Simian Virus 40 (SV40) large T antigen (T Ag) is a multifunctional viral oncoprotein that regulates viral and cellular transcriptional activity. However, the mechanisms by which such regulation occurs remain unclear. Here we show that T antigen represses CBP-mediated transcriptional activity. This repression is concomitant with histone H3 deacetylation and is TSA sensitive. Moreover, our results demonstrate that T antigen interacts with HDAC1 in vitro in an Rb-independent manner. In addition, the overexpression of HDAC1 cooperates with T antigen to antagonize CBP transactivation function and correlates with chromatin deacetylation of the TK promoter. Finally, decreasing HDAC1 levels with small interfering RNA (siRNA) partially abolishes T antigen-induced repression. These findings highlight the importance of the histone acetylation/deacetylation balance in the cellular transformation mediated by oncoviral proteins.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1874590 | PMC |
| http://dx.doi.org/10.1093/nar/gkl1113 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
CTSG is a prognostic marker involved in immune infiltration and inhibits tumor progression though the MAPK signaling pathway in non-small cell lung cancer.
J Cancer Res Clin Oncol
December 2024
Department of Respiratory Medicine, The Fuyang Affiliated Hospital of Anhui Medical University, Fuyang, 236000, Anhui, China.
Purpose: This study aims to investigate the biological roles and molecular mechanisms of Cathepsin G (CTSG) in the progression of non-small cell lung cancer (NSCLC).
Methods: Western blotting and immunohistochemistry analyses of clinical samples were performed to determine the expression levels of CTSG in patients with NSCLC. Bioinformatic analysis of clinical datasets was conducted to evaluate the correlation between CTSG and lymph node metastasis, tumor stage, and immune cell infiltration.
Histone Modification-Dependent Transcriptional Regulation of Defence Genes in Early Response of Arabidopsis to Spodoptera litura Attack.
Plant Cell Environ
December 2024
Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of Science, Tokyo, Japan.
Histone modification is a cellular process for transcriptional regulation. In herbivore-damaged plants, activation of genes involved in defence responses is required for antiherbivore properties, but little is known about how the chromatin remodelling system is involved. In Arabidopsis (Arabidopsis thaliana) plants responding to Spodoptera litura larvae, HAC1 and HDA6, a histone acetyltransferase and a histone deacetylase, respectively, were found here to be involved in histone H3 (Lys9; H3K9) acetylation/deacetylation at the promoter region of the plant defensin gene PDF1.
View Article and Find Full Text PDFPost-translational modifications (PTMs) are critical regulators of protein function and cellular signaling. While histone deacetylation by histone deacetylases (HDACs) is well established, the role of specific HDACs in modulating non-histone protein PTMs, particularly in an infectious context, is poorly understood. Here, we reveal a pivotal role for HDAC6 in orchestrating periodontal inflammation through its dual regulatory effects on FoxO1 acetylation and phosphorylation.
View Article and Find Full Text PDFHDAC10 switches NLRP3 modification from acetylation to ubiquitination and attenuates acute inflammatory diseases.
Cell Commun Signal
December 2024
Department of Immunology, School of Basic Medical Sciences, Cheeloo college of Medicine, Shandong University, Jinan, 250012, China.
Background: The NOD-like receptor protein (NLRP)3 inflammasome is at the signaling hub center to instigate inflammation in response to pathogen infection or oxidative stress, and its tight control is pivotal for immune defense against infection while avoiding parallel intensive inflammatory tissue injury. Acetylation of NLRP3 is critical for the full activation of NLRP3 inflammasome, while the precise regulation of the acetylation and deacetylation circuit of NLRP3 protein remained to be fully understood.
Methods: The interaction between histone deacetylase 10 (HDAC10) and NLRP3 was detected by immunoprecipitation and western blot in the HDAC10 and NLRP3 overexpressing cells.
The SIRT6 allosteric activator MDL-800 suppresses calcium oxalate nephrocalcinosis by alleviating inflammatory and renal damage.
Int Immunopharmacol
December 2024
Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China; Institute of Urology, Anhui Medical University, Hefei, China; Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, China. Electronic address:
Article Synopsis
- Kidney stones are primarily made of calcium oxalate and can cause inflammation and damage in kidney cells, leading to a condition known as CaOx nephrocalcinosis.
- The study tested a new drug, MDL-800, which acts as an allosteric agonist for Sirtuin 6 (SIRT6), showing it can reduce kidney cell damage and inflammation caused by calcium oxalate crystals in both cell cultures and animal models.
- MDL-800 works by decreasing levels of inflammatory proteins and enhancing SIRT6's function, offering a potential new treatment approach for kidney damage linked to calcium oxalate stones.
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!