P-stalk ribosomes act as master regulators of cytokine-mediated processes

Anna Dopler, Ferhat Alkan, Yuval Malka, Rob van der Kammen, Kelly Hoefakker, Daniel Taranto, Naz Kocabay, Iris Mimpen, Christel Ramirez, Elke Malzer, Olga I Isaeva, Mandy Kerkhoff, Anastasia Gangaev, Joana Silva, Sofia Ramalho, Liesbeth Hoekman, Maarten Altelaar, Roderick Beijersbergen, Leila Akkari, Jonathan Wilson YewdellPia Kvistborg, William James Faller*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Inflammatory cytokines are pivotal to immune responses. Upon cytokine exposure, cells enter an "alert state" that enhances their visibility to the immune system. Here, we identified an alert-state subpopulation of ribosomes defined by the presence of the P-stalk. We show that P-stalk ribosomes (PSRs) are formed in response to cytokines linked to tumor immunity, and this is at least partially mediated by P-stalk phosphorylation. PSRs are involved in the preferential translation of mRNAs vital for the cytokine response via the more efficient translation of transmembrane domains of receptor molecules involved in cytokine-mediated processes. Importantly, loss of the PSR inhibits CD8+ T cell recognition and killing, and inhibitory cytokines like transforming growth factor β (TGF-β) hinder PSR formation, suggesting that the PSR is a central regulatory hub upon which multiple signals converge. Thus, the PSR is an essential mediator of the cellular rewiring that occurs following cytokine exposure via the translational regulation of this process.

Original languageEnglish
Pages (from-to)6981-6993.e23
JournalCell
Volume187
Issue number24
DOIs
Publication statusPublished - 27 Nov 2024

Bibliographical note

Publisher Copyright:
© 2024 The Author(s)

Funding

A.D. and S.R. are supported by the NWO ( OCENW-M20-373 ). A.D. is supported by the Mark Foundation ( 21-053-ASP ). F.A., J.S., and Y.M. are supported by the KWF ( 13878 ). R.B. and E.M. are supported by the KWF ( 12539 ).

FundersFunder number
Nederlandse Organisatie voor Wetenschappelijk OnderzoekOCENW-M20-373
Mark Foundation21-053-ASP
KWF Kankerbestrijding12539, 13878

    Keywords

    • P-stalk
    • T cells
    • cytokines
    • melanoma
    • ribosome

    Fingerprint

    Dive into the research topics of 'P-stalk ribosomes act as master regulators of cytokine-mediated processes'. Together they form a unique fingerprint.

    Cite this