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2011
Bianco Alberto, Kostarelos Kostas, Prato Maurizio
Making carbon nanotubes biocompatible and biodegradable Article de journal
Dans: Chemical Communications (Cambridge, England), vol. 47, non 37, p. 10182–10188, 2011, ISSN: 1364-548X.
Résumé | Liens | BibTeX | Étiquettes: Animals, Biocompatible, carbon, Coated Materials, HeLa Cells, Humans, I2CT, nanotechnology, Nanotubes, Team-Bianco
@article{bianco_making_2011,
title = {Making carbon nanotubes biocompatible and biodegradable},
author = {Alberto Bianco and Kostas Kostarelos and Maurizio Prato},
doi = {10.1039/c1cc13011k},
issn = {1364-548X},
year = {2011},
date = {2011-10-01},
journal = {Chemical Communications (Cambridge, England)},
volume = {47},
number = {37},
pages = {10182--10188},
abstract = {Carbon nanotubes are promising nanomaterials with great potential in the field of nanomedicine for both therapeutic and diagnostic applications. Different approaches have been developed to render this material biocompatible and to modulate any ensuing toxic effects. In the context of medical use, although chemically functionalised carbon nanotubes display reduced toxicity, they are still considered with scepticism due to their perceived non-biodegradability. Recently, it has been demonstrated that functionalised carbon nanotubes can be degraded by oxidative enzymes. This finding is offering a new perspective for the development of carbon nanotubes in medicine. This article highlights recent advances that can act as paradigm-shifts towards the design of biocompatible and biodegradable functionalised carbon nanotubes and allow their translation into the clinic.},
keywords = {Animals, Biocompatible, carbon, Coated Materials, HeLa Cells, Humans, I2CT, nanotechnology, Nanotubes, Team-Bianco},
pubstate = {published},
tppubtype = {article}
}
Carbon nanotubes are promising nanomaterials with great potential in the field of nanomedicine for both therapeutic and diagnostic applications. Different approaches have been developed to render this material biocompatible and to modulate any ensuing toxic effects. In the context of medical use, although chemically functionalised carbon nanotubes display reduced toxicity, they are still considered with scepticism due to their perceived non-biodegradability. Recently, it has been demonstrated that functionalised carbon nanotubes can be degraded by oxidative enzymes. This finding is offering a new perspective for the development of carbon nanotubes in medicine. This article highlights recent advances that can act as paradigm-shifts towards the design of biocompatible and biodegradable functionalised carbon nanotubes and allow their translation into the clinic.
Eleftherianos Ioannis, Won Sungyong, Chtarbanova Stanislava, Squiban Barbara, Ocorr Karen, Bodmer Rolf, Beutler Bruce, Hoffmann Jules A, Imler Jean-Luc
ATP-sensitive potassium channel (K(ATP))-dependent regulation of cardiotropic viral infections Article de journal
Dans: Proceedings of the National Academy of Sciences of the United States of America, vol. 108, non 29, p. 12024–12029, 2011, ISSN: 1091-6490.
Résumé | Liens | BibTeX | Étiquettes: Animals, Heart, HeLa Cells, hoffmann, Humans, imler, Immunity, Immunoblotting, Inbred C57BL, Innate, KATP Channels, M3i, Mice, Nodaviridae, Pinacidil, Reverse Transcriptase Polymerase Chain Reaction, RNA Interference, Tolbutamide, Viral Load, Viremia
@article{eleftherianos_atp-sensitive_2011,
title = {ATP-sensitive potassium channel (K(ATP))-dependent regulation of cardiotropic viral infections},
author = {Ioannis Eleftherianos and Sungyong Won and Stanislava Chtarbanova and Barbara Squiban and Karen Ocorr and Rolf Bodmer and Bruce Beutler and Jules A Hoffmann and Jean-Luc Imler},
doi = {10.1073/pnas.1108926108},
issn = {1091-6490},
year = {2011},
date = {2011-07-01},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {108},
number = {29},
pages = {12024--12029},
abstract = {The effects of the cellular environment on innate immunity remain poorly characterized. Here, we show that in Drosophila ATP-sensitive potassium channels (K(ATP)) mediate resistance to a cardiotropic RNA virus, Flock House virus (FHV). FHV viral load in the heart rapidly increases in K(ATP) mutant flies, leading to increased viremia and accelerated death. The effect of K(ATP) channels is dependent on the RNA interference genes Dcr-2, AGO2, and r2d2, indicating that an activity associated with this potassium channel participates in this antiviral pathway in Drosophila. Flies treated with the K(ATP) agonist drug pinacidil are protected against FHV infection, thus demonstrating the importance of this regulation of innate immunity by the cellular environment in the heart. In mice, the Coxsackievirus B3 replicates to higher titers in the hearts of mayday mutant animals, which are deficient in the Kir6.1 subunit of K(ATP) channels, than in controls. Together, our data suggest that K(ATP) channel deregulation can have a critical impact on innate antiviral immunity in the heart.},
keywords = {Animals, Heart, HeLa Cells, hoffmann, Humans, imler, Immunity, Immunoblotting, Inbred C57BL, Innate, KATP Channels, M3i, Mice, Nodaviridae, Pinacidil, Reverse Transcriptase Polymerase Chain Reaction, RNA Interference, Tolbutamide, Viral Load, Viremia},
pubstate = {published},
tppubtype = {article}
}
The effects of the cellular environment on innate immunity remain poorly characterized. Here, we show that in Drosophila ATP-sensitive potassium channels (K(ATP)) mediate resistance to a cardiotropic RNA virus, Flock House virus (FHV). FHV viral load in the heart rapidly increases in K(ATP) mutant flies, leading to increased viremia and accelerated death. The effect of K(ATP) channels is dependent on the RNA interference genes Dcr-2, AGO2, and r2d2, indicating that an activity associated with this potassium channel participates in this antiviral pathway in Drosophila. Flies treated with the K(ATP) agonist drug pinacidil are protected against FHV infection, thus demonstrating the importance of this regulation of innate immunity by the cellular environment in the heart. In mice, the Coxsackievirus B3 replicates to higher titers in the hearts of mayday mutant animals, which are deficient in the Kir6.1 subunit of K(ATP) channels, than in controls. Together, our data suggest that K(ATP) channel deregulation can have a critical impact on innate antiviral immunity in the heart.
