Search results for "post-translational modification"

Comprehensive analysis of interacting proteins and genome-wide location studies of the Sas3-dependent NuA3 histone acetyltransferase complex

2014

Highlights • We characterise Sas3p and Gcn5p active HAT complexes in WT and deleted TAP-strains. • We confirm that Pdp3p interacts with NuA3, histones and chromatin regulators. • Pdp3p MS-analysis reveals its phosphorylation, ubiquitination and methylation. • Sas3p can substitute Gcn5p in acetylation of histone H3K14 but not of H3K9. • Genome-wide profiling of Sas3p supports its involvement in transcriptional elongation.

Editorial: The Role of Protein Post-Translational Modifications in Protein-RNA Interactions and RNP Assemblies

2022

New approach to generating insights for aging research based on literature mining and knowledge integration.

2017

The proportion of the elderly population in most countries worldwide is increasing dramatically. Therefore, social interest in the fields of health, longevity, and anti-aging has been increasing as well. However, the basic research results obtained from a reductionist approach in biology and a bioinformatic approach in genome science have limited usefulness for generating insights on future health, longevity, and anti-aging-related research on a case by case basis. We propose a new approach that uses our literature mining technique and bioinformatics, which lead to a better perspective on research trends by providing an expanded knowledge base to work from. We demonstrate that our approach …

Non-small cell lung cancer (NSCLC), EGFR downstream pathway activation and TKI targeted therapies sensitivity: Effect of the plasma membrane-associat…

2017

Adenocarcinoma of Non-Small Cell Lung Cancer (NSCLC) is a severe disease. Patients carrying EGFR mutations may benefit from EGFR targeted therapies (e.g.: gefitinib). Recently, it has been shown that sialidase NEU3 directly interacts and regulates EGFR. In this work, we investigate the effect of sialidase NEU3 overexpression on EGFR pathways activation and EGFR targeted therapies sensitivity, in a series of lung cancer cell lines. NEU3 overexpression, forced after transfection, does not affect NSCLC cell viability. We demonstrate that NEU3 overexpression stimulates the ERK pathway but this activation is completely abolished by gefitinib treatment. The Akt pathway is also hyper-activated upo…

Pharmacological targeting of the novel β-catenin chromatin-associated kinase p38α in colorectal cancer stem cell tumorspheres and organoids

2021

AbstractThe prognosis of locally advanced colorectal cancer (CRC) is currently unsatisfactory. This is mainly due to drug resistance, recurrence, and subsequent metastatic dissemination, which are sustained by the cancer stem cell (CSC) population. The main driver of the CSC gene expression program is Wnt signaling, and previous reports indicate that Wnt3a can activate p38 MAPK. Besides, p38 was shown to feed into the canonical Wnt/β-catenin pathway. Here we show that patient-derived locally advanced CRC stem cells (CRC-SCs) are characterized by increased expression of p38α and are “addicted” to its kinase activity. Of note, we found that stage III CRC patients with high p38α levels display…

Protein S-nitrosylation: specificity and identification strategies in plants

2015

SPE Pôle IPM UB; International audience; The role of nitric oxide (NO) as a major regulator of plant physiological functions has become increasingly evident. To further improve our understanding of its role, within the last few years plant biologists have begun to embrace the exciting opportunity of investigating protein S-nitrosylation, a major reversible NO-dependent post-translational modification (PTM) targeting specific Cys residues and widely studied in animals. Thanks to the development of dedicated proteomic approaches, in particular the use of the biotin switch technique (BST) combined with mass spectrometry, hundreds of plant protein candidates for S-nitrosylation have been identi…

Cryptogein signaling in tobacco: in search for nitric oxide targets

2013

Nitric oxide (NO) triggers various physiological responses in plants. Notably, NO is recognized to account for the response to biotic stresses. We previously reported that NO is produced in tobacco cells exposed to cryptogein, a 10 kDa elicitor secreted by the oomycete Phytophthora cryptogea. To decipher the role of NO, we identified and characterized S-nitrosylated proteins in tobacco cell suspensions elicited by cryptogein. Several candidates were identified including the chaperone-like AAA+ATPase CDC48 and a calmodulin isoform (CaM). Interestingly, the Cys residue undergoing S-nitrosylation in CaM is located in the first Ca2+ binding EF hand and is not or poorly conserved in other organi…

p38α regulates actin cytoskeleton and cytokinesis in hepatocytes during development and aging.

2017

[Background]: Hepatocyte poliploidization is an age-dependent process, being cytokinesis failure the main mechanism of polyploid hepatocyte formation. Our aim was to study the role of p38α MAPK in the regulation of actin cytoskeleton and cytokinesis in hepatocytes during development and aging. [Methods]: Wild type and p38α liver-specific knock out mice at different ages (after weaning, adults and old) were used. [Results]: We show that p38α MAPK deficiency induces actin disassembly upon aging and also cytokinesis failure leading to enhanced binucleation. Although the steady state levels of cyclin D1 in wild type and p38α knock out old livers remained unaffected, cyclin B1- a marker for G2/M…

Mechanistic insights into the phosphoryl transfer reaction in cyclin-dependent kinase 2: a QM/MM study

2019

AbstractCyclin-dependent kinase 2 (CDK2) is an important member of the CDK family exerting its most important function in the regulation of the cell cycle. It catalyzes the transfer of the gamma phosphate group from an ATP (adenosine triphosphate) molecule to a Serine/Threonine residue of a peptide substrate. Due to the importance of this enzyme, and protein kinases in general, a detailed understanding of the reaction mechanism is desired. Thus, in this work the phosphoryl transfer reaction catalyzed by CDK2 was revisited and studied by means of hybrid quantum mechanics/molecular mechanics (QM/MM) calculations. Our results show that the base-assisted mechanism is preferred over the substrat…

In vitro anti-inflammatory effects of AZD8999, a novel bifunctional muscarinic acetylcholine receptor antagonist /β2-adrenoceptor agonist (MABA) comp…

2019

Recent evidence indicates that AZD8999 (LAS190792), a novel muscarinic acetylcholine receptor antagonist and β2-adrenoceptor agonist (MABA) in development for chronic respiratory diseases, induces potent and sustained relaxant effects in human bronchi by adressing both muscarinic acetylcholine receptors and β2-adrenoceptor. However, the anti-inflammatory effects of the AZD8999 monotherapy or in combination with corticosteroids are unknown. This study investigates the anti-inflammatory effects of AZD8999 in monotherapy and combined with fluticasone propionate in neutrophils from healthy and chronic obstructive pulmonary disease (COPD) patients. Peripheral blood neutrophils from healthy and C…