A5038806492- RNA Research and Splicing
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Cervical Cancer and HPV Research
- Epigenetics and DNA Methylation
- Immune Cell Function and Interaction
- Computational Drug Discovery Methods
- Immunotherapy and Immune Responses
- Virus-based gene therapy research
- PI3K/AKT/mTOR signaling in cancer
- Autophagy in Disease and Therapy
- Alzheimer's disease research and treatments
- T-cell and B-cell Immunology
- Research on Leishmaniasis Studies
- Cholinesterase and Neurodegenerative Diseases
- Mast cells and histamine
- Hippo pathway signaling and YAP/TAZ
- Trypanosoma species research and implications
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- Neurogenesis and neuroplasticity mechanisms
- Genetics and Neurodevelopmental Disorders
- Receptor Mechanisms and Signaling
- Barrier Structure and Function Studies
- Cancer-related gene regulation
Inserm
2005-2024
Université de franche-comté
2014-2024
Université Bourgogne Franche-Comté
2017-2021
Centre National de la Recherche Scientifique
2005-2014
Université de Strasbourg
2009-2014
Institute for Research in Immunology and Cancer
2013
Université de Montréal
2012-2013
Merck Serono (Italy)
2012
Merck Serono (Switzerland)
2011
Institut de génétique et de biologie moléculaire et cellulaire
2007-2008
The eukaryotic translation initiation factor eIF4E is a potent oncogene that promotes the nuclear export and of specific transcripts. Here, we have discovered alters cytoplasmic face pore complex (NPC), which leads to enhanced mRNA target mRNAs. Specifically, substantially reduces major component fibrils NPC, RanBP2, relocalizes an associated nucleoporin, Nup214, elevates RanBP1 RNA factors, Gle1 DDX19. Genetic or pharmacological inhibition impedes these effects. RanBP2 overexpression...
Recognition of the methyl-7-guanosine (m 7 G) cap structure on mRNA is an essential feature metabolism and thus gene expression. Eukaryotic translation initiation factor 4E (eIF4E) promotes translation, export, proliferation, oncogenic transformation dependent this cap-binding activity. eIF4E–cap recognition mediated via complementary charge interactions positively charged m G between negative π-electron clouds from two aromatic residues. Here, we demonstrate that a variant subfamily,...
Differentiation of naïve CD4 T cells toward the helper 1 (T(H)1) and 2 (T(H)2) fates involves transcriptional repression enhancement, respectively, Il4 Il13, adjacent chromosome 11 genes encoding canonical T(H)2 cytokines interleukin-4 interleukin-13. Proper execution this developmental fate choice during immune responses is critical to host defense and, when misregulated, leads susceptibility infectious microbes allergic autoimmune diseases. Here, using chromatin immunoprecipitation real...
Flavaglines constitute a family of natural anticancer compounds. We present here 3 (FL3), the first synthetic flavagline that inhibits cell proliferation and viability (IC50 ≈ 1 nM) at lower doses than did parent compound, racemic rocaglaol. Compound enhanced doxorubicin cytotoxicity in HepG2 cells retained its potency against adriamycin-resistant lines without inducing cardiomyocyte toxicity. induced apoptosis HL60 Hela by triggering translocation Apoptosis Inducing Factor (AIF) caspase-12...
Il4 and Il13 encode the canonical T helper 2 (T H 2) cytokines responsible both for promoting immune responses against extracellular pathogens and, when misregulated, causing allergic autoimmune disease. The expression potential of these genes undergoes developmentally programmed repression enhancement during commitment naïve CD4 + cells to mature 1 1) fates, respectively. Thus, like globin locus, cytokine locus provides a highly tractable system study developmental fate choice leading...
Metastatic lymph node 51 [MLN51 (also known as CASC3)] is a component of the exon junction complex (EJC), which assembled on spliced mRNAs and plays important roles in post-splicing events. The four proteins EJC core, MLN51, MAGOH, Y14 EIF4AIII shuttle between cytoplasm nucleus. However, unlike last three, MLN51 mainly detected cytoplasm, suggesting that it an additional function this compartment. In present study, we show recruited into cytoplasmic aggregates stress granules (SGs) together...
The exon junction complex (EJC) is loaded onto mRNAs as a consequence of splicing and regulates multiple posttranscriptional events. MLN51, Magoh, Y14, eIF4A3 form highly stable EJC core, but where this tetrameric assembled in the cell remains unclear. Here we show that factors are enriched domains term perispeckles visible doughnuts around nuclear speckles. Fluorescence resonance energy transfer analyses assembly mutants do not store free subunits, instead for cores. At ultrastructural...
Multitarget-directed ligands (MTDLs) are considered a promising therapeutic strategy to address the multifactorial nature of Alzheimer's disease (AD). Novel MTDLs have been designed as inhibitors human acetylcholinesterases/butyrylcholinesterases, monoamine oxidase A/B, and glycogen synthase kinase 3β calcium channel antagonists via Biginelli multicomponent reaction. Among these MTDLs, (±)-BIGI-3h was identified new hit compound showing in vitro balanced activities toward aforementioned...
High-risk human papillomaviruses are the etiological agents of cervical cancer and HPV16 is most oncogenic genotype. Immortalization transformation infected cells requires overexpression two viral oncoproteins E6 E7 following HPV DNA integration into host cell genome. Integration often leads to loss E2 open reading frame corresponding protein can no longer act as a transcriptional repressor on p97 promoter. Recently, it has been proposed that long control region methylation also contributes...