Canard B, Vachon H, Fontaine T, Pin J J, Paul S, Genin C, Mueller C G
Generation of anti-DC-SIGN monoclonal antibodies capable of blocking HIV-1 gp120 binding and reactive on formalin-fixed tissue Article de journal
Dans: Immunol.Lett., vol. 135, non 1879-0542 (Electronic), p. 165–172, 2011.
Résumé | BibTeX | Étiquettes: Adhesion, adhesion molecules, Animals, Antibodies, antibody, Antigen, Antigens, Blocking, C-Type, C-type lectin, CD, Cell Adhesion, Cell Adhesion Molecules, Cell Surface, Chemistry, clones, Dendritic Cells, DERMIS, Differentiation, Fixatives, Formaldehyde, formalin-fixed tissue, Genetics, GLYCOPROTEIN, GP120, HeLa Cells, HIV, HIV Envelope Protein gp120, HIV-1, Human, Humans, hybridoma, ICAM-3, immunodeficiency, Immunology, Inbred BALB C, infection, LECTIN, Lectins, Macrophage, Macrophages, Mice, Monoclonal, monoclonal antibody, MONOCLONAL-ANTIBODY, Monocytes, Murine-Derived, Myelomonocytic, Nih 3T3 Cells, Paraffin Embedding, pathogenicity, Protein, Receptor, Receptors, recognition, Skin, Team-Mueller, virus
@article{canard_generation_2011,
title = {Generation of anti-DC-SIGN monoclonal antibodies capable of blocking HIV-1 gp120 binding and reactive on formalin-fixed tissue},
author = {B Canard and H Vachon and T Fontaine and J J Pin and S Paul and C Genin and C G Mueller},
year = {2011},
date = {2011-01-01},
journal = {Immunol.Lett.},
volume = {135},
number = {1879-0542 (Electronic)},
pages = {165--172},
abstract = {DC-SIGN is a C-type lectin of recognized importance in immunology and in the pathogenicity human pathogens. Monoclonal antibodies directed against DC-SIGN have been generated, but their systemic characterization for interfering with binding of the HIV-1 glycoprotein 120 has often been omitted. Moreover, so far, no anti-DC-SIGN monoclonal antibody has been described that recognizes its antigen after formalin fixation and paraffin embedding. In this study, we have generated new anti-DC-SIGN monoclonal antibodies using HeLa cells stably expressing DC-SIGN as immunogen. We have obtained 11 hybridoma clones producing antibodies that recognized DC-SIGN on monocyte-derived dendritic cells and on dermal-type macrophages. Seven monoclonal antibodies displayed a capacity to interfere with DC-SIGN binding to HIV-1 gp120. One recognized DC-SIGN on formalin-fixed dendritic cells and macrophages. Using this antibody we have obtained specific labelling of DC-SIGN and colocalisation with the dermal macrophage marker CD163 on human skin. The described monoclonal anti-human DC-SIGN antibodies will be of use to the scientific community to address fundamental immunology issues, in particular concerning macrophages and dendritic cells, and help elucidate infection events of pathogen targeting DC-SIGN as recognition receptor},
keywords = {Adhesion, adhesion molecules, Animals, Antibodies, antibody, Antigen, Antigens, Blocking, C-Type, C-type lectin, CD, Cell Adhesion, Cell Adhesion Molecules, Cell Surface, Chemistry, clones, Dendritic Cells, DERMIS, Differentiation, Fixatives, Formaldehyde, formalin-fixed tissue, Genetics, GLYCOPROTEIN, GP120, HeLa Cells, HIV, HIV Envelope Protein gp120, HIV-1, Human, Humans, hybridoma, ICAM-3, immunodeficiency, Immunology, Inbred BALB C, infection, LECTIN, Lectins, Macrophage, Macrophages, Mice, Monoclonal, monoclonal antibody, MONOCLONAL-ANTIBODY, Monocytes, Murine-Derived, Myelomonocytic, Nih 3T3 Cells, Paraffin Embedding, pathogenicity, Protein, Receptor, Receptors, recognition, Skin, Team-Mueller, virus},
pubstate = {published},
tppubtype = {article}
}
DC-SIGN is a C-type lectin of recognized importance in immunology and in the pathogenicity human pathogens. Monoclonal antibodies directed against DC-SIGN have been generated, but their systemic characterization for interfering with binding of the HIV-1 glycoprotein 120 has often been omitted. Moreover, so far, no anti-DC-SIGN monoclonal antibody has been described that recognizes its antigen after formalin fixation and paraffin embedding. In this study, we have generated new anti-DC-SIGN monoclonal antibodies using HeLa cells stably expressing DC-SIGN as immunogen. We have obtained 11 hybridoma clones producing antibodies that recognized DC-SIGN on monocyte-derived dendritic cells and on dermal-type macrophages. Seven monoclonal antibodies displayed a capacity to interfere with DC-SIGN binding to HIV-1 gp120. One recognized DC-SIGN on formalin-fixed dendritic cells and macrophages. Using this antibody we have obtained specific labelling of DC-SIGN and colocalisation with the dermal macrophage marker CD163 on human skin. The described monoclonal anti-human DC-SIGN antibodies will be of use to the scientific community to address fundamental immunology issues, in particular concerning macrophages and dendritic cells, and help elucidate infection events of pathogen targeting DC-SIGN as recognition receptor
2010
Al-Jamal Khuloud T, Toma Francesca M, Yilmazer Açelya, Ali-Boucetta Hanene, Nunes Antonio, Herrero Maria-Antonia, Tian Bowen, Eddaoudi Ayad, Eddaoui Ayad, Al-Jamal Wafa' T, Bianco Alberto, Prato Maurizio, Kostarelo Kostas
Enhanced cellular internalization and gene silencing with a series of cationic dendron-multiwalled carbon nanotube:siRNA complexes Article de journal
Dans: FASEB journal: official publication of the Federation of American Societies for Experimental Biology, vol. 24, non 11, p. 4354–4365, 2010, ISSN: 1530-6860.
