References of "Chariot, Alain"
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See detailDBIRD complex integrates alternative mRNA splicing with RNA polymerase II transcript elongation
Close, Pierre ULg; East, Phil; Svejstrup, Barbara et al

in Nature (2012)

Alternative messenger RNA splicing is the main reason that vast mammalian proteomic complexity can be achieved with a limited number of genes. Splicing is physically and functionally coupled to ... [more ▼]

Alternative messenger RNA splicing is the main reason that vast mammalian proteomic complexity can be achieved with a limited number of genes. Splicing is physically and functionally coupled to transcription, and is greatly affected by the rate of transcript elongation1–3. As the nascent pre-mRNA emerges from transcribing RNA polymerase II (RNAPII), it is assembled into a messenger ribonucleoprotein (mRNP) particle; this is the functional form of the nascent pre-mRNA and determines the fate of the mature transcript4. However, factors that connect the transcribing polymerase with the mRNP particle and help to integrate transcript elongation with mRNA splicing remain unclear. Here we characterize the human interactome of chromatin-associated mRNP particles. This led us to identify deleted in breast cancer 1 (DBC1) and ZNF326 (which we call ZNF-protein interacting with nuclear mRNPs and DBC1 (ZIRD)) as subunits of a novel protein complex—named DBIRD—that binds directly to RNAPII. DBIRD regulates alternative splicing of a large set of exons embedded in (A 1 T)-rich DNA, and is present at the affected exons. RNAinterference- mediated DBIRD depletion results in region-specific decreases in transcript elongation, particularly across areas encompassing affected exons. Together, these data indicate that the DBIRD complex acts at the interface between mRNP particles and RNAPII, integrating transcript elongation with the regulation of alternative splicing. [less ▲]

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See detailDifferential usage of NF-kB activating signals by IL-1b and TNF-a in pancreatic beta cells
Ortis, Fernanda; Miani, M; Colli, ML et al

in FEBS Letters (2012), 586

The cytokines interleukin (IL)-1b and tumor necrosis factor (TNF)-a induce b-cell death in type 1 diabetes via NF-kB activation. IL-1b induces a more marked NF-kB activation than TNF-a, with higher ... [more ▼]

The cytokines interleukin (IL)-1b and tumor necrosis factor (TNF)-a induce b-cell death in type 1 diabetes via NF-kB activation. IL-1b induces a more marked NF-kB activation than TNF-a, with higher expression of genes involved in b-cell dysfunction and death. We show here a differential usage of the IKK complex by IL-1b and TNF-a in b-cells. While TNF-a uses IKK complexes containing both IKKa and IKKb, IL-1b induces complexes with IKKa only; this effect is achieved by induction of IKKb degradation via the proteasome. Both IKKg and activation of the TRAF6-TAK1-JNK pathway are involved in IL-1b-induced IKKb degradation. [less ▲]

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See detailp27(Kip1) Is a Microtubule-Associated Protein that Promotes Microtubule Polymerization during Neuron Migration.
Godin, Juliette ULg; Thomas, Noemie; Laguesse, Sophie ULg et al

in Developmental Cell (2012), 23(4), 729-44

The migration of cortical interneurons is characterized by extensive morphological changes that result from successive cycles of nucleokinesis and neurite branching. Their molecular bases remain elusive ... [more ▼]

The migration of cortical interneurons is characterized by extensive morphological changes that result from successive cycles of nucleokinesis and neurite branching. Their molecular bases remain elusive, and the present work describes how p27(Kip1) controls cell-cycle-unrelated signaling pathways to regulate these morphological remodelings. Live imaging reveals that interneurons lacking p27(Kip1) show delayed tangential migration resulting from defects in both nucleokinesis and dynamic branching of the leading process. At the molecular level, p27(Kip1) is a microtubule-associated protein that promotes polymerization of microtubules in extending neurites, thereby contributing to tangential migration. Furthermore, we show that p27(Kip1) controls actomyosin contractions that drive both forward translocation of the nucleus and growth cone splitting. Thus, p27(Kip1) cell-autonomously controls nucleokinesis and neurite branching by regulating both actin and microtubule cytoskeletons. [less ▲]

