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

Author

Listed:
  • Bandish Kapadia

    (University of Maryland)

  • Nahid M. Nanaji

    (Maryland Healthcare System
    University of Maryland Medical Center)

  • Kavita Bhalla

    (University of Maryland)

  • Binny Bhandary

    (University of Maryland)

  • Rena Lapidus

    (University of Maryland)

  • Afshin Beheshti

    (Molecular Oncology Research Institute, Tufts Medical Center)

  • Andrew M. Evens

    (Molecular Oncology Research Institute, Tufts Medical Center)

  • Ronald B. Gartenhaus

    (University of Maryland
    Veterans Administration Medical Center)

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.

Suggested Citation

  • Bandish Kapadia & Nahid M. Nanaji & Kavita Bhalla & Binny Bhandary & Rena Lapidus & Afshin Beheshti & Andrew M. Evens & Ronald B. Gartenhaus, 2018. "Fatty Acid Synthase induced S6Kinase facilitates USP11-eIF4B complex formation for sustained oncogenic translation in DLBCL," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03028-y
    DOI: 10.1038/s41467-018-03028-y
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    Cited by:

    1. Maria Pilar Sanchez-Bailon & Soo-Youn Choi & Elizabeth R. Dufficy & Karan Sharma & Gavin S. McNee & Emma Gunnell & Kelly Chiang & Debashish Sahay & Sarah Maslen & Grant S. Stewart & J. Mark Skehel & I, 2021. "Arginine methylation and ubiquitylation crosstalk controls DNA end-resection and homologous recombination repair," Nature Communications, Nature, vol. 12(1), pages 1-18, December.

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