Résumé | Liens | BibTeX | Étiquettes: Biological Transport, carbon, Cations, Cell Line, Cell Survival, Gene Silencing, HeLa Cells, Humans, I2CT, Models, Molecular, Nanotubes, RNA, Small Interfering, Team-Bianco, Transfection, tumor
@article{al-jamal_enhanced_2010,
title = {Enhanced cellular internalization and gene silencing with a series of cationic dendron-multiwalled carbon nanotube:siRNA complexes},
author = {Khuloud T Al-Jamal and Francesca M Toma and Açelya Yilmazer and Hanene Ali-Boucetta and Antonio Nunes and Maria-Antonia Herrero and Bowen Tian and Ayad Eddaoudi and Ayad Eddaoui and Wafa' T Al-Jamal and Alberto Bianco and Maurizio Prato and Kostas Kostarelo},
doi = {10.1096/fj.09-141036},
issn = {1530-6860},
year = {2010},
date = {2010-11-01},
journal = {FASEB journal: official publication of the Federation of American Societies for Experimental Biology},
volume = {24},
number = {11},
pages = {4354--4365},
abstract = {One of the major obstacles to the clinical development of gene silencing by small interfering RNA (siRNA) is its effective cytoplasmic delivery. Carbon nanotubes have been proposed as novel nanomaterials that can offer significant advantages for the intracellular delivery of nucleic acids, such as siRNA. We recently demonstrated in a proof-of-principle study that amino-functionalized multiwalled carbon nanotubes (f-MWNT) can effectively deliver in vivo an siRNA sequence, triggering cell apoptosis that results in human lung xenograft eradication and prolonged survival. In the present study, we demonstrate how a newly synthesized series of polycationic dendron-MWNT constructs with a precisely tailored number of amino functions (dendron generations) can complex and effectively deliver double-stranded siRNA to achieve gene silencing in vitro. A systematic comparison between the f-MWNT series in terms of cellular uptake, cytotoxicity, and siRNA complexation is offered. Significant improvement in siRNA delivery with the dendron-MWNT conjugates is shown, and gene silencing was obtained in 2 human cell lines using 2 different siRNA sequences. The study reveals that through f-MWNT structure-biological function analysis novel nanotube-based siRNA transfer vectors can be designed with minimal cytotoxicity and effective delivery and gene-silencing capabilities.},
keywords = {Biological Transport, carbon, Cations, Cell Line, Cell Survival, Gene Silencing, HeLa Cells, Humans, I2CT, Models, Molecular, Nanotubes, RNA, Small Interfering, Team-Bianco, Transfection, tumor},
pubstate = {published},
tppubtype = {article}
}
One of the major obstacles to the clinical development of gene silencing by small interfering RNA (siRNA) is its effective cytoplasmic delivery. Carbon nanotubes have been proposed as novel nanomaterials that can offer significant advantages for the intracellular delivery of nucleic acids, such as siRNA. We recently demonstrated in a proof-of-principle study that amino-functionalized multiwalled carbon nanotubes (f-MWNT) can effectively deliver in vivo an siRNA sequence, triggering cell apoptosis that results in human lung xenograft eradication and prolonged survival. In the present study, we demonstrate how a newly synthesized series of polycationic dendron-MWNT constructs with a precisely tailored number of amino functions (dendron generations) can complex and effectively deliver double-stranded siRNA to achieve gene silencing in vitro. A systematic comparison between the f-MWNT series in terms of cellular uptake, cytotoxicity, and siRNA complexation is offered. Significant improvement in siRNA delivery with the dendron-MWNT conjugates is shown, and gene silencing was obtained in 2 human cell lines using 2 different siRNA sequences. The study reveals that through f-MWNT structure-biological function analysis novel nanotube-based siRNA transfer vectors can be designed with minimal cytotoxicity and effective delivery and gene-silencing capabilities.