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See detailp27(Kip1) as a master regulator of cortical neuron migration.
Godin, Juliette ULg; Thomas, Noémie; Laguesse, Sophie ULg et al

Poster (2012)

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See detailp27(Kip1) as a master regulator of cortical neuron migration.
Godin, Juliette ULg; Thomas, Noémie; Laguesse, Sophie ULg et al

Poster (2012)

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See detailCortical interneurons tangential migration : p27(Kip1) as a novel master regulator.
Godin, Juliette ULg; Thomas, Noémie; Laguesse, Sophie ULg et al

Poster (2012)

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See detailInduction of the Alternative NF-{kappa}B Pathway by Lymphotoxin {alpha}{beta} (LT{alpha}{beta}) Relies on Internalization of LT{beta} Receptor
Ganeff, Corine; Remouchamps, Caroline ULg; Boutaffala, Layla et al

in Molecular & Cellular Biology (2011), 21

Several tumor necrosis factor receptor (TNFR) family members activate both the classical and the alternative NF-κB pathways. However, how a single receptor engages these two distinct pathways is still ... [more ▼]

Several tumor necrosis factor receptor (TNFR) family members activate both the classical and the alternative NF-κB pathways. However, how a single receptor engages these two distinct pathways is still poorly understood. Using lymphotoxin β receptor (LTβR) as a prototype, we showed that activation of the alternative, but not the classical, NF-κB pathway relied on internalization of the receptor. Further molecular analyses revealed a specific cytosolic region of LTβR essential for its internalization, TRAF3 recruitment, and p100 processing. Interestingly, we found that dynamin-dependent, but clathrin-independent, internalization of LTβR appeared to be required for the activation of the alternative, but not the classical, NF-κB pathway. In vivo, ligand-induced internalization of LTβR in mesenteric lymph node stromal cells correlated with induction of alternative NF-κB target genes. Thus, our data shed light on LTβR cellular trafficking as a process required for specific biological functions of NF-κB. [less ▲]

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See detailNF-kB, stem cells and breast cancer: the links get stronger
Shostak, Kateryna ULg; Chariot, Alain ULg

in Breast Cancer Research [=BCR] (2011), 13(4), 214

Self-renewing breast cancer stem cells are key actors in perpetuating tumour existence and in treatment resistance and relapse. The molecular pathways required for their maintenance are starting to be ... [more ▼]

Self-renewing breast cancer stem cells are key actors in perpetuating tumour existence and in treatment resistance and relapse. The molecular pathways required for their maintenance are starting to be elucidated. Among them is the transcription factor NF-κB, which is known to play critical roles in cell survival, inflammation and immunity. Recent studies indicate that mammary epithelial NF-κB regulates the self-renewal of breast cancer stem cells in a model of Her2-dependent tumourigenesis. We will describe here the NF-κB-activating pathways that are involved in this process and in which progenitor cells this transcription factor is actually activated. [less ▲]

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See detailp27(Kip1) as a master regulator of cortical neuron migration
Godin, Juliette ULg; Thomas, Noémie; Laguesse, Sophie ULg et al

Scientific conference (2011, June)

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See detailInvolvement of placental growth factor in Wallerian degeneration
Chaballe, Linda ULg; Close, Pierre ULg; SEMPELS, Maxime ULg et al

in Glia (2011), 59(3), 379-396

Wallerian degeneration (WD) is an inflammatory process of nerve degeneration, which occurs more rapidly in the peripheral nervous system compared with the central nervous system, resulting, respectively ... [more ▼]

