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Cytidine/Uridine monophosphate kinase 2 (CMPK2) is a crucial enzyme responsible for the phosphorylation of nucleotides, specifically converting cytidine monophosphate (CMP) and uridine monophosphate (UMP) into their respective diphosphates, known as cytidine diphosphate (CDP) and uridine diphosphate (UDP). Recent studies have demonstrated that CMPK2 plays a pivotal role in multiple pathophysiological processes, such as cellular nucleotide metabolism, energy homeostasis, and inflammatory response. Dysregulation of CMPK2 has been implicated in a variety of pathologies, including viral infections, neurodegenerative diseases, and autoimmune disorders. Despite its biological significance and interventive potential, knowledge gaps remain with respect to CMPK2, in particular, the precise molecular mechanism and mechanical basis through which it contributes to the onset and progression of underlying diseases. In this regard, this narrative review aims to provide an overview concerning the biological functions of CMPK2, shed light on its involvement in disease pathogenesis alongside clinical relevance, and ultimately highlight potential therapeutic strategies to target CMPK2 across multisystemic disorders.
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http://dx.doi.org/10.1186/s13578-025-01466-y | DOI Listing |
J Am Soc Nephrol
September 2025
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
Background: Genetic modifiers are believed to play an important role in the onset and severity of polycystic kidney disease (PKD), but identifying these modifiers has been challenging due to the lack of effective methodologies.
Methods: We generated zebrafish mutants of IFT140, a skeletal ciliopathy gene and newly identified autosomal dominant PKD (ADPKD) gene, to examine skeletal development and kidney cyst formation in larval and juvenile mutants. Additionally, we utilized ift140 crispants, generated through efficient microhomology-mediated end joining (MMEJ)-based genome editing, to compare phenotypes with mutants and conduct a pilot genetic modifier screen.
JCI Insight
September 2025
Department of Pharmacology, University of Michigan, Ann Arbor, United States of America.
Cardiac hypertrophy is a common adaptation to cardiovascular stress and often a prelude to heart failure. We examined how S-palmitoylation of the small GTPase, Ras-related C3 botulinum toxin substrate 1 (Rac1), impacts cardiomyocyte stress signaling. Mutation of the cysteine-178 palmitoylation site impaired activation of Rac1 when overexpressed in cardiomyocytes.
View Article and Find Full Text PDFJ Clin Invest
September 2025
The University of Texas at Austin, Austin, United States of America.
Background: Following SARS-CoV-2 infection, ~10-35% of COVID-19 patients experience long COVID (LC), in which debilitating symptoms persist for at least three months. Elucidating biologic underpinnings of LC could identify therapeutic opportunities.
Methods: We utilized machine learning methods on biologic analytes provided over 12-months after hospital discharge from >500 COVID-19 patients in the IMPACC cohort to identify a multi-omics "recovery factor", trained on patient-reported physical function survey scores.
JCI Insight
September 2025
Diabetes & Metabolism Research Center, University of Utah, Salt Lake City, United States of America.
Impaired muscle regrowth in aging is underpinned by reduced pro-inflammatory macrophage function and subsequently impaired muscle cellular remodeling. Macrophage phenotype is metabolically controlled through TCA intermediate accumulation and activation of HIF1A. We hypothesized that transient hypoxia following disuse in old mice would enhance macrophage metabolic inflammatory function thereby improving muscle cellular remodeling and recovery.
View Article and Find Full Text PDFJ Clin Invest
September 2025
Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America.
3-O-sulfation of heparan sulfate (HS) is the key determinant for binding and activation of Antithrombin III (AT). This interaction is the basis of heparin treatment to prevent thrombotic events and excess coagulation. Antithrombin-binding HS (HSAT) is expressed in human tissues, but is thought to be expressed in the subendothelial space, mast cells, and follicular fluid.
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