2009
Herrero Antonia M, Toma Francesca M, Al-Jamal Khuloud T, Kostarelos Kostas, Bianco Alberto, Ros Tatiana Da, Bano Fouzia, Casalis Loredana, Scoles Giacinto, Prato Maurizio
Synthesis and characterization of a carbon nanotube-dendron series for efficient siRNA delivery Article de journal
Dans: Journal of the American Chemical Society, vol. 131, non 28, p. 9843–9848, 2009, ISSN: 1520-5126.
Résumé | Liens | BibTeX | Étiquettes: Acrylates, Animals, Azo Compounds, Biological Transport, carbon, Cytoplasm, Dendrimers, Drug Carriers, Ethylenediamines, Gene Silencing, HeLa Cells, Humans, I2CT, Nanotubes, Polyamines, RNA, Small Interfering, Solubility, Team-Bianco, Thiosemicarbazones, Transfection, water
@article{herrero_synthesis_2009,
title = {Synthesis and characterization of a carbon nanotube-dendron series for efficient siRNA delivery},
author = {Antonia M Herrero and Francesca M Toma and Khuloud T Al-Jamal and Kostas Kostarelos and Alberto Bianco and Tatiana Da Ros and Fouzia Bano and Loredana Casalis and Giacinto Scoles and Maurizio Prato},
doi = {10.1021/ja903316z},
issn = {1520-5126},
year = {2009},
date = {2009-07-01},
journal = {Journal of the American Chemical Society},
volume = {131},
number = {28},
pages = {9843--9848},
abstract = {A new series of dendron-functionalized multiwalled carbon nanotube (MWNT) derivatives, characterized by the presence of numerous positively charged tetraalkyl ammonium salts at the periphery of the dendron, has been synthesized. The positive charges on the MWNT surface, coupled with the unique ability of carbon nanotubes (CNTs) to penetrate cell membranes, make the new derivatives potentially ideal vectors for siRNA delivery. Using a fluorescently labeled, noncoding siRNA sequence, we demonstrate that cytoplasmic delivery of the nucleic acid is remarkably increased throughout the different dendron generations. The work reported here highlights the fact that dendron-functionalized CNTs can be rationally designed as efficient carriers of siRNA that can eventually lead to gene silencing.},
keywords = {Acrylates, Animals, Azo Compounds, Biological Transport, carbon, Cytoplasm, Dendrimers, Drug Carriers, Ethylenediamines, Gene Silencing, HeLa Cells, Humans, I2CT, Nanotubes, Polyamines, RNA, Small Interfering, Solubility, Team-Bianco, Thiosemicarbazones, Transfection, water},
pubstate = {published},
tppubtype = {article}
}
A new series of dendron-functionalized multiwalled carbon nanotube (MWNT) derivatives, characterized by the presence of numerous positively charged tetraalkyl ammonium salts at the periphery of the dendron, has been synthesized. The positive charges on the MWNT surface, coupled with the unique ability of carbon nanotubes (CNTs) to penetrate cell membranes, make the new derivatives potentially ideal vectors for siRNA delivery. Using a fluorescently labeled, noncoding siRNA sequence, we demonstrate that cytoplasmic delivery of the nucleic acid is remarkably increased throughout the different dendron generations. The work reported here highlights the fact that dendron-functionalized CNTs can be rationally designed as efficient carriers of siRNA that can eventually lead to gene silencing.
2008
Goulev Youlian, Fauny Jean Daniel, Gonzalez-Marti Beatriz, Flagiello Domenico, Silber Joël, Zider Alain
SCALLOPED interacts with YORKIE, the nuclear effector of the hippo tumor-suppressor pathway in Drosophila Article de journal
Dans: Current Biology: CB, vol. 18, non 6, p. 435–441, 2008, ISSN: 0960-9822.
Résumé | Liens | BibTeX | Étiquettes: Animals, Cell Proliferation, Drosophila, Drosophila Proteins, HeLa Cells, Humans, I2CT, Imagerie, Intracellular Signaling Peptides and Proteins, Morphogenesis, Nuclear Proteins, Protein Kinases, Protein-Serine-Threonine Kinases, Signal Transduction, Trans-Activators, Transcription Factors, Tumor Suppressor Proteins, Wing
@article{goulev_scalloped_2008,
title = {SCALLOPED interacts with YORKIE, the nuclear effector of the hippo tumor-suppressor pathway in Drosophila},
author = {Youlian Goulev and Jean Daniel Fauny and Beatriz Gonzalez-Marti and Domenico Flagiello and Joël Silber and Alain Zider},
url = {http://www.ncbi.nlm.nih.gov/pubmed/18313299},
doi = {10.1016/j.cub.2008.02.034},
issn = {0960-9822},
year = {2008},
date = {2008-01-01},
urldate = {2011-10-24},
journal = {Current Biology: CB},
volume = {18},
number = {6},
pages = {435--441},
abstract = {In Drosophila, SCALLOPED (SD) belongs to a family of evolutionarily conserved proteins characterized by the presence of a TEA/ATTS DNA-binding domain [1, 2]. SD physically interacts with the product of the vestigial (vg) gene, where the dimer functions as a master gene controlling wing formation [3, 4]. The VG-SD dimer activates the transcription of several specific wing genes, including sd and vg themselves [5, 6]. The dimer drives cell-cycle progression by inducing expression of the dE2F1 transcription factor [7], which regulates genes involved in DNA replication and cell-cycle progression. Recently, YORKIE (YKI) was identified as a transcriptional coactivator that is the downstream effector of the Hippo signaling pathway, which controls cell proliferation and apoptosis in Drosophila[8]. We identified SD as a partner for YKI. We show that interaction between YKI and SD increases SD transcriptional activity both ex vivo in Drosophila S2 cells and in vivo in Drosophila wing discs and promotes YKI nuclear localization. We also show that YKI overexpression induces vg and dE2F1 expression and that proliferation induced by YKI or by a dominant-negative form of FAT in wing disc is significantly reduced in a sd hypomorphic mutant context. Contrary to YKI, SD is not required in all imaginal tissues. This indicates that YKI-SD interaction acts in a tissue-specific fashion and that other YKI partners must exist.},
