Laboratoire de Spectrométrie de Masse Protéomique (LSMP)

Publications

Année de publication : 2018

Forget Antoine, Martignetti Loredana, Puget Stéphanie, Calzone Laurence, Brabetz Sebastian, Picard Daniel, Montagud Arnau, Liva Stéphane, Sta Alexandre, Dingli Florent, Arras Guillaume, Rivera Jaime, Loew Damarys, Besnard Aurore, Lacombe Joëlle, Pagès Mélanie, Varlet Pascale, Dufour Christelle, Yu Hua, L. Mercier Audrey, Indersie Emilie, Chivet Anaïs, Leboucher Sophie, Sieber Laura, Beccaria Kevin, Gombert Michael, D. Meyer Frauke, Qin Nan, Bartl Jasmin, Chavez Lukas, Okonechnikov Konstantin, Sharma Tanvi, Thatikonda Venu, Bourdeaut Franck, Pouponnot Celio, Ramaswamy Vijay, Korshunov Andrey, Borkhardt Arndt, Reifenberger Guido, Poullet Patrick, D. Taylor Michael, Kool Marcel, M. Pfister Stefan, Kawauchi Daisuke, Barillot Emmanuel, Remke Marc, Ayrault Olivier (2018 Sep 10)

Aberrant ERBB4-SRC Signaling as a Hallmark of Group 4 Medulloblastoma Revealed by Integrative Phosphoproteomic Profiling

Cancer Cell : 34 : 379-395 : DOI : 10.1016/j.ccell.2018.08.002 En savoir plus
Résumé

The current consensus recognizes four main medulloblastoma subgroups (wingless, Sonic hedgehog, group 3 and group 4). While medulloblastoma subgroups have been characterized extensively at the (epi-)genomic and transcriptomic levels, the proteome and phosphoproteome landscape remain to be comprehensively elucidated. Using quantitative (phospho)-proteomics in primary human medulloblastomas, we unravel distinct posttranscriptional regulation leading to highly divergent oncogenic signaling and kinase activity profiles in groups 3 and 4 medulloblastomas. Specifically, proteomic and phosphoproteomic analyses identify aberrant ERBB4-SRC signaling in group 4. Hence, enforced expression of an activated SRC combined with p53 inactivation induces murine tumors that resemble group 4 medulloblastoma. Therefore, our integrative proteogenomics approach unveils an oncogenic pathway and potential therapeutic vulnerability in the most common medulloblastoma subgroup.

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Nassrallah Amr, Rougée Martin, Bourbousse Clara, Drevensek Stephanie, Fonseca Sandra, Iniesto Elisa, Ait-Mohamed Ouardia, Deton-Cabanillas Anne-Flore, Zabulon Gerald, Ahmed Ikhlak, Stroebel David, Masson Vanessa, Lombard Berangere, Eeckhout Dominique, Gevaert Kris, Loew Damarys, Genovesio Auguste, Breyton Cecile, de Jaeger Geert, Bowler Chris, Rubio Vicente, Barneche Fredy (2018 Sep 7)

DET1-mediated degradation of a SAGA-like deubiquitination module controls H2Bub homeostasis

eLIFE : DOI : 10.7554/eLife.37892 En savoir plus
Résumé

DE-ETIOLATED 1 (DET1) is an evolutionarily conserved component of the ubiquitination machinery that mediates the destabilization of key regulators of cell differentiation and proliferation in multicellular organisms. In this study, we provide evidence from Arabidopsis that DET1 is essential for the regulation of histone H2B monoubiquitination (H2Bub) over most genes by controlling the stability of a deubiquitination module (DUBm). In contrast with yeast and metazoan DUB modules that are associated with the large SAGA complex, the Arabidopsis DUBm only comprises three proteins (hereafter named SGF11, ENY2 and UBP22) and appears to act independently as a major H2Bub deubiquitinase activity. Our study further unveils that DET1-DDB1-Associated-1 (DDA1) protein interacts with SGF11 in vivo, linking the DET1 complex to light-dependent ubiquitin-mediated proteolytic degradation of the DUBm. Collectively, these findings uncover a signaling path controlling DUBm availability, potentially adjusting H2Bub turnover capacity to the cell transcriptional status

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Verweij Frederik J, Revenu Celine, Arras Guillaume, Dingli Florent, Loew Damarys, Follain Gautier, Allio Guillaume, Goetz Jacky G., Herbomel Philippe, Del Bene Filippo, Raposo Graça, van Niel Guillaume (2018 Jul 30)

Live tracking of inter-organ communication by endogenous exosomes in vivo

BioRxiv : DOI : 10.1101/380311 En savoir plus
Résumé

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Laencina Laura, Dubois Violaine, Le Moigne Vincent , Viljoen Albertus, Majlessi Laleh, Pritchard Justin, Bernut Audrey, Piel Laura, Roux Anne-Laure, Gaillard Jean-Louis, Lombard Bérengère, Loew Damarys, Rubin Eric J., Brosch Roland, Kremer Laurent, Herrmann Jean-Louis and Girard-Misguich Fabienne (2018 Jan 17)

Identification of genes required for Mycobacterium abscessus growth in vivo with a prominent role of the ESX-4 locus

Proceedings of the National Academy of Sciences of the United States of America : 115 : E1002-E1011 : DOI : 10.1073/pnas.1713195115 En savoir plus
Résumé

The coevolution of mycobacteria and amoebae seems to have contributed to shaping the virulence of nontuberculous mycobacteria in macrophages. We identified a pool of genes essential for the intracellular survival of Mycobacterium abscessus inside amoebae and macrophages and discovered a hot spot of transposon insertions within the orthologous ESX-4 T7SS locus. We generated a mutant with the deletion of a structural key ESX component, EccB4. We demonstrate rupture of the phagosomal membrane only in the presence of an intact eccB4 gene. These results suggest an unanticipated role of ESX-4 T7SS in governing the intracellular behavior of a mycobacterium. Because M. abscessus lacks ESX-1, it is tempting to speculate that ESX-4 operates as a surrogate for ESX-1 in M. tuberculosis.

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