A5032931448- HIV Research and Treatment
- Melanoma and MAPK Pathways
- Cancer-related Molecular Pathways
- HIV/AIDS drug development and treatment
- Cancer, Hypoxia, and Metabolism
- RNA Interference and Gene Delivery
- Cell Adhesion Molecules Research
- RNA and protein synthesis mechanisms
- PI3K/AKT/mTOR signaling in cancer
- Protein Structure and Dynamics
- Protein Kinase Regulation and GTPase Signaling
- RNA Research and Splicing
- Cellular Mechanics and Interactions
- Cutaneous Melanoma Detection and Management
- HIV/AIDS Research and Interventions
- Retinal Development and Disorders
- Glioma Diagnosis and Treatment
- Hippo pathway signaling and YAP/TAZ
- Immune Cell Function and Interaction
- Cell death mechanisms and regulation
- Hepatitis B Virus Studies
- Skin Protection and Aging
- Kruppel-like factors research
- Fibroblast Growth Factor Research
- TGF-β signaling in diseases
Inserm
2010-2024
Institut Curie
2010-2024
Université Paris Sciences et Lettres
2018-2024
Université Paris-Saclay
2019-2024
Centre National de la Recherche Scientifique
2006-2022
La Ligue Contre le Cancer
2017-2022
Centre Hospitalier d'Orsay
2019
Université Paris-Sud
2012-2018
Université Paris Cité
2000-2011
Sorbonne Paris Cité
2011
Viral protein R (Vpr) encoded by HIV-1 is a facultative inducer of apoptosis. When added to intact cells or purified mitochondria, micromolar and submicromolar doses synthetic Vpr cause rapid dissipation the mitochondrial transmembrane potential (ΔΨm), as well release apoptogenic proteins such cytochrome c apoptosis inducing factor. The same structural motifs relevant for cell killing are responsible mitochondriotoxic effects Vpr. Both cytotoxic prevented Bcl-2, an inhibitor permeability...
Viral protein R (Vpr), an apoptogenic accessory encoded by HIV-1, induces mitochondrial membrane permeabilization (MMP) via a specific interaction with the permeability transition pore complex, which comprises voltage-dependent anion channel (VDAC) in outer (OM) and adenine nucleotide translocator (ANT) inner membrane. Here, we demonstrate that synthetic Vpr-derived peptide (Vpr52-96) specifically binds to intermembrane face of ANT affinity nanomolar range. Taking advantage this interaction,...
Abstract Purpose: The emergence of skin tumors in patients treated with sorafenib or more recent BRAF inhibitors is an intriguing and potentially serious event. We carried out a clinical, pathologic, molecular study lesions occurring receiving sorafenib. Experimental Design: Thirty-one from were characterized clinically pathologically. DNA extracted the was screened for mutation hot spots HRAS, NRAS, KiRAS, TP53, EGFR, BRAF, AKT1, PI3KCA, TGFBR1, PTEN. Biological effect studied vivo normal...
Accumulating evidence points to inflammation as a promoter of carcinogenesis. MyD88 is an adaptor molecule in TLR and IL-1R signaling that was recently implicated tumorigenesis through proinflammatory mechanisms. Here we have shown also required cell-autonomous fashion for RAS-mediated carcinogenesis mice vivo MAPK activation transformation vitro. Mechanistically, bound the key MAPK, Erk, prevented its inactivation by phosphatase, MKP3, thereby amplifying canonical RAS pathway. The relevance...
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy. Current treatments, based on intensive chemotherapy regimens provide overall survival rates of ∼85% in children and <50% adults, calling the search new therapeutic options. We previously reported that targeting receptor (TCR) T-ALL with anti-CD3 (αCD3) monoclonal antibodies (mAbs) enforces a molecular program akin to thymic negative selection, major developmental checkpoint normal development; induces...
Gag protein oligomerization, an essential step during virus assembly, results in budding of spherical particles. This process is critically dependent on the spacer p2, located between capsid and nucleocapsid proteins. P2 contributes also, association with NCp7, to specific recognition HIV-1 packaging signal resulting viral genome encapsidation. There no structural information about 20 last amino acids C-terminal part (CA[CTD]) molecular mechanism assembly. In this study structure a peptide...
Abstract NRAS and its effector BRAF are frequently mutated in melanoma. Paradoxically, CRAF but not was shown to be critical for various RAS-driven cancers, raising the question of role RAF proteins NRAS-induced Here, using conditional ablation Raf genes mouse melanoma models, we investigate their contribution tumour progression, from onset benign tumours malignant maintenance. We show that expression is required ERK activation nevi development, demonstrating a early stages NRAS-driven After...