keywords = {Animals, Cell Proliferation, Drosophila, Drosophila Proteins, HeLa Cells, Humans, I2CT, Imagerie, Intracellular Signaling Peptides and Proteins, Morphogenesis, Nuclear Proteins, Protein Kinases, Protein-Serine-Threonine Kinases, Signal Transduction, Trans-Activators, Transcription Factors, Tumor Suppressor Proteins, Wing},
pubstate = {published},
tppubtype = {article}
}
In Drosophila, SCALLOPED (SD) belongs to a family of evolutionarily conserved proteins characterized by the presence of a TEA/ATTS DNA-binding domain [1, 2]. SD physically interacts with the product of the vestigial (vg) gene, where the dimer functions as a master gene controlling wing formation [3, 4]. The VG-SD dimer activates the transcription of several specific wing genes, including sd and vg themselves [5, 6]. The dimer drives cell-cycle progression by inducing expression of the dE2F1 transcription factor [7], which regulates genes involved in DNA replication and cell-cycle progression. Recently, YORKIE (YKI) was identified as a transcriptional coactivator that is the downstream effector of the Hippo signaling pathway, which controls cell proliferation and apoptosis in Drosophila[8]. We identified SD as a partner for YKI. We show that interaction between YKI and SD increases SD transcriptional activity both ex vivo in Drosophila S2 cells and in vivo in Drosophila wing discs and promotes YKI nuclear localization. We also show that YKI overexpression induces vg and dE2F1 expression and that proliferation induced by YKI or by a dominant-negative form of FAT in wing disc is significantly reduced in a sd hypomorphic mutant context. Contrary to YKI, SD is not required in all imaginal tissues. This indicates that YKI-SD interaction acts in a tissue-specific fashion and that other YKI partners must exist.
Dieker J, Cisterna B, Monneaux F, Decossas M, van der Vlag J, Biggiogera M, Muller S
Apoptosis-linked changes in the phosphorylation status and subcellular localization of the spliceosomal autoantigen U1-70K Article de journal
Dans: Cell Death and Differentiation, vol. 15, non 4, p. 793–804, 2008, ISSN: 1350-9047.
Résumé | Liens | BibTeX | Étiquettes: Apoptosis, Autoantigens, Autoimmunity, Caspase 3, Chromatin, HeLa Cells, Humans, I2CT, Jurkat Cells, Lupus Erythematosus, Monneaux, Phosphorylation, Post-Translational, Protein Phosphatase 1, Protein Processing, Protein Transport, Recombinant Proteins, Ribonucleoprotein, RNA Splicing, Serine, Spliceosomes, Systemic, Team-Dumortier, Time Factors, U1 Small Nuclear
@article{dieker_apoptosis-linked_2008,
title = {Apoptosis-linked changes in the phosphorylation status and subcellular localization of the spliceosomal autoantigen U1-70K},
author = {J Dieker and B Cisterna and F Monneaux and M Decossas and J van der Vlag and M Biggiogera and S Muller},
doi = {10.1038/sj.cdd.4402312},
issn = {1350-9047},
year = {2008},
date = {2008-01-01},
journal = {Cell Death and Differentiation},
volume = {15},
number = {4},
pages = {793--804},
abstract = {Apoptosis consists of highly regulated pathways involving post-translational modifications and cleavage of proteins leading to sequential inactivation of the main cellular processes. Here, we focused on the apoptotic processing of one of the essential components of the mRNA splicing machinery, the U1-70K snRNP protein. We found that at an early stage of apoptosis, before the cleavage of the C-terminal part of the protein by caspase-3, the basal phosphorylation of the Ser140 residue located within the RNA recognition motif, increases very significantly. A caspase-dependent, PP1-mediated dephosphorylation of other serine residues takes place in a subset of U1-70K proteins. The U1-70K protein phosphorylated at Ser140 is clustered in heterogeneous ectopic RNP-derived structures, which are finally extruded in apoptotic bodies. The elaborate processing of the spliceosomal U1-70K protein we identified might play an important role in the regulated breakdown of the mRNA splicing machinery during early apoptosis. In addition, these specific changes in the phosphorylation/dephosphorylation balance and the subcellular localization of the U1-70K protein might explain why the region encompassing the Ser140 residue becomes a central autoantigen during the autoimmune disease systemic lupus erythematosus.},
keywords = {Apoptosis, Autoantigens, Autoimmunity, Caspase 3, Chromatin, HeLa Cells, Humans, I2CT, Jurkat Cells, Lupus Erythematosus, Monneaux, Phosphorylation, Post-Translational, Protein Phosphatase 1, Protein Processing, Protein Transport, Recombinant Proteins, Ribonucleoprotein, RNA Splicing, Serine, Spliceosomes, Systemic, Team-Dumortier, Time Factors, U1 Small Nuclear},
pubstate = {published},
tppubtype = {article}
}
Apoptosis consists of highly regulated pathways involving post-translational modifications and cleavage of proteins leading to sequential inactivation of the main cellular processes. Here, we focused on the apoptotic processing of one of the essential components of the mRNA splicing machinery, the U1-70K snRNP protein. We found that at an early stage of apoptosis, before the cleavage of the C-terminal part of the protein by caspase-3, the basal phosphorylation of the Ser140 residue located within the RNA recognition motif, increases very significantly. A caspase-dependent, PP1-mediated dephosphorylation of other serine residues takes place in a subset of U1-70K proteins. The U1-70K protein phosphorylated at Ser140 is clustered in heterogeneous ectopic RNP-derived structures, which are finally extruded in apoptotic bodies. The elaborate processing of the spliceosomal U1-70K protein we identified might play an important role in the regulated breakdown of the mRNA splicing machinery during early apoptosis. In addition, these specific changes in the phosphorylation/dephosphorylation balance and the subcellular localization of the U1-70K protein might explain why the region encompassing the Ser140 residue becomes a central autoantigen during the autoimmune disease systemic lupus erythematosus.
