PXD026329

PXD026329 is an original dataset announced via ProteomeXchange.

Title	YBX1 mediates translation of oncogenic transcripts to control cell competition in AML
Description	Persistence of malignant clones following cytotoxic or targeted therapy is a major determinant of adverse outcome in patients with hematologic malignancies. Despite the fact that the majority of patients with acute myeloid leukemia (AML) achieve complete remission after chemotherapy, a large proportion of them relapse as a result of residual malignant cells. After discontinuation of treatment, these persistent clones have a competitive advantage and re-establish disease. Therefore, targeting strategies that specifically reduce competitive advantage of malignant cells while leaving normal cells unaffected are clearly warranted. Recently, our group identified cold-shock protein and splicing factor YBX1 as a mediator of disease persistence in JAK2-mutated myeloproliferative neoplasia. The role of cold-shock proteins in AML, however, remained so far elusive. Using genetic screening, we identified YBX1 as a relevant functional dependency in AML. Inactivation of YBX1 in vitro and in vivo confirmed its role as an essential driver of leukemia development and maintenance. Here, we identified its ability to bind specific mRNAs, including MYC, and amplify their translation at the ribosomes by recruitment to polysomal chains. Genetic inactivation of YBX1 disrupted this regulatory circuit and displaced a number of oncogenic drivers from polysomes, with subsequent depletion of protein abundance. As a consequence, leukemia cells showed reduced proliferation and were out-competed in vitro and in vivo, while normal cells remained largely unaffected. Collectively, this data establishes YBX1 as a specific dependency and therapeutic target in AML that is essentially required for oncogenic protein expression.
HostingRepository	PRIDE
AnnounceDate	2021-11-03
AnnouncementXML	Submission_2021-11-03_05:56:41.128.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ashokkumar Jayavelu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-05-27 22:56:47	ID requested
⏵ 1	2021-11-03 05:56:41	announced

Perner F, Schnoeder TM, Xiong Y, Jayavelu AK, Mashamba N, Santamaria NT, Huber N, Todorova K, Hatton C, Perner B, Eifert T, Murphy C, Hartmann M, Hoell JI, Schr, ö, der N, Brandt S, Hochhaus A, Mertens PR, Mann M, Armstrong SA, Mandinova A, Heidel FH, YBX1 mediates translation of oncogenic transcripts to control cell competition in AML. Leukemia, 36(2):426-437(2022) [pubmed]

submitter keyword: YBX1, AML, Proteome, Oncogene, Translation

Prof.Dr.Matthias Mann
contact affiliation	Department of Proteomics and Signal Transduction. MaxPlanck Institute of Biochemistry
contact email	mmann@biochem.mpg.de
lab head
Ashokkumar Jayavelu
contact affiliation	Dept Proteomics and Signal Transduction, MaxPlanck Institute of Biochemistry
contact email	jayavelu@biochem.mpg.de
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/2021/11/PXD026329

PRIDE project URI

• PRIDE
  1. PXD026329
     1. Label: PRIDE project
     2. Name: YBX1 mediates translation of oncogenic transcripts to control cell competition in AML