Abstract High-risk Human Papillomavirus infections are responsible for anogenital and oropharyngeal cancers. Alternative splicing is an important mechanism controlling HPV16 gene expression. Modulation in the splice pattern leads to polycistronic early transcripts encoding a full length E6 oncoprotein or truncated proteins, commonly named E6*. Spliced E6*I most abundant RNAs produced HPV-related To date, biological function of isoform remains controversial. In this study, we identified, by...
The molecular mechanisms governing γ-secretase cleavage specificity are not fully understood. Herein, we demonstrate that extending the transmembrane domain of amyloid precursor protein-derived C99 substrate in proximity to cytosolic face strongly influences specificity. Sequential insertion leucines or replacement membrane-anchoring lysines by elevated production Aβ42, whilst lowering Aβ40. A single was sufficient produce this phenotype, suggesting helical length distal ε-site is a critical...
Background Despite numerous in vivo evidences that Tumor Necrosis Factor Receptor-Associated 4 (TRAF4) plays a key biological function, how it works at the cellular and molecular level remains elusive. Methodology/Principal Findings In present study, we show using immunofluorescence immuohistochemistry TRAF4 is novel player tight junctions (TJs). connected to assembled TJs confluent epithelial cells, but accumulates cytoplasm and/or nucleus when are open isolated cells or EGTA-treated cells....
Metastatic Lymph Node 51 (MLN51) is a core component of the exon junction complex (EJC), which loaded on spliced mRNAs and plays an essential role in their fate. Unlike three other EJC components (eIF4AIII, Magoh Y14), MLN51 mainly located cytoplasm where it key stress granules assembly. In this study, we further investigated cytoplasmic MLN51. We show that new processing bodies (P-bodies). When overexpressed, localizes novel small foci. These contain RNA, directed movements, are distinct...
The propensity of naive CD4 T cells to become helper (Th) type 2 correlates with susceptibility infection by the protozoal parasite Leishmania major. Using genetic linkage analysis, we earlier identified Dice1 as a Th2 cell bias-controlling quantitative trait locus on chromosome 16. interval-specific congenic mapping, now resolve into two independent loci, Dice1.1 and Dice1.2, which control Il4 expression from Th thereby indirectly bias. Interestingly, only one intervals containing...
HPV16 is the most carcinogenic human papillomavirus and causes >50% of cervical cancers, majority anal cancers 30% oropharyngeal squamous cell carcinomas. HPV carcinogenesis relies on continuous expression two main viral oncoproteins E6 E7 that target >150 cellular proteins. Among them, epigenetic modifiers, including DNA Methyl Transferases (DNMT), are dysregulated, promoting an aberrant methylation pattern in HPV‑positive cancer cells. It has been previously reported treatment cells with...
High-risk human papillomavirus (HPV) infection is a causal factor in oropharyngeal and gynecological malignancies, development of HPV-targeted immunotherapy could be used to treat patients with these cancers. T cell-mediated adoptive targeting E6 E7, two HPV16 proteins consistently expressed tumor cells, appears both attractive safe. However, isolation HPV-specific cells difficult owing the low frequency cell precursors peripheral blood. In addition, HPV-positive cancer often down-regulate...
High-risk human papillomavirus (hrHPVs), particularly HPV16 and HPV18, are the etiologic factors of ano-genital cancers some head neck squamous cell carcinomas (HNSCCs). Viral E6 E7 oncoproteins, controlled at both transcriptional post-transcriptional levels, drive hrHPVs-induced carcinogenesis. In present study, we investigated implication DEAD-box helicase eukaryotic translation initiation factor 4A3 (eIF4A3,) an Exon Junction Complex factor, in regulation gene expression. Our data...
Abstract Noncoding RNA transcripts mapping to intergenic regions of the Il4-Il13 locus have been detected in Th2 cells harboring transcriptionally permissive Il4 and Il13 genes but not Th1 where these are repressed. This correlation has given rise idea that transcription may be involved maintaining “open” chromatin structure cells. We present evidence from real-time RT-PCR, nuclear run on, immunoprecipitation 5,6-dichlorobenzimidazole 1-β-d-ribofuranoside-mediated transcriptional inhibition...
The pathway of selective autophagy, leading to a targeted elimination specific intracellular components, is mediated by the ATG8 proteins, and has been previously suggested be involved in regulation Epithelial–mesenchymal transition (EMT) during cancer’s etiology. However, molecular factors steps autophagy occurring EMT remain unclear. We therefore analyzed cohort lung adenocarcinoma tumors using transcriptome analysis immunohistochemistry, found that expression genes correlated with...
EMT is a reversible cellular process that linked to gene expression reprogramming, which allows for epithelial cells undergo phenotypic switch acquire mesenchymal properties. associated with cancer progression and therapeutic resistance it known that, during the EMT, many stress response pathways, such as autophagy NMD, are dysregulated. Therefore, our goal was study regulation of ATG8 family members (GABARAP, GABARAPL1, LC3B) by NMD identify molecular links between these two processes...
One of the major hallmarks Alzheimer's disease is deposition amyloid-beta (Abeta) peptides in brain which are generated following proteolytic processing amyloid precursor protein (APP) by beta-site APP cleaving enzyme (BACE1) and gamma-secretase. Gamma-secretase a large complex comprising four subunits: presenilin, nicastrin, Pen-2 Aph-1 mediates intramembrane proteolysis number proteins including Notch. Recently, novel gamma-secretase activating (GSAP) was identified that interacts with...