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    Fatty Acid Synthase induced S6Kinase facilitates USP11-eIF4B complex formation for sustained oncogenic translation in DLBCL

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    Author
    Nanaji, N.M.
    Bhalla, K.
    Kapadia, Bandish
    Date
    2018
    Journal
    Nature Communications
    Publisher
    Nature Publishing Group
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://dx.doi.org/10.1038/s41467-018-03028-y
    Abstract
    Altered lipid metabolism and aberrant protein translation are strongly associated with cancerous outgrowth; however, the inter-regulation of these key processes is still underexplored in diffuse large B-cell lymphoma (DLBCL). Although fatty acid synthase (FASN) activity is reported to positively correlate with PI3K-Akt-mTOR pathway that can modulate protein synthesis, the precise impact of FASN inhibition on this process is still unknown. Herein, we demonstrate that attenuating FASN expression or its activity significantly reduces eIF4B (eukaryotic initiation factor 4B) levels and consequently overall protein translation. Through biochemical studies, we identified eIF4B as a bonafide substrate of USP11, which stabilizes and enhances eIF4B activity. Employing both pharmacological and genetic approaches, we establish that FASN-induced PI3K-S6Kinase signaling phosphorylates USP11 enhancing its interaction with eIF4B and thereby promoting oncogenic translation. Copyright 2018 The Author(s).
    Sponsors
    This work was supported in part by a Merit Review Award from the Department of Veterans Affairs (R.B.G.), and R01CA164311 (R.B.G) from the National Institutes of Health.
    Keyword
    Carcinogenesis--chemistry
    Carcinogenesis--metabolism
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85043256026&doi=10.1038%2fs41467-018-03028-y&partnerID=40&md5=c99735f593b63afd2934642739077d95; http://hdl.handle.net/10713/9281
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41467-018-03028-y
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