PXD051459

PXD051459 is an original dataset announced via ProteomeXchange.

Title	The TP53-activated E3 ligase RNF144B is a tumour suppressor that prevents genomic instability
Description	Background: TP53, the most frequently mutated gene in human cancers, orchestrates a complex transcriptional program crucial for cancer prevention. While certain TP53-dependent genes have been extensively studied, others, like the recently identified RNF144B, remained poorly understood. This E3 ubiquitin ligase has shown potent tumor suppressor activity in murine Eμ Myc-driven lymphoma, emphasizing its significance in the TP53 network. However, little is known about its targets and its role in cancer development, requiring further exploration. In this work, we investigate RNF144B's impact on tumor suppression beyond the hematopoietic compartment in human cancers. Methods: Employing TP53 wild-type cells, we generated models lacking RNF144B in both non-transformed and cancerous cells of human and mouse origin. By using proteomics, transcriptomics, and functional analysis, we assessed RNF144B's impact in cellular proliferation and transformation. Through In vitro and in vivo experiments, we explored proliferation, transformation potential, DNA repair, cell cycle control, mitotic progression, and treatment resistance. Findings were contrasted with clinical datasets and bioinformatics analysis. Results: Our research underscores RNF144B's pivotal role as a tumor suppressor, particularly in lung adenocarcinoma. In both human and mouse oncogene-expressing cells, RNF144B deficiency heightened cellular proliferation and transformation. Proteomic and transcriptomic analysis revealed RNF144B's novel function in mediating protein degradation associated with cell cycle progression, DNA damage response and genomic stability. RNF144B deficiency induced chromosomal instability, mitotic defects, and correlated with elevated aneuploidy and worse prognosis in human tumors. Furthermore, RNF144B-deficient lung adenocarcinoma cells exhibited resistance to cell cycle inhibitors that induce chromosomal instability. Conclusions: PRJNA1092607Supported by clinical data, our study suggests that RNF144B plays a pivotal role in maintaining genomic stability during tumor suppression.
HostingRepository	PRIDE
AnnounceDate	2024-06-23
AnnouncementXML	Submission_2024-06-23_01:38:00.302.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gerard Romero
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-15 13:57:56	ID requested
⏵ 1	2024-06-23 01:38:01	announced

10.1186/s13046-024-03045-4;

Abad E, Sandoz J, Romero G, Zadra I, Urgel-Solas J, Borredat P, Kourtis S, Ortet L, Mart, í, nez CM, Weghorn D, Sdelci S, Janic A, The TP53-activated E3 ligase RNF144B is a tumour suppressor that prevents genomic instability. J Exp Clin Cancer Res, 43(1):127(2024) [pubmed]

submitter keyword: tumor suppressor, genomic instability,cancer, aneuploidy

Ana Janic
contact affiliation	Department of Medicine and Life Sciences, Pompeu Fabra University, 08003, Barcelona, Spain.
contact email	ana.janic@upf.edu
lab head
Gerard Romero
contact affiliation	Vall d'Hebrón Institute of Oncology (VHIO)
contact email	grspianus1999@gmail.com
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/2024/06/PXD051459

PRIDE project URI

• PRIDE
  1. PXD051459
     1. Label: PRIDE project
     2. Name: The TP53-activated E3 ligase RNF144B is a tumour suppressor that prevents genomic instability