A5041795619- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Protein Kinase Regulation and GTPase Signaling
- Microtubule and mitosis dynamics
- Cancer-related Molecular Pathways
- Monoclonal and Polyclonal Antibodies Research
- Ubiquitin and proteasome pathways
- Protist diversity and phylogeny
- Slime Mold and Myxomycetes Research
- Cell Adhesion Molecules Research
- DNA Repair Mechanisms
- Cell death mechanisms and regulation
- Immune Cell Function and Interaction
- RNA and protein synthesis mechanisms
- Cancer, Hypoxia, and Metabolism
- Lung Cancer Treatments and Mutations
- Bone health and treatments
- Estrogen and related hormone effects
- Cancer Genomics and Diagnostics
- Cellular Mechanics and Interactions
- Glycosylation and Glycoproteins Research
- Viral Infectious Diseases and Gene Expression in Insects
- Diatoms and Algae Research
- T-cell and B-cell Immunology
Inserm
2008-2024
Université Toulouse III - Paul Sabatier
2005-2024
Université de Toulouse
2017-2024
Centre de Recherche en Cancérologie de Toulouse
2011-2024
Centre National de la Recherche Scientifique
1993-2024
Institut Claudius Regaud
2004-2018
Toxicologie, Pharmacologie et Signalisation Cellulaire
2008
Institut National de Recherche en Santé Publique
2006
DuPont (United States)
2001
Hôpital Purpan
2000
gamma-Tubulin, a recently discovered member of the tubulin superfamily, is peri-centriolar component considered to be essential for microtubule nucleation. Mouse oocytes and early embryos lack centrioles until blastocyst stage. Thus, mouse allowed us study location gamma-tubulin in animal cells absence centrioles. For this, we used an antiserum directed against specific peptide sequence, which conserved among species. This serum has been characterised both PtK2 cells. We found that it...
ABSTRACT Animal cells undergoing cytokinesis form an inter-cel-lular bridge containing two bundles of microtubules interdigitated at their plus ends, which constitute the midbody. Polyclonal antibodies raised against three specific amino acid sequences γ-tubulin (EEFATEGGDRKDV, NIIQGEADPTDVHKSL and EYHAATRPDYISWGTQEQ) specifically stained centrosome in interphase, spindle poles all stages mitosis, extremities midbody mam-malian (Potorous, human, Chinese hamster, mouse). This staining was...
It has been claimed repeatedly that gamma-tubulin is exclusively localized at the spindle poles in mitotic animal cells, where it plays a role microtubule nucleation. In addition to this localization, we have observed gamma-tubulin-specific staining of several cells (human, kangaroo rat, mouse, Chinese hamster, Xenopus and Drosophila) using five polyclonal antibodies raised against unique sequences four different fixation protocols. HeLa PtK2 was detected from late prometaphase telophase....
Oxidized low density lipoproteins (oxLDL) are thought to play a major role in atherosclerosis. OxLDL exhibit wide variety of biological effects resulting from their ability interfere with intracellular signaling. The cellular targets and primary signaling events oxLDL unknown. We report that elicit, intact cells, tyrosine phosphorylation the epithelial growth factor receptor (EGFR) activation its pathway. This triggered by was associated derivatization reactive amino groups EGFR mimicked...
TNF plays a dual, still enigmatic role in melanoma, either acting as cytotoxic cytokine or favoring tumorigenic inflammatory microenvironment. Herein, the tumor growth of melanoma cell lines expressing major histocompatibility complex class I molecules at high levels (MHC-I(high)) was dramatically impaired TNF-deficient mice, and this associated with enhanced tumor-infiltrating CD8(+) T lymphocytes. Immunodepletion CD8 cells fully restored TNF(-/-) mice. Systemic administration Etanercept...
The importance of post-translational geranylgeranylation the GTPase RhoA for its ability to induce cellular proliferation and malignant transformation is not well understood. In this manuscript we demonstrate that required proper localization V14RhoA actin stress fiber focal adhesion formation. Furthermore, was also suppressing p21<sup>WAF</sup> transcription, promoting cell cycle progression proliferation. focus formation enhance plating efficiency oncogenic Ras anchorage-dependent growth...
Nitrogen-containing bisphosphonates (N-BPs) have been designed to inhibit osteoclast-mediated bone resorption. However, it is now accepted that part of their anti-tumor activities related interference with the mevalonate pathway.We investigated effects zoledronic acid (ZOL), on cell proliferation and protein isoprenylation in two tumoral (LnCAP, PC-3,), one normal established (PNT1-A) prostatic line. To assess if inhibition geranyl-geranylation by ZOL impairs biological activity RhoA GTPase,...
Abstract Drug-tolerance has emerged as one of the major non-genetic adaptive processes driving resistance to targeted therapy (TT) in non-small cell lung cancer (NSCLC). However, kinetics and sequence molecular events governing this response remain poorly understood. Here, we combine real-time monitoring cell-cycle dynamics single-cell RNA sequencing a broad panel oncogenic addiction such EGFR-, ALK-, BRAF- KRAS-mutant NSCLC, treated with their corresponding TT. We identify common path drug...
Exposure of the skin to UVB light results in formation DNA photolesions that can give rise cell death, mutations, and onset carcinogenic events. Specific proteins are activated by then trigger signal transduction pathways lead cellular responses. An alteration these signaling molecules is thought be a fundamental event tumor promotion irradiation. RhoB, encoding small GTPase has been identified as damage-inducible gene. RhoB involved epidermal growth factor (EGF) receptor trafficking,...
