PXD031361

PXD031361 is an original dataset announced via ProteomeXchange.

Title	The polyamine-hypusine circuit controls an oncogenic translational program necessary for MYC-driven lymphomagenesis
Description	MYC oncogenes are activated in broad spectrum of human malignancies and transcriptionally reprogram the genome to drive cancer cell growth. Given this it is unclear if targeting a single effector will have a therapeutic benefit. MYC activates the polyaminehypusine circuit, which post-translationally modifies the translation factor eIF5A. The hypusine axis has been proposed to suppress tumorigenesis. Here we report essential roles for hypusinated eIF5A in the development and maintenance of Myc-driven lymphoma, where loss of eIF5A hypusination abolishes malignant transformation. Mechanistically, integrating RNA-seq, Ribo-seq and proteomic analyses revealed that efficient translation of select targets is dependent upon eIF5A hypusination, including key regulators of G1 to S phase cell cycle progression. Notably, this circuit controls Myc’s proliferative response at several levels, and it is activated across multiple tumor types. These findings suggest the hypusine circuit as a therapeutic target for a broad spectrum of malignancies.
HostingRepository	PRIDE
AnnounceDate	2024-01-26
AnnouncementXML	Submission_2024-01-26_06:42:01.688.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD031361
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	John Koomen
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-31 02:04:55	ID requested
⏵ 1	2024-01-26 06:42:02	announced

Nakanishi S, Li J, Berglund AE, Kim Y, Zhang Y, Zhang L, Yang C, Song J, Mirmira RG, Cleveland JL, The Polyamine-Hypusine Circuit Controls an Oncogenic Translational Program Essential for Malignant Conversion in MYC-Driven Lymphoma. Blood Cancer Discov, 4(4):294-317(2023) [pubmed]

10.1158/2643-3230.bcd-22-0162;

10.6019/PXD031361;

submitter keyword: tumorigenesis, lymphoma, eIF5A, Dhps, MYC,Polyamine-hypusine, translation

John Cleveland
contact affiliation	Moffitt Cancer Center Tampa, FL, USA
contact email	john.cleveland@moffitt.org
lab head
John Koomen
contact affiliation	Moffitt Cancer Center
contact email	john.koomen@moffitt.org
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/01/PXD031361

PRIDE project URI

• PRIDE
  1. PXD031361
     1. Label: PRIDE project
     2. Name: The polyamine-hypusine circuit controls an oncogenic translational program necessary for MYC-driven lymphomagenesis