5'-Amino-5'-deoxythymidine (5'-AdThd) was found to antagonize the feedback inhibition exerted by dTTP on dThd kinase (EC 2.7.1.21). This effect was demonstrable in intact cells, cellular extracts, and purified enzyme preparations. Thus, 5'-AdThd markedly stimulated the uptake of dThd in Hela and Vero cells and reduced the inhibitory effects of dTTP on the dThd kinase activity measured in extracts from both cell types. dThd kinase was purified by affinity column chromatography from Hela and Vero cells, and 5'-AdThd was again shown to reduce the inhibition caused by dTTP. The ability of 5'-AdThd to disrupt the homeostatic mechanisms normally regulating the uptake of dThd was sufficient to convert a noncytotoxic concentration of dThd (30 microM) to one that inhibited Hela cell growth by 40%. Since the activity of regulatory enzymes critically influences the pharmacological response produced by many agents, we propose the design of compounds specifically targeted at enzyme regulatory sites as an approach to drug development.
Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
ERK-USP9X-coupled regulation of thymidine kinase 1 promotes both its enzyme activity-dependent and its enzyme activity-independent functions for tumor growth.
Nat Struct Mol Biol
January 2025
Zhejiang Provincial Key Laboratory of Pancreatic Disease, Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Thymidine kinase 1 (TK1), a crucial enzyme in DNA synthesis, is highly expressed in various cancers. However, the mechanisms underlying its elevated expression and the implications for tumor metabolism remain unclear. Here we demonstrate that activation of growth factor receptors enhances TK1 expression.
View Article and Find Full Text PDFIdentification of pyrimidine metabolism-based molecular subtypes and prognostic signature to predict immune landscape and guide clinical treatment in prostate cancer.
Ann Med
December 2025
Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
Background: We previously described the enrichment of plasma exosome metabolites in CRPC, PCa, and TFC cohorts, and found significant differences in pyrimidine metabolites. The PMGs is associated with the clinical prognosis of several cancers, but its biological role in PCa is still unclear.
Methods: This study extracted 98 reliable PMGs, and analyzed their somatic mutations, expression levels, and prognostic significance.
Thymidine Analogue Mutations with M184V Significantly Decrease Phenotypic Susceptibility of HIV-1 Subtype C Reverse Transcriptase to Islatravir.
Viruses
December 2024
HIV Pathogenesis Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa.
Islatravir (ISL) is the first-in-class nucleoside reverse transcriptase translocation inhibitor (NRTtI) with novel modes of action. Data on ISL resistance are currently limited, particularly to HIV-1 non-B subtypes. This study aimed to assess prevalent nucleos(t)ide reverse transcriptase inhibitor (NRTI)-resistant mutations in HIV-1 subtype C for their phenotypic resistance to ISL.
View Article and Find Full Text PDFA Mutation in the Herpes Simplex Virus Type 1 (HSV-1) UL29 Gene is Associated with Anti-Herpesvirus Drugs' Susceptibility.
Viruses
November 2024
Department of Virology 1, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
Herpes simplex virus type 1 (HSV-1) acyclovir (ACV) resistance is acquired by mutations in the viral thymidine kinase (TK) or DNA polymerase (DNApol) genes. We previously obtained an ACV-resistant clone (HSV-1_VZV_TK_clone α) by sequential passages of HSV-1_VZV-TK, a recombinant virus which lacked its endogenous TK activity and instead expressed the varicella-zoster virus (VZV) TK ectopically. HSV-1_VZV_TK_clone α had been generated using an HSV-1_BAC in the presence of increasing concentrations of ACV.
View Article and Find Full Text PDFPredicting the Invasiveness of Mixed Ground-Glass Nodules Based on Spectral Computed Tomography-Derived Parameters and Tumor Abnormal Protein Levels: Development and Validation of a Model.
Acad Radiol
January 2025
Department of Radiology, Shengjing Hospital of China Medical University, China (Y.Y., T.W.). Electronic address:
Rationale And Objectives: Mixed ground-glass nodules (mGGNs) are highly malignant and common nonspecific lung imaging findings. This study aimed to explore whether combining quantitative and qualitative spectral dual-layer detector-based computed tomography (SDCT)-derived parameters with serological tumor abnormal proteins (TAPs) and thymidine kinase 1 (TK1) expression enhances invasive mGGN diagnostic efficacy and to develop a joint diagnostic model.
Materials And Methods: This prospective study included patients with mGGNs undergoing preoperative triple-phase contrast-enhanced SDCT with TAP and TK1 tests.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!