Abstract Hypoxia is a crucial factor in tumor aggressiveness and resistance to treatment, particularly glioma. Our previous results have shown that inhibiting the small GTPase RhoB increased oxygenation of U87 human glioblastoma xenografts, part, by regulating angiogenesis. We investigated here whether might also control signaling pathway would permit glioma cells adapt hypoxia. first showed silencing with siRNA induced degradation inhibition transcriptional activity hypoxia-inducible...
Proliferation of vascular smooth muscle cells (SMC) is a hallmark in the pathogenesis atherosclerotic lesions. Mildly oxidized low density lipoproteins (UV-oxLDL), which are mitogenic to cultured AG-08133A SMC, activate sphingomyelin (SM)-ceramide pathway. We report here following. (i) UV-oxLDL elicited biphasic and sustained activation MBP kinase activity, phosphorylation nuclear translocation p44/42 mitogen-activated protein (MAPK), [<sup>3</sup>H]thymidine incorporation, were inhibited by...
Abstract —Nonesterified fatty acids (NEFAs) are acutely liberated during lipolysis and chronically elevated in pathological conditions, such as insulin resistance, hypertension, obesity, which known risk factors for atherosclerosis. The purpose of this study was to investigate the effect mechanism action NEFAs on epithelial growth factor (EGF) receptor (EGFR). In ECV-304 endothelial cell line, unsaturated triggered a time- dose-dependent tyrosine phosphorylation EGFR (polyunsaturated [PUFAs]...
Protein isoprenylation is a lipid posttranslational modification required for the function of many proteins that share carboxyl-terminal CAAX motif. The X residue determines which isoprenoid will be added to cysteine. When methionine or serine, farnesyl-transferase transfers farnesyl, and when leucine isoleucine, geranygeranyl-transferase I, geranylgeranyl group. But despite its CKVL motif, RhoB was reported both geranylgeranylated farnesylated. Thus, determinants prenylation appear more...
RhoB has been reported to exert positive and negative effects on cancer pathophysiology but an understanding of its role in breast remains incomplete. Analysis data from the Oncomine database showed a correlation between expression positivity for both estrogen receptor alpha (ERα) progesterone (PR). This finding was validated by our analysis tissue microarray constructed cohort 113 patients then investigated human cell models. We found that strongly correlated with ERα PR inversely tumor...
ABSTRACT The human Ras superfamily of small GTPases controls essential cellular processes such as gene expression and cell proliferation. As their deregulation is widely associated with cancer, regulatory proteins have become increasingly attractive for the development novel therapeutics. Classical methods to monitor GTPase activation include pulldown assays that limit analysis GTP-bound form from lysates. Alternatively, live-cell FRET biosensors may be used study dynamics in response...
The presence of γ-tubulin in microtubule preparations, obtained by disassembly/assembly cycles at 0°C/37°C from the brain several mammals, is demonstrated immunoblotting with specific antibodies directed against three distinct regions protein. In contrast was absent pure tubulin chromatography on phosphocellulose, but retained column other microtubule-associated proteins. A large part present cold stable material remaining after disassembly 0°C and partially solubilized using high salt, thus...
Rho GTPases have been implicated in the control of several cellular functions, including regulation actin cytoskeleton, cell proliferation, and oncogenesis. Unlike RhoA RhoC, RhoB localizes part to endosomes controls endocytic trafficking. Using a yeast two-hybrid screen glutathione S-transferase pulldown assay, we identified LC2, light chain microtubule-associated protein MAP1A, as novel binding partner for RhoB. GTP 18-amino acid C-terminal hypervariable domain are critical its MAP1A/LC2....
Abstract Background The Rho GTPases A, B and C proteins, members of the family whose activity is regulated by GDP/GTP cycling, function in many cellular pathways controlling proliferation have recently been implicated tumorigenesis. Although overexpression has correlated with tumorigenesis, only their GTP-bound forms are able to activate signalling Thus, focus much recent research identify biological tools capable quantifying level Rho, or determining subcellular location activation. However...
Ectopic Fas-ligand (FasL) expression in tumor cells is responsible for both escape through counterattack of Fas-positive infiltrating lymphocytes and rejection though inflammatory immune responses. We have previously shown that RhoA GTPase its effector ROCK negatively control FasL membrane murine melanoma B16F10 cells. In this study, we found treatment with the inhibitor H1152 reduced development vivo overexpression. Although did not reduce growth vitro, pretreatment delayed appearance,...
ABSTRACT Defective antitumor immune responses are frequent consequences of defects in the expression major histocompatibility complex (MHC) class I and costimulatory molecules. We demonstrated that statins, inhibitors HMGCoA reductase, enhance mIFN‐γ induced MHC antigens on murine B16F10 melanoma. GGTI‐298, a geranylgeranyl transferase inhibitor, but not FTI‐277, farnesyl mimics this effect statins. This is related to peptide transporter protein TAP1 up‐regulation. Simultaneously, GGTI‐298...
Small GTPases are highly regulated proteins that control essential signaling pathways through the activity of their effector proteins. Among RHOA subfamily, RHOB regulates peculiar functions could be associated with endocytic trafficking Here, we used an optimized assay based on tripartite split-GFP complementation to localize GTPase-effector complexes high-resolution. The detection interaction Rhotekin Rho binding domain (RBD) specifically recognizes active GTP-bound GTPase, is performed in...