AI Article Synopsis
Article Abstract
The histidine triad nucleotide binding protein 1 (HINT1) is a nucleoside phosphoramidase that has garnered interest due to its widespread expression and participation in a broad range of biological processes. Herein, we discuss the role of HINT1 as a regulator of several CNS functions, tumor suppressor, and mast cell activator via its interactions with multiple G-protein-coupled receptors and transcription factors. Importantly, altered HINT1 expression and mutation are connected to the progression of multiple disease states, including several neuropsychiatric disorders, peripheral neuropathy, and tumorigenesis. Additionally, due to its involvement in the activation of several clinically used phosphoramidate prodrugs, tremendous efforts have been made to better understand the interactions behind nucleoside binding and phosphoramidate hydrolysis by HINT1. We detail the substrate specificity and catalytic mechanism of HINT1 hydrolysis, while highlighting the structural biology behind these efforts. The aim of this review is to summarize the multitude of biological and pharmacological functions in which HINT1 participates while addressing the areas of need for future research.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10580397 | PMC |
| http://dx.doi.org/10.1021/acsptsci.3c00079 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Effect of CXCR2 Deficiency in HeLa Cell on the Regulatory Network of Coding Genes and Non-Coding RNAs.
Ann Clin Lab Sci
November 2024
Department of Laboratory Medicine, Linyi People's Hospital, Linyi, Shandong, China
Objective: C-X-C motif chemokine receptor 2 (CXCR2) plays a crucial role in inflammation and immunity, and the involvement of chemokine receptors in the tumor microenvironment is extensively documented. However, the impact of CXCR2 deficiency on the complete transcriptome, including mRNA and ncRNAs, in tumor cells remains unclear.
Methods: In this study, we aimed to identify differentially expressed (DE) messenger RNA (mRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in CXCR2 knockout HeLa cells through transcriptome sequencing and to construct regulatory networks.
Genetic and pharmacological targeting of HINT2 promotes OXPHOS to alleviate inflammatory responses and cell necrosis in acute pancreatitis.
Pharmacol Res
January 2025
Department of Integrated Traditional Chinese and Western Medicine, West China Hospital of Sichuan University, Chengdu, China. Electronic address:
The necrosis of pancreatic acinar cells is a key molecular event in the progression of acute pancreatitis (AP), with disturbances in mitochondrial energy metabolism considered to be a direct causative factor of acinar cell necrosis. Histidine triad nucleotide-binding protein 2 (HINT2) has been implicated in the development of various diseases, whereas its involvement in the progression of AP remains unclear. This study aims to investigate the role of HINT2 in AP.
View Article and Find Full Text PDFCryo-EM structure of an activated GPR4-Gs signaling complex.
Nat Commun
January 2025
Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Article Synopsis
- G protein-coupled receptor 4 (GPR4) is part of a group called proton-sensing GPCRs that respond to pH changes and regulate various physiological functions, with its overactivation noted in acidic tumor environments.
- Researchers used cryo-electron microscopy to determine the 3D structures of zebrafish GPR4 at different pH levels, revealing important histidine and acidic residues that affect its proton-sensing ability, alongside key triad residues.
- The study also identified a cluster of aromatic residues in GPR4's orthosteric pocket that may play a crucial role in transferring signals to the inside of the cell, laying the groundwork for further research on psGPCRs.
LRP1 involvement in FHIT-regulated HER2 signaling in non-small cell lung cancer.
Eur J Cell Biol
March 2025
Université de Reims Champagne-Ardenne, INSERM, P3Cell, UMR-S 1250, Reims, France. Electronic address:
The tumor suppressor fragile histidine triad (FHIT) is frequently lost in non-small cell lung cancer (NSCLC). We previously showed that a down-regulation of FHIT causes an up-regulation of the activity of HER2 associated to an epithelial-mesenchymal transition (EMT) and that lung tumor cells harboring a FHIT/pHER2 phenotype are sensitive to anti-HER2 drugs. Here, we sought to decipher the FHIT-regulated HER2 signaling pathway in NSCLC.
View Article and Find Full Text PDFArticle Synopsis
- The Vitamin D Antenatal Asthma Reduction Trial (VDAART) studied children from 6 months to 8 years and found links between specific gene variants and children's body mass index.
- These associations also connected microbiome characteristics tied to obesity with important lipids and amino acids.
- The findings suggest that genetic factors play a role in influencing the microbiome during development and highlight potential biomarkers for childhood obesity and related health issues like insulin resistance and type 2 diabetes.
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!