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PXD045451

PXD045451 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe GC-rich element withing the 5'UTR of β-catenin mRNa modulates its translation under hypoxia
DescriptionProtein 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.
HostingRepositoryPRIDE
AnnounceDate2025-05-06
AnnouncementXMLSubmission_2025-05-06_11:44:11.597.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD045451
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterJohana Chicher
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-09-18 04:47:48ID requested
12025-05-06 11:44:12announced
Publication List
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]
Keyword List
submitter keyword: Translation, hypoxia, beta-catenin
Contact List
Angelita Simonetti
contact affiliationCNRS UPR9002 (ARN), Institut de Biologie Moléculaire et Cellulaire, Université de Strasbourg, Strasbourg 67000, France.
contact emaila.simonetti@ibmc-cnrs.unistra.fr
lab head
Johana Chicher
contact affiliationUniversité de Strasbourg, Plateforme Protéomique Strasbourg-Esplanade, Centre National de la Recherche Scientifique
contact emailj.chicher@ibmc-cnrs.unistra.fr
dataset submitter
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