Deoxycytidine kinase (dCK) activates several antileukaemic nucleoside analogues. We have recently reported that the activity of dCK, overexpressed in HEK 293T cells, correlates with its phosphorylation level on Ser-74. Here, we show that dCK from B-cell chronic lymphocytic leukaemia (B-CLL) lymphocytes can be detected by an anti-phospho-Ser-74 antibody and that interindividual variability in dCK activity is related to its phosphorylation level on Ser-74. Moreover, pharmacological intervention modified Ser-74 phosphorylation, in close parallel with changes in dCK activity. These results suggest that activation of dCK via phosphorylation of Ser-74 might constitute a new therapeutic strategy to enhance activation and efficacy of nucleoside analogues.
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http://dx.doi.org/10.1016/j.canlet.2007.01.013 | DOI Listing |
Immunology
February 2025
Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, California, USA.
Autoreactive, aberrantly activated lymphocytes that target myelin antigens in the central nervous system (CNS) are primary drivers of the autoimmune disease multiple sclerosis (MS). Proliferating cells including activated lymphocytes require deoxyribonucleoside triphosphates (dNTPs) for DNA replication. dNTPs can be synthesised via the de novo pathway from precursors such as glucose and amino acids or the deoxyribonucleoside salvage pathway from extracellular deoxyribonucleosides.
View Article and Find Full Text PDFClin Exp Immunol
December 2024
Clinical Board Medicine (Neuroscience), The Royal London Hospital, Barts Health NHS Trust, London, UK.
Introduction: Cladribine is a deoxyadenosine analogue that can penetrate the blood-brain barrier. It is used to treat multiple sclerosis (MS). However, the mechanistic understanding of the effect of this highly effective therapy on B cells and plasma cells in the central nervous system compartment is limited.
View Article and Find Full Text PDFAnticancer Res
December 2024
Center for Translational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand;
Background/aim: Chemotherapy resistance is an important problem in the treatment of patients with cholangiocarcinoma (CCA) who are not eligible for surgery. This study aimed to overcome gemcitabine (Gem) resistance in CCA by investigating and targeting Gem resistance-associated molecules.
Materials And Methods: Three stable Gem-resistant CCA cell lines (CCA-GemR) were established by gradually exposing CCA cell lines to Gem.
J Dermatol Sci
November 2024
Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Institute on Aging, Seoul National University, Seoul, Republic of Korea. Electronic address:
Background: Overexposure to ultraviolet (UV) radiation accelerates skin aging, resulting in wrinkle formation, reduced skin elasticity, and hyperpigmentation. UV irradiation induces increased matrix metalloproteinases (MMPs) that degrade collagen in the extracellular matrix. Skin aging is also accompanied by epigenetic alterations such as promoter methylation by DNA methyltransferases, leading to the activation or suppression of gene expression.
View Article and Find Full Text PDFNucleosides Nucleotides Nucleic Acids
October 2024
Department of Pharmacology, College of Pharmacy, King Khalid University, Abha, Saudi Arabia.
The development of alternative anticancer agents with minimal side effects has become more critical due to the rising recurrence of mammalian malignancies and the severe side effects of chemotherapeutic treatments. Kinases are an essential target for neostatic impact as they play an important role in the modulation of growth factor signalling. Our work aims to screen novel nine-series of thiazole-based aminopyrimidines and sulphaminopyrimidines against the enzymes mitochondrial thymidine kinase 2, deoxyguanosine kinase (2OCP), deoxycytidine kinase (2QRN) and thymidylate kinase (1E2Q) by molecular docking, synthesise and to study their in vitro inhibitory studies.
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