A5077313197- Ubiquitin and proteasome pathways
- Histone Deacetylase Inhibitors Research
- Cancer-related Molecular Pathways
- Peptidase Inhibition and Analysis
- CRISPR and Genetic Engineering
- Immunotherapy and Immune Responses
- Acute Myeloid Leukemia Research
- Hedgehog Signaling Pathway Studies
- Blood disorders and treatments
- Microtubule and mitosis dynamics
- Aging, Elder Care, and Social Issues
- NF-κB Signaling Pathways
- MicroRNA in disease regulation
- Immune cells in cancer
- Immune Cell Function and Interaction
- Virus-based gene therapy research
- Genetic and Kidney Cyst Diseases
- HIV/AIDS drug development and treatment
- Toxoplasma gondii Research Studies
- Glycosylation and Glycoproteins Research
- HIV Research and Treatment
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Protein Degradation and Inhibitors
- Retinoids in leukemia and cellular processes
- Cancer, Hypoxia, and Metabolism
Centre National de la Recherche Scientifique
2005-2024
Institut de Génétique Moléculaire de Montpellier
2008-2024
Université de Montpellier
2010-2024
La Ligue Contre le Cancer
2021-2022
Howard Hughes Medical Institute
2006
University of Arizona
2006
Inserm
2005-2006
Institut Cochin
2005-2006
Institute of Molecular Biology and Biophysics
2006
Sorbonne Université
2005
Gli3 is a zinc finger transcription factor proteolytically processed into truncated repressor lacking C-terminal activation domains. processing stimulated by protein kinase A (PKA) and inhibited Hedgehog signaling, major signaling pathway in vertebrate development disease. We show here that multisite glycogen synthase 3beta (GSK3beta) phosphorylation ubiquitination SCFbetaTrCP are required for processing. identified multiple betaTrCP-binding sites related to the DSGX2-4S motif Gli3, which...
The insertion of a DNA copy its RNA genome into chromosome the hostcell is mediated by viral integrase with help mostlyuncharacterized cellular cofactors. We have recently described that thetranscriptional co-activator LEDGF/p75 strongly interacts HIV-1integrase. Here we show interaction HIV-1 isimportant for replication. Using multiple approaches includingtwo-hybrid studies, random and directed mutagenesis, coulddemonstrate virus harboring single mutation disruptsintegrase-LEDGF/p75...
Resistance to chemotherapeutic drugs is a major cause of treatment failure in acute myeloid leukemias (AML). To better characterize the mechanisms chemoresistance, we first identified genes whose expression dysregulated AML cells resistant daunorubicin or cytarabine, main used for induction therapy. The found be activated are mostly linked immune signaling and inflammation. Among them, strong upregulation NOX2 NAPDH oxidase subunit (CYBB, CYBA, NCF1, NCF2, NCF4 RAC2). ensuing increase NADPH...
Acute Myeloid Leukemias (AML) are severe hematomalignancies with dismal prognosis. The post-translational modification SUMOylation plays key roles in leukemogenesis and AML response to therapies. Here, we show that TAK-981 (subasumstat), a first-in-class inhibitor, is endowed potent anti-leukemic activity various preclinical models of AML. targets cell lines patient blast cells vitro vivo xenografted mice minimal toxicity on normal hematopoietic cells. Moreover, it synergizes 5-azacitidine...
Dendritic cells (DCs) play a key role in the induction of adaptive and memory immune responses. Upon encounter with pathogens, they undergo complex maturation process migrate toward lymphoid organs where stimulate effector cells. This is associated dramatic transcriptome changes, pointing to paramount for transcription factors DC activation function. The regulation these are however ill-defined require characterization. Among those, AP-1 family dimeric complexes an acknowledged control...
Targeted mutagenesis directed by oligonucleotides (ONs) is a promising method for manipulating the genome in higher eukaryotes. In this study, we have compared gene editing different ONs on two new target sequences, eBFP and rd1 mutant photoreceptor βPDE cDNAs, which were integrated as single copy transgenes at same genomic site 293T cells. Interestingly, antisense superior to sense one only, showing that sequence can itself impart strand-bias editing. The most efficient short 25 nt with...
Genotoxicants have been used for decades as front-line therapies against cancer on the basis of their DNA-damaging actions. However, some non-DNA-damaging effects are also instrumental killing dividing cells. We report here that anthracycline Daunorubicin (DNR), one main drugs to treat Acute Myeloid Leukemia (AML), induces rapid (3 h) and broad transcriptional changes in AML The regulated genes particularly enriched controlling cell proliferation death, well inflammation immunity. These...
Abstract Natural Killer (NK) cells play a pivotal role in mounting an anti-cancer immune response. Patients with diminished NK number and activity face less favorable prognosis. Promising therapeutic strategies include the adoptive transfer of or reactivation patients’ own cells. TAK-981, first-in-class inhibitor SUMOylation undergoing phase I/II clinical trials for cancer, is emerging as immunomodulatory drug. Here, we demonstrate that TAK-981 activates from healthy donors patients Acute...
Ubiquitin serves as a molecular zipcode to direct and sort ubiquitinylated proteins into distinct biological pathways. Although novel modes of ubiquitin interaction have recently been characterized, conventional ubiquitin-binding domains (UBDs) recognize through hydrophobic pocket centered around isoleucine 44 lined by residues in beta sheets 3 4. In this study, we report mode between the cyclin-dependent kinase subunit Saccharomyces cerevisiae, Cks1p, an adaptor protein involved...
Cks proteins are physical interactors of cyclin-dependent kinases that play a central role in eukaryotic cell cycle progression, both activation and degradation signalling pathways. Functionally, these small stabilize cdk-cyclin complexes behave as adaptors through recruitment variety proteins, including phosphoprotein regulators Wee1, Myt1 Cdc25, the Skp2 ubiquitin ligase component, proteasomal subunits. In budding yeast, Cks1p is implicated transcriptional regulation association with loci,...
Abstract Genotoxicants have been used for decades as front-line therapies against cancer on the basis of their DNA-damaging actions. However, some non-DNA-damaging effects are also instrumental killing dividing cells. We report here that anthracycline Daunorubicin (DNR), one main drugs to treat Acute Myeloid Leukemia (AML), induces broad transcriptional changes in AML cells before cell death induction. The regulated genes particularly enriched controlling proliferation and death, well...