PXD056415-1

PXD056415 is an original dataset announced via ProteomeXchange.

Title	mTOR signaling promotes cytokine production in T cells through 3’UTR-mediated translation control
Description	T cells are key contributors to clear our body from infected and malignant cells. When T cells respond to target cells, they undergo profound translational alterations. The evolutionary and highly conserved kinase mammalian target of rapamycin (mTOR) is a central mediator of T cell differentiation, homeostasis, and T cell activation, including the production of the key pro-inflammatory cytokines TNF, IL2, and IFNγ. mTOR was shown to execute its translation activity through TOP motifs located in the 5’ Untranslated region (5’UTR) of its target genes. Here, we uncovered a distinct mechanism of mTOR signaling on cytokine production in T cells, which is under control of the 3’UTR. Even though non-classical TOP motifs are present in cytokine 3’UTRs, they do not contribute to mTOR-mediated translation regulation. Rather, AU-rich elements (AREs) are required for mTOR-mediated cytokine production. Furthermore, we discovered that the RNA binding protein DDX21 binds to 3’UTR AREs and confers the mTOR-mediated translation control. In conclusion, we here present a previously unappreciated ARE-dependent, 3’UTR-mediated mode of action that mTOR employs to regulate cytokine production.
HostingRepository	PRIDE
AnnounceDate	2025-11-17
AnnouncementXML	Submission_2025-11-17_02:49:38.036.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Floris van Alphen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-01 01:18:22	ID requested
⏵ 1	2025-11-17 02:49:38	announced

10.1016/J.MOLCEL.2025.11.005;

submitter keyword: mTor signaling, AU-rich elements, 3' untranslated region, Cytokines,T cells, post-transcriptional regulation

Monika C. Wolkers, PhD
contact affiliation	Sanquin Blood Supply Foundation, Department of Research, T cell differentiation lab, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands, and Oncode Institute, Utrecht, The Netherlands
contact email	M.wolkers@sanquin.nl
lab head
Floris van Alphen
contact affiliation	Sanquin Research
contact email	f.vanalphen@sanquin.nl
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/2025/11/PXD056415

PRIDE project URI

• PRIDE
  1. PXD056415
     1. Label: PRIDE project
     2. Name: mTOR signaling promotes cytokine production in T cells through 3’UTR-mediated translation control