian tRNAs, which promotes cellular protein synthesis and redox homeostasis.
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