2005
Bianco Alberto, Kostarelos Kostas, Prato Maurizio
Applications of carbon nanotubes in drug delivery Article de journal
Dans: Current Opinion in Chemical Biology, vol. 9, non 6, p. 674–679, 2005, ISSN: 1367-5931.
Résumé | Liens | BibTeX | Étiquettes: Biological, carbon, Drug Delivery Systems, Electron, HeLa Cells, Humans, I2CT, Microscopy, Models, Nanotubes, Nucleic Acids, Peptides, scanning, Team-Bianco
@article{bianco_applications_2005,
title = {Applications of carbon nanotubes in drug delivery},
author = {Alberto Bianco and Kostas Kostarelos and Maurizio Prato},
doi = {10.1016/j.cbpa.2005.10.005},
issn = {1367-5931},
year = {2005},
date = {2005-12-01},
journal = {Current Opinion in Chemical Biology},
volume = {9},
number = {6},
pages = {674--679},
abstract = {The development of new and efficient drug delivery systems is of fundamental importance to improve the pharmacological profiles of many classes of therapeutic molecules. Many different types of drug delivery systems are currently available. Within the family of nanomaterials, carbon nanotubes (CNT) have emerged as a new alternative and efficient tool for transporting and translocating therapeutic molecules. CNT can be functionalised with bioactive peptides, proteins, nucleic acids and drugs, and used to deliver their cargos to cells and organs. Because functionalised CNT display low toxicity and are not immunogenic, such systems hold great potential in the field of nanobiotechnology and nanomedicine.},
keywords = {Biological, carbon, Drug Delivery Systems, Electron, HeLa Cells, Humans, I2CT, Microscopy, Models, Nanotubes, Nucleic Acids, Peptides, scanning, Team-Bianco},
pubstate = {published},
tppubtype = {article}
}
The development of new and efficient drug delivery systems is of fundamental importance to improve the pharmacological profiles of many classes of therapeutic molecules. Many different types of drug delivery systems are currently available. Within the family of nanomaterials, carbon nanotubes (CNT) have emerged as a new alternative and efficient tool for transporting and translocating therapeutic molecules. CNT can be functionalised with bioactive peptides, proteins, nucleic acids and drugs, and used to deliver their cargos to cells and organs. Because functionalised CNT display low toxicity and are not immunogenic, such systems hold great potential in the field of nanobiotechnology and nanomedicine.
1998
Dumortier H, Gunnewiek J Klein, Roussel J P, van Aarssen Y, Briand J P, van Venrooij W J, Muller S
Dans: Nucleic Acids Research, vol. 26, non 23, p. 5486–5491, 1998, ISSN: 0305-1048.
Résumé | Liens | BibTeX | Étiquettes: Amino Acid Sequence, Animals, Dumortier, HeLa Cells, Humans, I2CT, Molecular Sequence Data, Peptide Fragments, Protein Binding, Rabbits, Ribonucleoprotein, Ribonucleoproteins, Small Nuclear, Solutions, Spliceosomes, Team-Dumortier, U1 Small Nuclear, Zinc, Zinc Fingers
@article{dumortier_at_1998,
title = {At least three linear regions but not the zinc-finger domain of U1C protein are exposed at the surface of the protein in solution and on the human spliceosomal U1 snRNP particle},
author = {H Dumortier and J Klein Gunnewiek and J P Roussel and Y van Aarssen and J P Briand and W J van Venrooij and S Muller},
doi = {10.1093/nar/26.23.5486},
issn = {0305-1048},
year = {1998},
date = {1998-12-01},
journal = {Nucleic Acids Research},
volume = {26},
number = {23},
pages = {5486--5491},
abstract = {No structural information on U1C protein either in its free state or bound to the spliceosomal U1 small nuclear ribonucleoprotein (snRNP) particle is currently available. Using rabbit antibodies raised against a complete set of 15 U1C overlapping synthetic peptides (16-30 residues long) in different immunochemical tests, linear regions exposed at the surface of free and U1 snRNP-bound U1C were identified. Epitopes within at least three regions spanning residues 31-62, 85-103 and 116-159 were recognized on free and plastic-immobilized recombinant human U1C expressed in Escherichia coli, on in vitro translated U1C protein and on U1C bound to the U1 snRNP particle present in HeLa S100 extract. Using a zinc affinity labeling method, we further showed that the N-terminal U1C peptide containing a zinc-finger motif (peptide 5-34) effectively binds65Zn2+. The N-terminal region of U1C, which is functional in U1 snRNP assembly, is apparently not located at the surface of the U1 snRNP particle.},
keywords = {Amino Acid Sequence, Animals, Dumortier, HeLa Cells, Humans, I2CT, Molecular Sequence Data, Peptide Fragments, Protein Binding, Rabbits, Ribonucleoprotein, Ribonucleoproteins, Small Nuclear, Solutions, Spliceosomes, Team-Dumortier, U1 Small Nuclear, Zinc, Zinc Fingers},
pubstate = {published},
tppubtype = {article}
}
No structural information on U1C protein either in its free state or bound to the spliceosomal U1 small nuclear ribonucleoprotein (snRNP) particle is currently available. Using rabbit antibodies raised against a complete set of 15 U1C overlapping synthetic peptides (16-30 residues long) in different immunochemical tests, linear regions exposed at the surface of free and U1 snRNP-bound U1C were identified. Epitopes within at least three regions spanning residues 31-62, 85-103 and 116-159 were recognized on free and plastic-immobilized recombinant human U1C expressed in Escherichia coli, on in vitro translated U1C protein and on U1C bound to the U1 snRNP particle present in HeLa S100 extract. Using a zinc affinity labeling method, we further showed that the N-terminal U1C peptide containing a zinc-finger motif (peptide 5-34) effectively binds65Zn2+. The N-terminal region of U1C, which is functional in U1 snRNP assembly, is apparently not located at the surface of the U1 snRNP particle.