Wallerian degeneration (WD) is an inflammatory process of nerve degeneration, which occurs more rapidly in the peripheral nervous system compared with the central nervous system, resulting, respectively in successful and aborted axon regeneration. In the peripheral nervous system, Schwann cells (SCs) and macrophages, under the control of a network of cytokines and chemokines, represent the main cell types involved in this process. Within this network, the role of placental growth factor (PlGF) remains totally unknown. However, properties like monocyte activation/attraction, ability to increase expression of pro-inflammatory molecules, as well as neuroprotective effects, make it a candidate likely implicated in this process. Also, nothing is described about the expression and localization of this molecule in the peripheral nervous system. To address these original questions, we decided to study PlGF expression under physiological and degenerative conditions and to explore its role in WD, using a model of sciatic nerve transection in wild-type and Pgf(-/-) mice. Our data show dynamic changes of PlGF expression, from periaxonal in normal nerve to SCs 24h postinjury, in parallel with a p65/NF-κB recruitment on Pgf promoter. After injury, SC proliferation is reduced by 30% in absence of PlGF. Macrophage invasion is significantly delayed in Pgf(-/-) mice compared with wild-type mice, which results in worse functional recovery. MCP-1 and proMMP-9 exhibit a 3-fold reduction of their relative expressions in Pgf(-/-) injured nerves, as demonstrated by cytokine array. In conclusion, this work originally describes PlGF as a novel member of the cytokine network of WD. [less ▲]

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See detailInvolvement of Placental growth factor in Wallerian degeneration
Chaballe, Linda ULg; Close, Pierre ULg; Sempels, Maxime ULg et al

Poster (2010, September)

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See detailThe repressing function of the oncoprotein BCL-3 requires CtBP while its polyubiquitination and degradation involve the E3 ligase TBLR1
Keutgens, Aurore ULg; Shostak, Kateryna ULg; Close, Pierre ULg et al

in Molecular & Cellular Biology (2010), 30

The nuclear and oncogenic BCL-3 protein activates or represses gene transcription when bound to NF-kB proteins p50 and p52, yet the molecules that specifically interact with BCL-3 and drive BCL-3-mediated ... [more ▼]

The nuclear and oncogenic BCL-3 protein activates or represses gene transcription when bound to NF-kB proteins p50 and p52, yet the molecules that specifically interact with BCL-3 and drive BCL-3-mediated effects on gene expression remain largely uncharacterized. Moreover, GSK3-mediated phosphorylation of BCL-3 triggers its degradation through the proteasome, but the proteins involved in this degradative pathway are poorly characterized. Biochemical purification of interacting partners of BCL-3 led to the identification of CtBP as a molecule required for the ability of BCL-3 to repress gene transcription. CtBP is also required for the oncogenic potential of BCL-3 and for its ability to inhibit UV-mediated cell apoptosis in keratinocytes. We also defined the E3 ligase TBLR1 as a protein involved in BCL-3 degradation through a GSK3-independent pathway. Thus, our data demonstrate that the LSD1/CtBP complex is required for the repressing abilities of an oncogenic IkB protein, and they establish a functional link between the E3 ligase TBLR1 and NF-kB. [less ▲]

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See detailThe emerging role of lysine acetylation of non-nuclear proteins
Close, Pierre ULg; Creppe, Catherine; Gillard, Magali ULg et al

in Cellular and Molecular Life Sciences : CMLS (2010), 67(8), 1255-1264

Lysine acetylation is a post-translational modification that critically regulates gene transcription by targeting histones as well as a variety of transcription factors in the nucleus. More recent reports ... [more ▼]

Lysine acetylation is a post-translational modification that critically regulates gene transcription by targeting histones as well as a variety of transcription factors in the nucleus. More recent reports have also demonstrated that numerous proteins located outside the nucleus are also acetylated and that this modification has profound consequences on their functions. This review describes the latest findings on the substrates acetylated outside the nucleus and on the acetylases and deacetylates that catalyse these modifications. Protein acetylation is emerging as a major mechanism by which key proteins are regulated in many physiological processes such as migration, metabolism and aging as well as in pathological circumstances such as cancer and neurodegenerative disorders. [less ▲]

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See detailElongator orchestrates cerebral cortical neurogenesis
creppe, catherine; malinouskaya, lina; Volvert, Marie-Laure ULg et al

in Medecine Sciences : M/S (2010)

Pas d'abstract pour cette publication

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See detailTNFL–Induced p100 processing (TIPP) relies on the internalization of the cognate TNFR
Ganeff, Corinne; Galopin, Géraldine; Remouchamps, Caroline ULg et al

Conference (2010, January)

