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http://dx.doi.org/10.1016/j.jacbts.2021.10.015 | DOI Listing |
The Rac1 P29S hotspot mutation in cutaneous melanoma is associated with resistance to MAPK pathway inhibitors (MAPKi) and worse clinical outcomes. Moreover, activation of Rac1 guanine exchange factors (GEFs) also promotes MAPKi-resistance, particularly in undifferentiated melanoma cells. Here we delineate mechanisms of Rac1-driven MAPKi-resistance and identify strategies to inhibit the growth of this class of cutaneous melanomas.
View Article and Find Full Text PDFUnlabelled: Pre-mRNA splicing, carried out in the nucleus by a large ribonucleoprotein machine known as the spliceosome, is functionally and physically coupled to the mRNA surveillance pathway in the cytoplasm called nonsense mediated mRNA decay (NMD). The NMD pathway monitors for premature translation termination signals, which can result from alternative splicing, by relying on the exon junction complex (EJC) deposited on exon-exon junctions by the spliceosome. Recently, multiple genetic screens in human cell lines have identified numerous spliceosome components as putative NMD factors.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Biology, Institute of Genetics, The Faculty of Mathematics and Natural Sciences, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Female reproduction comes at great expense to energy metabolism compensated by extensive organ adaptations including intestinal size. Upon mating, endocrine signals orchestrate a 30% net increase of absorptive epithelium. Mating increases production of the steroid hormone Ecdysone released by the Drosophila ovaries that stimulates intestinal stem cell (ISC) divisions.
View Article and Find Full Text PDFCancer Metastasis Rev
January 2025
Department of Biochemistry and Molecular and Cellular Biology, Georgetown University Medical Center, BSB 231A, 3900 Reservoir Rd., NW, Washington, DC, 20057, USA.
Neuropeptide Y (NPY) is a sympathetic neurotransmitter widely distributed in the peripheral and central nervous system, affecting many physiological functions. Consequently, dysregulation of the NPY system contributes to numerous pathological disorders, including stress, obesity, and cancer. The pleiotropic functions of NPY in humans are mediated by G protein-coupled receptors (Y1R, Y2R, Y5R), which activate several signaling pathways and thereby regulate cell growth, differentiation, apoptosis, proliferation, angiogenesis, and metabolism.
View Article and Find Full Text PDFFront Pharmacol
December 2024
Department of Hygiene, Epidemiology and Ergonomics, Medical University of Bialystok, Bialystok, Poland.
The growing burden of metabolic disorders manifested by hypertension, type 2 diabetes mellitus, hyperlipidemia, obesity and non-alcoholic fatty liver disease presents a significant global health challenge by contributing to cardiovascular diseases and high mortality rates. Β-blockers are among the most widely used drugs in the treatment of hypertension and acute cardiovascular events. In addition to blocking the receptor sites for catecholamines, third-generation β-blockers with associated vasodilating properties, such as carvedilol and nebivolol, provide a broad spectrum of metabolic effects, including anti-inflammatory and antioxidant properties and a favorable impact on glucose and lipid metabolism.
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