A5011122889- Hedgehog Signaling Pathway Studies
- Drug Transport and Resistance Mechanisms
- Epigenetics and DNA Methylation
- Amino Acid Enzymes and Metabolism
- Cancer-related Molecular Pathways
- Lipid Membrane Structure and Behavior
- Bacterial Genetics and Biotechnology
- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- Photosynthetic Processes and Mechanisms
- Congenital Ear and Nasal Anomalies
- Electrochemical Analysis and Applications
- Monoclonal and Polyclonal Antibodies Research
- Glioma Diagnosis and Treatment
- Metalloenzymes and iron-sulfur proteins
- Genetics and Neurodevelopmental Disorders
- Receptor Mechanisms and Signaling
- Developmental Biology and Gene Regulation
- Chemical Synthesis and Analysis
- Genomic variations and chromosomal abnormalities
- Photoreceptor and optogenetics research
- DNA and Nucleic Acid Chemistry
- Oral and Maxillofacial Pathology
- Genomics and Chromatin Dynamics
- Microtubule and mitosis dynamics
Institut de Pharmacologie Moléculaire et Cellulaire
2012-2022
Centre National de la Recherche Scientifique
2010-2022
Université Côte d'Azur
2010-2022
Observatoire de la Côte d’Azur
2010-2021
Fondation Sophia Antipolis
2018
Inserm
2012
Infection et inflammation
2012
Institut de Biologie Valrose
2009
Laboratoire de physiologie cellulaire et moléculaire
2002-2006
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
1995-2000
Background Sonic hedgehog (Shh) signaling plays a crucial role in growth and patterning during embryonic development, also stem cell maintenance tissue regeneration adults. Aberrant Shh pathway activation is involved the development of many tumors, one most affected steps found these tumors regulation receptor Smoothened by Patched. In present work, we investigated Patched activity mechanism which inhibits Smoothened. Methodology/Principal Findings Using well-known Shh-responding line mouse...
Mixed protein-surfactant micelles are used for in vitro studies and 3D crystallization when solutions of pure, monodisperse integral membrane proteins required. However, many undergo inactivation transferred from the biomembrane into conventional surfactants with alkyl chains as hydrophobic moieties. Here we describe development rigid, saturated or aromatic hydrocarbon groups parts. Their stabilizing properties demonstrated three different proteins. The temperature at which 50% binding sites...
Further insight into the cosubstrate-induced structural change of melibiose permease (MelB) Escherichia coli has been sought by investigating binding and spectroscopic properties fluorescent sugar 2′-(N-5-dimethylaminonaphthalene-1-sulfonyl)aminoethyl 1-thio-β-d-galactopyranoside (Dns2-S-Gal) related analogs (Dns3-S-Gal or Dns6-S-Gal with a propyl hexyl instead an ethyl linker, respectively) interacting MelB in membrane vesicles proteoliposomes. The three efficiently inhibit transport bind...
Most anticancer drugs fail to eradicate tumors, leading the development of drug resistance and disease recurrence. The Hedgehog signaling plays a crucial role during embryonic development, but is also involved in cancer progression, metastasis. receptor Patched (Ptc) target gene that overexpressed many cells. Here, we show link between Ptc chemotherapy, provide new insight into function. cleared from plasma membrane upon interaction with its ligand Hedgehog, or treatment cells antagonist...
The nature of the axial ligands a heme group is an important factor in maintaining oxidation-reduction potential c-type cytochrome. Cytochrome c3 from Desulfovibrio vulgaris Hildenborough contains four bis-histidinyl coordinated hemes with low potentials. Site-directed mutagenesis was used to generate mutant which histidine 70, sixth ligand 4, has been replaced by methionine. protein expressed desulfuricans G200 at level similar wild type A model for three-dimensional structure D. cytochrome...
In the accompanying paper, we demonstrated presence of a fluorescence resonance energy transfer (FRET) between tryptophans melibiose permease (MelB) Escherichia coli and fluorescent sugar, 2′-(N-5-dimethylaminonaphthalene-1-sulfonyl)aminoethyl-1-thio-β-d-galactopyranoside (Dns2-S-Gal) bound at sugar-binding site (Maehrel, C., Cordat, E., Mus-Veteau, I., Leblanc, G. (1998) J. Biol. Chem. 273, 33192–33197). To identify that their to analyzed FRET properties MelB mutants carrying replacement...
