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    Inhibition of Ubc13-mediated ubiquitination by GPS2 regulates multiple stages of B cell development

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    License
    Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
    Date Issued
    2016-12-30
    Publisher Version
    10.1074/jbc.M116.755132
    Author(s)
    Lentucci, Claudia
    Belkina, Anna C.
    Cederquist, Carly T.
    Chan, Michelle
    Johnson, Holly E.
    Prasad, Sherry
    Lopacinski, Amanda
    Nikolajczyk, Barbara S.
    Monti, Stefano
    Snyder-Cappione, Jennifer
    Tanasa, Bogdan
    Cardamone, M. Dafne
    Perissi, Valentina
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    Permanent Link
    https://hdl.handle.net/2144/27020
    Citation (published version)
    Claudia Lentucci, Anna C. Belkina, Carly T. Cederquist, Michelle Chan, Holly E. Johnson, Sherry Prasad, Amanda Lopacinski, Barbara S. Nikolajczyk, Stefano Monti , Jennifer Snyder-Cappione, Bogdan Tanasa, M. Dafne Cardamone, and Valentina Perissi. Inhibition of Ubc13-mediated ubiquitination by GPS2 regulates multiple stages of B cell development. J. Biol. Chem. 2017 292: 2754-. doi:10.1074/jbc.M116.755132
    Abstract
    Non-proteolytic ubiquitin signaling mediated by Lys63 ubiquitin chains plays a critical role in multiple pathways that are key to the development and activation of immune cells. Our previous work indicates that GPS2 (G-protein Pathway Suppressor 2) is a multifunctional protein regulating TNF signaling and lipid metabolism in the adipose tissue through modulation of Lys63 ubiquitination events. However, the full extent of GPS2-mediated regulation of ubiquitination and the underlying molecular mechanisms are unknown. Here, we report that GPS2 is required for restricting the activation of TLR and BCR signaling pathways and the AKT/FOXO1 pathway in immune cells based on direct inhibition of Ubc13 enzymatic activity. Relevance of this regulatory strategy is confirmed in vivo by B cell-targeted deletion of GPS2, resulting in developmental defects at multiple stages of B cell differentiation. Together, these findings reveal that GPS2 genomic and non-genomic functions are critical for the development and cellular homeostasis of B cells.
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    Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
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    • Flow Cytometry Core Facility Papers [13]


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