Hoet R M, Raats J M, de Wildt R, Dumortier H, Muller S, van den Hoogen F, van Venrooij W J
Dans: Molecular Immunology, vol. 35, non 16, p. 1045–1055, 1998, ISSN: 0161-5890.
Résumé | Liens | BibTeX | Étiquettes: Amino Acid Sequence, Antibodies, Autoantibodies, Cross Reactions, Dumortier, Epitope Mapping, Genes, HeLa Cells, Humans, I2CT, Immunoglobulin, Immunoglobulin Fragments, Immunoglobulin Variable Region, Immunohistochemistry, Lupus Erythematosus, Monoclonal, Ribonucleoprotein, Ribonucleoproteins, Small Nuclear, Systemic, Team-Dumortier, U1 Small Nuclear
@article{hoet_human_1998,
title = {Human monoclonal autoantibody fragments from combinatorial antibody libraries directed to the U1snRNP associated U1C protein; epitope mapping, immunolocalization and V-gene usage},
author = {R M Hoet and J M Raats and R de Wildt and H Dumortier and S Muller and F van den Hoogen and W J van Venrooij},
doi = {10.1016/s0161-5890(98)00093-5},
issn = {0161-5890},
year = {1998},
date = {1998-11-01},
journal = {Molecular Immunology},
volume = {35},
number = {16},
pages = {1045--1055},
abstract = {To study the localization and function of the U1snRNP associated U1C protein, so far only human sera from systemic lupus erythematosus (SLE) overlap syndrome patients have been used. Here we report for the first time the isolation of human monoclonal anti-UIC autoantibody fragments from IgG derived combinatorial and semi-synthetic human antibody libraries. Two classes of human monoclonal anti-UIC (auto)antibodies were found: specific anti-U1C autoantibodies, recognizing U1C only, and cross-reactive antibodies which also react with U1A and Sm-B/B'proteins. The heavy chains (V(H)genes) of all five antibodies from the semi-synthetic libraries and two of the three U1C-specific patient derived autoantibody fragments are encoded by V(H)3 genes, in which V(H) 3-30 (DP-49) was overrepresented. The heavy chain of the two cross-reactive autoantibodies are derived from the 3-07 (DP-54) gene. Three epitope regions on the U1C protein are targeted by these antibodies. (1) Four U1C specific antibodies recognize an N-terminal region of U1C in which amino acids 30-63 are essential for recognition, (2) two antibodies recognize only the complete U1C protein, and (3) two cross-reactive and one U1C specific antibody recognize the C-terminal domain in which amino acids 98-126 are critical for recognition. The two cross-reactive antibodies (K 11 and K 15) recognize the proline-rich region of the U1C protein (amino acids 98 126) and cross-react with proline-rich regions in Sm-B/B' (amino acids 163-184) and U1A (amino acids 187-204). All 10 antibody fragments are able to immunoprecipitate the native U1snRNP particle. The two cross-reactive antibodies immunoprecipitate the other Sm containing snRNPs as well. Using confocal immunofluorescence microscopy we could show that the major part of the U1C protein is localized within the coiled body structure.},
keywords = {Amino Acid Sequence, Antibodies, Autoantibodies, Cross Reactions, Dumortier, Epitope Mapping, Genes, HeLa Cells, Humans, I2CT, Immunoglobulin, Immunoglobulin Fragments, Immunoglobulin Variable Region, Immunohistochemistry, Lupus Erythematosus, Monoclonal, Ribonucleoprotein, Ribonucleoproteins, Small Nuclear, Systemic, Team-Dumortier, U1 Small Nuclear},
pubstate = {published},
tppubtype = {article}
}
To study the localization and function of the U1snRNP associated U1C protein, so far only human sera from systemic lupus erythematosus (SLE) overlap syndrome patients have been used. Here we report for the first time the isolation of human monoclonal anti-UIC autoantibody fragments from IgG derived combinatorial and semi-synthetic human antibody libraries. Two classes of human monoclonal anti-UIC (auto)antibodies were found: specific anti-U1C autoantibodies, recognizing U1C only, and cross-reactive antibodies which also react with U1A and Sm-B/B'proteins. The heavy chains (V(H)genes) of all five antibodies from the semi-synthetic libraries and two of the three U1C-specific patient derived autoantibody fragments are encoded by V(H)3 genes, in which V(H) 3-30 (DP-49) was overrepresented. The heavy chain of the two cross-reactive autoantibodies are derived from the 3-07 (DP-54) gene. Three epitope regions on the U1C protein are targeted by these antibodies. (1) Four U1C specific antibodies recognize an N-terminal region of U1C in which amino acids 30-63 are essential for recognition, (2) two antibodies recognize only the complete U1C protein, and (3) two cross-reactive and one U1C specific antibody recognize the C-terminal domain in which amino acids 98-126 are critical for recognition. The two cross-reactive antibodies (K 11 and K 15) recognize the proline-rich region of the U1C protein (amino acids 98 126) and cross-react with proline-rich regions in Sm-B/B' (amino acids 163-184) and U1A (amino acids 187-204). All 10 antibody fragments are able to immunoprecipitate the native U1snRNP particle. The two cross-reactive antibodies immunoprecipitate the other Sm containing snRNPs as well. Using confocal immunofluorescence microscopy we could show that the major part of the U1C protein is localized within the coiled body structure.
