PXD045451

PXD045451 is an original dataset announced via ProteomeXchange.

Title	The GC-rich element withing the 5'UTR of β-catenin mRNa modulates its translation under hypoxia
Description	Protein synthesis is a universal process mainly regulated at the initiation stage to permit a rapid and reversible control of cellular and environmental changes. Several stress conditions such as hypoxia, activate the translational reprogramming of mRNAs encoding proteins essential for stress recovery and cell survival. Increasing evidence of unconventional translation initiation mechanisms lead by 5’UTR motifs, shows the cells potential to adapt their translation machinery in response to different stimuli. β-catenin is an oncogenic protein playing an essential role in Wnt signal transduction. Dysregulation of this pathway causes aberrant nuclear β-catenin accumulation, which consequently modulates the expression of genes related to cancer development and metastasis. To date, the mechanism of its translation maintenance in stressed cells remains elusive. To understand how β-catenin mRNA escapes global translational blockade in hypoxic cancer cells, we determined the 5’UTR secondary structure and searched for translation regulatory elements in living cells. We found that a three-way junction (TWJ) within its 5’UTR is involved in the translation efficiency (TE) of β-catenin and its enhancement under hypoxia. We showed that the TWJ single-stranded polypurine region becomes, in the absence of eIF4E, an alternative anchoring site for eIF4B, eIF4A and eIF4G. Importantly, the TWJ makes the β-catenin mRNA translation eIF4A-dependent being sensible to silvestrol, a selective eIF4A inhibitor and promising anticancer agent. Our study unravels the 5’UTR-driven translation regulation mechanism of β-catenin mRNA and set the basis to explore its inhibition in the frame of cancer progression.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_11:44:11.597.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD045451
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Johana Chicher
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-18 04:47:48	ID requested
⏵ 1	2025-05-06 11:44:12	announced

10.6019/PXD045451;

10.1093/nar/gkaf321;

D'Agostino M, Rol-Moreno J, Bec G, Kuhn L, Ennifar E, Simonetti A, -catenin mRNA modulates its translation under hypoxia. Nucleic Acids Res, 53(8):(2025) [pubmed]

submitter keyword: Translation, hypoxia, beta-catenin

Angelita Simonetti
contact affiliation	CNRS UPR9002 (ARN), Institut de Biologie Moléculaire et Cellulaire, Université de Strasbourg, Strasbourg 67000, France.
contact email	a.simonetti@ibmc-cnrs.unistra.fr
lab head
Johana Chicher
contact affiliation	Université de Strasbourg, Plateforme Protéomique Strasbourg-Esplanade, Centre National de la Recherche Scientifique
contact email	j.chicher@ibmc-cnrs.unistra.fr
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/2025/05/PXD045451

PRIDE project URI

• PRIDE
  1. PXD045451
     1. Label: PRIDE project
     2. Name: The GC-rich element withing the 5'UTR of β-catenin mRNa modulates its translation under hypoxia