The human immunodeficiency virus (HIV-1) nucleocapsid protein NCp7 containing two CX 2CX 4HX 4C-type zinc fingers was proposed to be involved in reverse transcriptase (RT)-catalyzed proviral DNA synthesis through promotion of tRNA3Lys annealing the RNA primer binding site, improvement strand transfers, and enhancement RT processivity. structural characteristics are crucial because mutations altering finger domain conformation led noninfectious viruses characterized by defects provirus...
ABSTRACT Viral protein R (Vpr) of human immunodeficiency virus type 1 is produced late in the life cycle and assembled into virion through binding to Gag protein. It known play a significant role early viral by facilitating nuclear import preintegration complex nondividing cells. Vpr also able interact with nucleic acids, we show here that it induces condensation plasmid DNA. We have explored possibility using these properties DNA transfection experiments. report C-terminal half (Vpr 52–96 )...
Among the 518 protein kinases encoded by human kinome, several of them act as oncoproteins in cancers. Like other eukaryotic genes, oncogenes encoding are frequently subjected to alternative splicing coding well noncoding sequences. In present paper, we will illustrate how can significantly impact on physiological functions oncogenic kinases, demonstrated mouse genetic model studies. This includes examples membrane-bound tyrosine receptors (FGFR2, Ret, TrkB, ErbB4, and VEGFR) cytosolic...
The B-Raf proto-oncogene encodes several isoforms resulting from alternative splicing in the hinge region upstream of kinase domain. presence exon 8b B2-Raf(8b) isoform and 9b B3-Raf(9b) differentially regulates by decreasing increasing MEK activating oncogenic activities, respectively. Using different cell systems, we investigated here molecular basis this regulation. We show that exons interfere with ability N-terminal to interact inhibit C-terminal domain, thus modulating autoinhibition...
The HIV‐1 protein Vpr circulates in the serum of seropositive individuals and cerebrospinal fluid AIDS patients with neurological disorders. triggers apoptosis numerous cell types after extracellular addition, vpr gene transfer or context viral infection. Moreover, vivo , transgenic mice over‐expressing have enhanced T lymphocytes apoptosis. In previous studies, we suggested that apoptotic activities were because its binding to adenine nucleotide translocator (ANT), a mitochondrial ATP/ADP...
B-Raf and C-Raf kinases have emerged as critical players in melanoma. However, little is known about their role during development homeostasis of the melanocyte lineage. Here, we report that knockout B-raf C-raf genes this lineage results normal pigmentation at birth with no defect migration, proliferation, or differentiation melanoblasts mouse hair follicles. In contrast, double raf mice displayed graying resulting from a cell-cycle entry stem cells (MSCs) subsequent depletion follicle...
Intensive chemotherapeutic regimens with craniospinal irradiation have greatly improved survival in medulloblastoma patients. However, markedly differs among molecular subgroups and their biomarkers are unknown. Through unbiased screening, we found Schlafen family member 11 (SLFN11), which is known to improve response DNA damaging agents various cancers, be one of the top prognostic markers medulloblastomas. Hence, explored expression functions SLFN11 medulloblastoma.SLFN11 for each subgroup...
Combined inhibition of HIV-1 reverse transcriptase and protease has significantly improved the treatment AIDS. Nevertheless, resistance to these drugs occurs rapidly because viral mutations, emphasizing importance identifying novel retroviral targets develop new drug combinations. The critical role played by nucleocapsid protein NCp7 at different steps retrovirus life cycle makes it an attractive target for development antiviral agents. contains two highly conserved zinc fingers is...
Abstract The MITF transcription factor and the RAS/RAF/MEK/ERK pathway are two interconnected main players in melanoma. Understanding how activity is regulated represents a key question since its dynamic modulation involved phenotypic plasticity of melanoma cells their resistance to therapy. By investigating role ARAF NRAS-driven mouse through mass spectrometry experiments followed by functional siRNA-based screen, we unexpectedly identified as direct partner. Interestingly, this interaction...
The modification of zinc-binding residues inside the conserved CCHC motif human immunodeficiency virus type 1 NCp7, in particular into CCHH, induces a complete loss infectivity. Since mutant His28NCp7 has been shown to be devoid infectivity vivo, structure-function relationships His28(12-53)NCp7 were investigated by nuclear magnetic resonance and surface plasmonic resonance. Although Cys28-->His mutation modifies drastically structure core domain (residues 12 53) still interacts with...
Article22 July 2019Open Access Source DataTransparent process An autocrine ActivinB mechanism drives TGFβ/Activin signaling in Group 3 medulloblastoma Morgane Morabito Institut Curie, Orsay, France INSERM U1021, Centre Universitaire, CNRS UMR 3347, University Paris Sud – Paris-Saclay, PSL Research University, Paris, Search for more papers by this author Magalie Larcher Florence MG Cavalli The Arthur and Sonia Labatt Brain Tumour Center, Hospital Sick Children, Toronto, ON, Canada...