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Med. Sci. 2018, 6(2), 41;

Myc, Oncogenic Protein Translation, and the Role of Polyamines

Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Author to whom correspondence should be addressed.
Received: 9 April 2018 / Revised: 19 May 2018 / Accepted: 22 May 2018 / Published: 25 May 2018
(This article belongs to the Special Issue Polyamine Metabolism in Disease and Polyamine-Targeted Therapies)
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Deregulated protein synthesis is a common feature of cancer cells, with many oncogenic signaling pathways directly augmenting protein translation to support the biomass needs of proliferating tissues. MYC’s ability to drive oncogenesis is a consequence of its essential role as a governor linking cell cycle entry with the requisite increase in protein synthetic capacity, among other biomass needs. To date, direct pharmacologic inhibition of MYC has proven difficult, but targeting oncogenic signaling modules downstream of MYC, such as the protein synthetic machinery, may provide a viable therapeutic strategy. Polyamines are essential cations found in nearly all living organisms that have both direct and indirect roles in the control of protein synthesis. Polyamine metabolism is coordinately regulated by MYC to increase polyamines in proliferative tissues, and this is further augmented in the many cancer cells harboring hyperactivated MYC. In this review, we discuss MYC-driven regulation of polyamines and protein synthetic capacity as a key function of its oncogenic output, and how this dependency may be perturbed through direct pharmacologic targeting of components of the protein synthetic machinery, such as the polyamines themselves, the eukaryotic translation initiation factor 4F (eIF4F) complex, and the eukaryotic translation initiation factor 5A (eIF5A). View Full-Text
Keywords: polyamines; MYC; protein synthesis in cancer; neuroblastoma polyamines; MYC; protein synthesis in cancer; neuroblastoma

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Flynn, A.T.; Hogarty, M.D. Myc, Oncogenic Protein Translation, and the Role of Polyamines. Med. Sci. 2018, 6, 41.

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