1990
Schröter H, Mueller C G, Meese K, Nordheim A
Synergism in ternary complex formation between the dimeric glycoprotein p67SRF, polypeptide p62TCF and the c-fos serum response element Article de journal
Dans: The EMBO journal, vol. 9, non 4, p. 1123–1130, 1990, ISSN: 0261-4189.
Résumé | BibTeX | Étiquettes: Base Sequence, Chloroquine, Gene Expression Regulation, Genetic, Glycosylation, HeLa Cells, Humans, Kinetics, Macromolecular Substances, Molecular Sequence Data, Nuclear Proteins, Oligonucleotide Probes, Plasmids, Polymerase Chain Reaction, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-fos, Proto-Oncogenes, Serum Response Factor, Team-Mueller, Transcription, Transcription Factors
@article{schroter_synergism_1990,
title = {Synergism in ternary complex formation between the dimeric glycoprotein p67SRF, polypeptide p62TCF and the c-fos serum response element},
author = {H Schröter and C G Mueller and K Meese and A Nordheim},
issn = {0261-4189},
year = {1990},
date = {1990-04-01},
journal = {The EMBO journal},
volume = {9},
number = {4},
pages = {1123--1130},
abstract = {Transcriptional regulation of the c-fos proto-oncogene requires the serum response element (SRE) which is complexed by a multi-protein assembly observed both in vitro and in vivo. Two protein factors, p67SRF and p62TCF (previously called p62), are required to interact with the SRE for efficient induction of c-fos by serum. By quantitative band shift electrophoresis we measure at least a 50-fold increase in SRE affinity for p67SRF/p62TCF over p67SRF alone. Stoichiometrically we determine that the ternary complex with p62TCF involves p67SRF in dimeric form. We demonstrate that p67SRF is a glycosylated nuclear transcription factor carrying terminal N-acetylglucosamine (GlcNAc) as a post-translational modification. A proteolytic limit digestion product, approximately 13 kd in size, was generated from the p67SRF-SRE complex. This p67SRF-core domain binds SRE, can dimerize with p67SRF and is still able to form a ternary complex with p62TCF. Therefore, three functional activities can be ascribed to this small p67SRF-core domain: specific DNA binding, dimerization and interaction with p62TCF. We demonstrate that these functions map within the p67SRF core fragment containing the region between amino acids 93 and 222.},
keywords = {Base Sequence, Chloroquine, Gene Expression Regulation, Genetic, Glycosylation, HeLa Cells, Humans, Kinetics, Macromolecular Substances, Molecular Sequence Data, Nuclear Proteins, Oligonucleotide Probes, Plasmids, Polymerase Chain Reaction, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-fos, Proto-Oncogenes, Serum Response Factor, Team-Mueller, Transcription, Transcription Factors},
pubstate = {published},
tppubtype = {article}
}
Transcriptional regulation of the c-fos proto-oncogene requires the serum response element (SRE) which is complexed by a multi-protein assembly observed both in vitro and in vivo. Two protein factors, p67SRF and p62TCF (previously called p62), are required to interact with the SRE for efficient induction of c-fos by serum. By quantitative band shift electrophoresis we measure at least a 50-fold increase in SRE affinity for p67SRF/p62TCF over p67SRF alone. Stoichiometrically we determine that the ternary complex with p62TCF involves p67SRF in dimeric form. We demonstrate that p67SRF is a glycosylated nuclear transcription factor carrying terminal N-acetylglucosamine (GlcNAc) as a post-translational modification. A proteolytic limit digestion product, approximately 13 kd in size, was generated from the p67SRF-SRE complex. This p67SRF-core domain binds SRE, can dimerize with p67SRF and is still able to form a ternary complex with p62TCF. Therefore, three functional activities can be ascribed to this small p67SRF-core domain: specific DNA binding, dimerization and interaction with p62TCF. We demonstrate that these functions map within the p67SRF core fragment containing the region between amino acids 93 and 222.
