PXD064727-1

PXD064727 is an original dataset announced via ProteomeXchange.

Title	Ribosomal protein L5 (RPL5/uL18) I60V mutation is associated to increased translation and modulates drug sensitivity in T-cell acute lymphoblastic leukemia cells
Description	Somatic mutations in ribosomal proteins (RPs), including RPL5, have been reported in approximately 10% of pediatric patients with T-cell acute lymphoblastic leukemia (T-ALL). In cancer, the incorporation of mutant RPs into ribosomes often disrupts canonical ribosome function, thereby contributing to disease development. In this study, we aimed to characterize the effects of the RPL5-I60V mutation in the context of T-ALL, focusing on its impact on translation and cellular responses to a panel of compounds in vitro. Using CRISPR-Cas9, we generated a homozygous knock-in mutant in Jurkat cells and investigated its effects on ribosome biogenesis. We observed both quantitative and qualitative alterations in the production of the large ribosomal subunit. Ribosomes containing the mutant RPL5 protein exhibited intrinsically increased protein synthesis activity, which correlated with enhanced cellular proliferation. We then evaluated the response of these mutant cells to a panel of compounds targeting protein synthesis at various levels—including an MNK1 inhibitor, metformin, silvestrol, homoharringtonine, anisomycin, resveratrol, and hygromycin B—as well as cytarabine, a chemotherapeutic agent commonly used in T-ALL treatment. Our results showed that the RPL5-I60V mutation confers increased sensitivity to most of these compounds, with the exception of hygromycin B. This study advances our understanding of how oncoribosomes contribute to cancer pathogenesis and highlights the therapeutic potential of directly or indirectly targeting altered ribosomes, offering insights for the development of personalized treatment strategies.
HostingRepository	PRIDE
AnnounceDate	2025-11-06
AnnouncementXML	Submission_2025-11-06_03:16:52.445.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD064727
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Hesse Anne-Marie
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-06 08:10:26	ID requested
⏵ 1	2025-11-06 03:16:53	announced

Bacci L, Pollutri D, Ripa IJ, D'Andrea M, Marchand V, Motorin Y, Hesse AM, Cout, é Y, Filipek K, Penzo M, Ribosomal protein L5 (RPL5/uL18) I60V mutation is associated to increased translation and modulates drug sensitivity in T-cell acute lymphoblastic leukemia cells. Biochem Pharmacol, 243(Pt 1):117497(2026) [pubmed]

10.1016/j.bcp.2025.117497;

10.6019/PXD064727;

submitter keyword: ribosomes, target therapy,Cancer, LC-MS/MS

Yohann Couté
contact affiliation	Univ. Grenoble Alpes, INSERM, CEA, UA13 BGE, CNRS, CEA, FR2048, F-38000 Grenoble, France.
contact email	yohann.coute@cea.fr
lab head
Hesse Anne-Marie
contact affiliation	Laboratoire d'Etude de la Dynamique des Protéomes
contact email	anne-marie.hesse@cea.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD064727
     1. Label: PRIDE project
     2. Name: Ribosomal protein L5 (RPL5/uL18) I60V mutation is associated to increased translation and modulates drug sensitivity in T-cell acute lymphoblastic leukemia cells