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See detailElongator - an emerging role in neurological disorders
Nguyen, Laurent ULg; Humbert, Sandrine; Saudou, Frédéric et al

in Trends in Molecular Medicine (2010), 16

We are currently facing important challenges to prevent and cure neurological disorders that are becoming a major public health issue in our aging society. Because of the lack of mechanism-based ... [more ▼]

We are currently facing important challenges to prevent and cure neurological disorders that are becoming a major public health issue in our aging society. Because of the lack of mechanism-based treatments to correct brain malformations or to prevent the progression of cell death in neurodegenerative disorders, most of these pathologies follow a fatal course. Thus, one major objective is to understand the molecular events that underlie these diseases in order to prevent their onset and/or halt their progression. Converging experimental and clinical evidences obtained by our lab and others prompt us to speculate that Elongator may be commonly targeted in different neurological disorders and as such, should represent a strong candidate for research and development efforts to design drug-based therapies. [less ▲]

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See detailMolecular Layers underlying cytoskeletal remodelling during cortical development
Heng, J.; Chariot, Alain ULg; Nguyen, Laurent

in Trends in Neurosciences (2010), 33

During neural development, the cytoskeleton of newborn neurons is subjected to extensive and dynamic remodelling to facilitate the sequential steps of neurogenesis, cell migration and terminal ... [more ▼]

During neural development, the cytoskeleton of newborn neurons is subjected to extensive and dynamic remodelling to facilitate the sequential steps of neurogenesis, cell migration and terminal differentiation. As we begin to elucidate the molecular mechanisms which precipitate these functions, it is clear that while common factors may be required, different configurations of the cytoskeleton prefigure the correct execution of each step, such that we can define cohorts of proteins whose functions are indispensable for the control of neuronal migration but not terminal differentiation. It has also emerged that these combinatorial protein functions are predetermined by regulated gene expression, as well as precise subcellular localisation of their protein products. We present this view in the context of recent striking data on how the cytoskeleton is regulated during the maturation of cortical neurons within the developing brain. [less ▲]

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See detailSHIP-1 inhibits CD95/APO-1/Fas-induced apoptosis in primary T lymphocytes and T leukemic cells by promoting CD95 glycosylation independently of its phosphatase activity
Charlier, Edith ULg; Condé, Claude ULg; Zhang, Jing et al

in Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K (2010)

SHIP-1 functions as a negative regulator of immune responses by hydrolyzing phosphatidylinositol-3,4,5-triphosphate generated by PI 3-kinase activity. As a result, SHIP-1 deficiency in mice results in ... [more ▼]

SHIP-1 functions as a negative regulator of immune responses by hydrolyzing phosphatidylinositol-3,4,5-triphosphate generated by PI 3-kinase activity. As a result, SHIP-1 deficiency in mice results in myeloproliferation and B cell lymphoma. On the other hand, SHIP-1 deficient mice have a reduced T cell population, but the underlying mechanisms are unknown. In this work, we hypothesized that SHIP-1 plays anti-apoptotic functions in T cells upon stimulation of the death receptor CD95/APO-1/Fas. Using primary T cells from SHIP-1-/- mice and T leukemic cell lines, we report here that SHIP-1 is a potent inhibitor of CD95-induced death. We observed that a small fraction of the SHIP-1 pool is localized to the endoplasmic reticulum where it promotes CD95 glycosylation. This post-translational modification requires an intact SH2 domain of SHIP-1, but is independent of its phosphatase activity. The glycosylated CD95 fails to oligomerize upon stimulation, resulting in impaired DISC formation and downstream apoptotic cascade. These results uncover an unanticipated inhibitory function for SHIP-1 and emphasize the role of glycosylation in the regulation of CD95 signaling in T cells. This work may also provide a new basis for therapeutic strategies using compounds inducing apoptosis through the CD95 pathway on SHIP-1 negative leukemic T cells. [less ▲]

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See detailMolecular layers underlying cytoskeletal remodelling during cortcial development
Heng, Julian; Chariot, Alain ULg; Nguyen, Laurent ULg

in Trends in Neurosciences (2010)

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