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Supplementary Tables S1, S2, S5-S13 from The Polyamine–Hypusine Circuit Controls an Oncogenic Translational Program Essential for Malignant Conversion in MYC-Driven Lymphoma

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posted on 2023-07-05, 08:41 authored by Shima Nakanishi, Jiannong Li, Anders E. Berglund, Youngchul Kim, Yonghong Zhang, Ling Zhang, Chunying Yang, Jinming Song, Raghavendra G. Mirmira, John L. Cleveland

Supplementary Tables S1, S2, S5-S13 includes Supplementary Tables S1, S2, S5-S13. Supplementary Table S1 provides a summary of BL and DHL patient demographics for the immunohistochemistry study presented in Fig. 1, E and F. Supplementary Table S2 lists the MYC-dysregulated genes whose expression is significantly altered following depletion of eIF5A or DHPS, related to Fig. 4F. Supplementary Table S5 shows DHPS GISTIC count and survival of select TCGA PanCancer datasets, related to Fig. 7J. Supplementary Table S6 shows the genetic mouse models used in this study, related to Methods. Supplementary Table S7 shows the mouse and human cell lines used in this study, related to Methods. Supplementary Table S8 lists the antibodies used in this study, related to Methods. Supplementary Table S9 lists reagents used in this study, related to Methods. Supplementary Table S10 summarizes the plasmids used in this study, related to Methods. Supplementary Table S11 lists the sequences of the oligonucleotides used in this study, related to Methods. Supplementary Table S12 lists accession numbers and publicly deposited data from this study, related to Methods. Supplementary Table S13 lists software and algorithms used in this study, related to Methods.

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National Cancer Institute (NCI)

United States Department of Health and Human Services

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ARTICLE ABSTRACT

The MYC oncoprotein is activated in a broad spectrum of human malignancies and transcriptionally reprograms the genome to drive cancer cell growth. Given this, it is unclear if targeting a single effector of MYC will have therapeutic benefit. MYC activates the polyamine–hypusine circuit, which posttranslationally modifies the eukaryotic translation factor eIF5A. The roles of this circuit in cancer are unclear. Here we report essential intrinsic roles for hypusinated eIF5A in the development and maintenance of MYC-driven lymphoma, where the loss of eIF5A hypusination abolishes malignant transformation of MYC-overexpressing B cells. Mechanistically, integrating RNA sequencing, ribosome sequencing, and proteomic analyses revealed that efficient translation of select targets is dependent upon eIF5A hypusination, including regulators of G1–S phase cell-cycle progression and DNA replication. This circuit thus controls MYC's proliferative response, and it is also activated across multiple malignancies. These findings suggest the hypusine circuit as a therapeutic target for several human tumor types. Elevated EIF5A and the polyamine–hypusine circuit are manifest in many malignancies, including MYC-driven tumors, and eIF5A hypusination is necessary for MYC proliferative signaling. Not­ably, this circuit controls an oncogenic translational program essential for the development and maintenance of MYC-driven lymphoma, supporting this axis as a target for cancer prevention and treatment.See related commentary by Wilson and Klein, p. 248.This article is highlighted in the In This Issue feature, p. 247

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