A5041788670- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Advanced biosensing and bioanalysis techniques
- Tryptophan and brain disorders
- Cancer Immunotherapy and Biomarkers
- Protein Degradation and Inhibitors
- Cancer-related Molecular Pathways
- RNA Interference and Gene Delivery
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Advanced Breast Cancer Therapies
- Protein Tyrosine Phosphatases
- Immune Cell Function and Interaction
- Cancer Treatment and Pharmacology
- Epigenetics and DNA Methylation
- Renal and related cancers
- Immune cells in cancer
- Peptidase Inhibition and Analysis
- Lipid metabolism and biosynthesis
- Metabolomics and Mass Spectrometry Studies
- Cholesterol and Lipid Metabolism
- Ubiquitin and proteasome pathways
- HIV Research and Treatment
- Advanced Biosensing Techniques and Applications
The Netherlands Cancer Institute
2020-2025
Oncode Institute
2020-2025
German Center for Infection Research
2025
Centre National de la Recherche Scientifique
2014-2019
Institut de Génomique Fonctionnelle
2015-2019
Université de Montpellier
2019
Inserm
2019
Activated T cells secrete interferon-γ, which triggers intracellular tryptophan shortage by upregulating the indoleamine 2,3-dioxygenase 1 (IDO1) enzyme1-4. Here we show that despite depletion, in-frame protein synthesis continues across codons. We identified tryptophan-to-phenylalanine codon reassignment (W>F) as major event facilitating this process, and pinpointed tryptophanyl-tRNA synthetase (WARS1) its source. call these W>F peptides 'substitutants' to distinguish them from genetically...
Plasma membranes of cultured cells contain high affinity receptors for density lipoprotein (HDL) that appear to mediate removal excess intracellular cholesterol. Recent studies using ligand blot analysis have identified a 110-kDa membrane protein which has features predicted an HDL receptor, in it preferentially binds apolipoproteins and undergoes up-regulation response cholesterol loading cells. In this study, we isolated cDNA clone from expression library antibody raised against partially...
Perturbation of protein phosphorylation represents an attractive approach to cancer treatment. Besides kinase inhibitors, phosphatase inhibitors have been shown anti-cancer activity. A prime example is the small molecule LB-100, inhibitor phosphatases 2A/5 (PP2A/PP5), enzymes that affect cellular physiology. LB-100 has proven effective in pre-clinical models combination with immunotherapy, but molecular underpinnings this synergy remain understood poorly. We report here a sensitivity mRNA...
mRNA translation is a highly conserved and tightly controlled mechanism for protein synthesis. Despite quality control mechanisms, amino acid shortage in melanoma induces aberrant proteins by ribosomal frameshifting. The extent the underlying mechanisms related to this phenomenon are yet unknown. Here, we show that tryptophan depletion-induced frameshifting widespread cancer. We termed event sloppiness strikingly observed its association with MAPK pathway hyperactivation. Sloppiness...
Through intercellular signalling, the somatic compartment of foetal testis is able to program primordial germ cells undergo spermatogenesis. Fibroblast growth factor 9 and several members transforming β superfamily are involved in this process testis, counteracting induction meiosis by retinoic acid activating germinal mitotic arrest. Here, using vitro vivo approaches, we show that prostaglandin D2 (PGD2), which produced through both L-Pgds H-Pgds enzymatic activities cell compartments plays...
The use of alternative promoters, splicing, and cleavage polyadenylation (APA) generates mRNA isoforms that expand the diversity complexity transcriptome. Here, we uncovered thousands previously undescribed 5′ uncapped polyadenylated transcripts (5′ UPTs). We show these resist exonucleases due to a highly structured RNA N6-methyladenosine modification at their termini. UPTs appear downstream APA sites within host genes are induced upon activation. Strong enrichment in polysomal fractions...
Highlights•IFNγ-induced tryptophan depletion induces W>F substitutants neoepitopes•W>F neoepitopes are widespread and shared between cancer types•W>F targets of adoptive T cell therapy•Conventional therapy can benefit from targeting neoepitopesSummaryProlonged exposure to interferon-gamma (IFNγ) the associated increased expression enzyme indoleamine 2,3-dioxygenase 1 (IDO1) create an intracellular shortage in cells, which stimulates ribosomal frameshifting phenylalanine (W>F) codon...
Abstract Mitosis is a critical phase of the cell cycle and vulnerable point where cancer cells can be effectively disrupted, leading to death inhibition tumor growth. However, challenges such as drug resistance remain significant in clinical applications. During mitosis, mRNA translation generally downregulated, while non-canonical specific transcripts proceeds. Here, we demonstrate that mitotic redistribute ribosomes toward 5’ untranslated region (5’ UTR) start coding sequence (CDS),...
Abstract Messenger RNA (mRNA) translation is a tightly controlled process frequently deregulated in cancer. Key to this deregulation are transfer RNAs (tRNAs), whose expression, processing and post-transcriptional modifications often altered cancer support cellular transformation. In conditions of limiting levels amino acids, control protein synthesis leads aberrant production the form ribosomal frameshifting or misincorporation non-cognate acids. Here, we studied leucine, an essential acid...
Abstract We present here a novel method for the semi-quantitative detection of low abundance proteins in solution that is both fast and simple. It based on Homogenous Time Resolved Förster Resonance Energy Transfer (HTRF), between lanthanide labeled donor antibody d2 or XL665 acceptor are raised against different epitopes same target. This approach we termed “Tandem-HTRF”, can specifically reveal rare polypeptides from only few microliters cellular lysate within one hour 384-well plate...