S-adenosylmethionine is a metabolite regulating many biological processes; S-adenosylmethionine effect on ubiquitin-proteasome system (UPS) has not been studied yet. We investigated S-adenosylmethionine effects on UPS activity both in vitro, by inhibitor screening assay, and in rat vascular smooth muscle cells, by Western Blot of proteasomal targets. We found that S-adenosylmethionine inhibited UPS activity.
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http://dx.doi.org/10.2174/092986608783330396 | DOI Listing |
Acta Pharm Sin B
December 2024
School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.
The fat mass and obesity-associated protein (FTO) is an RNA demethylase required for catalytic demethylation of -methyladenosine (mA); it is highly expressed and functions as an oncogene in acute myeloid leukemia (AML). Currently, the overarching objective of targeting FTO is to precisely inhibit the catalytic activity. Meanwhile, whether FTO degradation also exerts antileukemic effects remains unknown.
View Article and Find Full Text PDFJ Adv Res
January 2025
College of Animal Science and Technology, Nanjing Agricultural University, Weigang 1, Nanjing 210095, China. Electronic address:
Introduction: Hypoxia, a condition characterized by inadequate oxygen supply to tissues, triggers various cellular responses, including apoptosis. The RNA demethylase FTO has been shown to exert anti-apoptotic effects, but its functions independent of RNA demethylase-particularly those involving protein-protein interactions-during hypoxia remain unclear.
Objectives: This study aimed to elucidate the cytoprotective mechanism of FTO in preventing apoptosis under hypoxic stress.
Biomol Biomed
January 2025
Department of Critical Care Medicine, Affiliated Hospital of Nantong University, Medical school of Nantong University, Jiangsu, China.
Sepsis-induced myocardial dysfunction (SIMD) is a severe complication of sepsis, characterized by impaired cardiac function and high mortality rates. Despite significant advances in understanding sepsis pathophysiology, the molecular mechanisms underlying SIMD remain incompletely elucidated. Ubiquitination and deubiquitination, critical post-translational modifications (PTMs) regulating protein stability, localization, and activity, play pivotal roles in cellular processes, such as inflammation, apoptosis, mitochondrial function, and calcium handling.
View Article and Find Full Text PDFJ Mol Cell Cardiol Plus
March 2024
Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
Sacubitril/valsartan (Sac/Val) belongs to the group of angiotensin receptor-neprilysin inhibitors and has been used for the treatment of heart failure (HF) for several years. The mechanisms that mediate the beneficial effects of Sac/Val are not yet fully understood. In this study we investigated whether Sac/Val influences the two proteolytic systems, the ubiquitin-proteasome system (UPS) and the autophagy-lysosomal pathway (ALP), in a mouse model of pressure overload induced by transverse aortic constriction (TAC) and in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) treated with endothelin-1 (ET1) serving as a human cellular model of hypertrophy.
View Article and Find Full Text PDFCell Mol Life Sci
January 2025
State Key Laboratory of Molecular Medicine and Biological Diagnosis and Treatment (Ministry of Industry and Information Technology), Aerospace Center Hospital, School of Life Science, Beijing Institute of Technology, Beijing, 100081, China.
Uncontrollable cancer cell growth is characterized by the maintenance of cellular homeostasis through the continuous accumulation of misfolded proteins and damaged organelles. This review delineates the roles of two complementary and synergistic degradation systems, the ubiquitin-proteasome system (UPS) and the autophagy-lysosome system, in the degradation of misfolded proteins and damaged organelles for intracellular recycling. We emphasize the interconnected decision-making processes of degradation systems in maintaining cellular homeostasis, such as the biophysical state of substrates, receptor oligomerization potentials (e.
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