PXD010924-2

PXD010924 is an original dataset announced via ProteomeXchange.

Title	Altered patterns of global protein synthesis and translational fidelity in RPS15-mutated chronic lymphocytic leukemia
Description	Genomic studies have recently identified RPS15 as a new driver gene in aggressive and chemorefractory cases of chronic lymphocytic leukemia (CLL). RPS15 encodes a ribosomal protein whose conserved C-terminal domain extends into the decoding center of the ribosome. We demonstrate that mutations in highly conserved residues of this domain affect both protein stability —by increasing its ubiquitin-mediated degradation— and cell proliferation rates. On the other hand, we show that mutated RPS15 can be loaded into the ribosomes, directly impacting on global protein synthesis and/or translational fidelity in a mutation-specific manner. Quantitative mass-spectrometry analyses suggest that RPS15 variants may induce additional alterations in the translational machinery as well as a metabolic shift at the proteome level in both HEK293T and MEC-1 cells. These results indicate that CLL-related RPS15 mutations might act following patterns known for other ribosomal diseases, likely switching from a hypo- to a hyperproliferative phenotype driven by mutated ribosomes. In this scenario, loss of translational fidelity causing altered cell proteostasis can be proposed as a new molecular mechanism involved in CLL pathobiology.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:06:25.410.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Miguel Prado
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2018-08-29 04:17:55	ID requested
1	2019-09-09 03:49:13	announced
⏵ 2	2024-10-22 04:06:26	announced	2024-10-22: Updated project metadata.

Bretones G, Á, lvarez MG, Arango JR, Rodr, í, guez D, Nadeu F, Prado MA, Vald, é, s-Mas R, Puente DA, Paulo JA, Delgado J, Villamor N, L, ó, pez-Guillermo A, Finley DJ, Gygi SP, Campo E, Quesada V, L, ó, pez-Ot, í, n C, Altered patterns of global protein synthesis and translational fidelity in RPS15-mutated chronic lymphocytic leukemia. Blood, 132(22):2375-2388(2018) [pubmed]

10.1182/blood-2017-09-804401;

curator keyword: Biomedical

submitter keyword: Chronic lymphocytic leukemia, translational fidelity, ribosomal decoding center, CLL, RPS15, proteostasis

Daniel J Finley
contact affiliation	Finley and Gygi lab - Cell Biology Department - Harvard Medical School
contact email	daniel_finley@hms.harvard.edu
lab head
Miguel Prado
contact affiliation	Harvard Medical School
contact email	miguel_prado@hms.harvard.edu
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/2019/09/PXD010924

PRIDE project URI

• PRIDE
  1. PXD010924
     1. Label: PRIDE project
     2. Name: Altered patterns of global protein synthesis and translational fidelity in RPS15-mutated chronic lymphocytic leukemia