// Laura Fiorini 1 , Marie-Aude Tribalat 2 Lucy Sauvard 1, Julie Cazareth Enzo Lalli Isabelle Broutin 3 Olivier P. Thomas 2, 4 Mus-Veteau Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275, Université Nice Sophia Antipolis, CNRS, Valbonne, France Chimie Nice, 7272, Faculté des Sciences, Laboratoire Cristallographie RMN Biologiques, 8015, CNRS - Faculte Pharmacie, Paris, Méditerranéen Biodiversité d'Ecologie Marine Continentale, 7263, IRD, Aix-Marseille, Avignon, Station d'Endoume,...
One of the crucial challenges in clinical management cancer is resistance to chemotherapeutics. We recently demonstrated that Hedgehog receptor Patched, which overexpressed many recurrent and metastatic cancers, a multidrug transporter for chemotherapeutic agents such as doxorubicin. The present work provides evidences Patched expressed adrenocortical carcinoma (ACC) patients, major player doxorubicin efflux human ACC cell line H295R. discovered methiothepin inhibits activity Patched. This...
Tryptophan fluorescence spectroscopy has been used to investigate the effects of sugars and coupling cations (H+, Na+, or Li+) on conformational properties purified melibiose permease after reconstitution in liposomes. Melibiose emission is selectively enhanced by sugars, which serve as substrates for symport reaction, alpha-galactosides producing larger variations (13-17%) than beta-galactosides (7%). Moreover, sugar-dependent increase specifically potentiated NaCl LiCl (5-7 times), are...
Background Alteration of functional regenerative properties parenchymal lung fibroblasts is widely proposed as a pathogenic mechanism for chronic obstructive pulmonary disease (COPD). However, what these functions are and how they impaired in COPD remain poorly understood. Apart from the role producing extracellular matrix, recent studies organs different suggest that such cells might contribute to repair processes by acting like mesenchymal stem cells. In addition, several reports sustain...
We previously reported that methiothepin, a small molecule known as nonselective serotonin 5-HT receptor antagonist, inhibited the doxorubicin efflux activity of Hedgehog Ptch1 and enhanced cytotoxic, pro-apoptotic, anti-proliferative, anti-clonogenic effects on adrenocortical carcinoma cells. Here, we show methiothepin also inhibits increases cytotoxicity in melanoma cells which endogenously overexpress Ptch1. Melanoma patients having BRAFV600E mutation are treated with vemurafenib, an...
Binding of the coupling ion (Na+ or Li+) and sugars to purified melibiose permease Escherichia coli, reconstituted in proteoliposomes, produces selective cooperative changes transporter tryptophan fluorescence. To assess individual contribution N- C-terminal domains these substrate-induced fluorescence variations, we replaced two tryptophans located its half (W299 W342) by a phenylalanine compared signal change mutants wild-type permease. None mutations significantly impairs transport...
To improve the structural organization model of melibiose permease, we assessed individual contributions N-terminal tryptophans to transporter fluorescence variations induced by binding cations and beta-configured sugars, replacement six phenylalanines study signal changes. Only two mutations, W116F located in helix IV W128F cytoplasmic loop 4-5, impair permease activity. The intrinsic spectroscopy analysis other mutants suggests that W54, II, W116, W128 are mostly responsible for...
In humans, dysfunctions of the Hedgehog receptors Patched and Smoothened are responsible for numerous pathologies. However, signaling mechanisms involving these less well characterized in mammals than Drosophila. To obtain structure-function relationship information on human Smoothened, we expressed Drosophila Schneider 2 cells. We show here that, as its counterpart, is able to repress pathway absence ligand. response Hedgehog, release inhibition, suggesting that a functional state also...
Melanoma patients harboring the BRAFV600E mutation are treated with vemurafenib. Almost all of them ultimately acquire resistance, leading to disease progression. Here, we find that a small molecule from marine sponge, panicein A hydroquinone (PAH), overcomes resistance melanoma cells vemurafenib, tumor elimination in corresponding human xenograft models mice. We report synthesis PAH and demonstrate this compound inhibits drug efflux activity Hedgehog receptor, Patched. Our SAR study allowed...