Schaefer, ThorstenThorstenSchaeferMittal, NitishNitishMittalWang, HuiHuiWangAtaman, MericMericAtamanCandido, SilviaSilviaCandidoLötscher, JonasJonasLötscherVelychko, SergiySergiyVelychkoTintignac, LionelLionelTintignacBock, ThomasThomasBockBörsch, AnastasiyaAnastasiyaBörschBaßler, JochenJochenBaßlerTata, Nageswara RaoNageswara RaoTataZmajkovic, JakubJakubZmajkovicRoffeis, SarahSarahRoffeisLöliger, JordanJordanLöligerJacob, FrancisFrancisJacobDumlin, AlainAlainDumlinSchürch, ChristophChristophSchürchSchmidt, AlexanderAlexanderSchmidtSkoda, Radek CRadek CSkodaWymann, Matthias PMatthias PWymannHess, ChristophChristophHessSchöler, Hans RHans RSchölerZaehres, HolmHolmZaehresHurt, EdEdHurtZavolan, MihaelaMihaelaZavolanLengerke, ClaudiaClaudiaLengerke2024-11-142024-11-142024-10-22https://boris-portal.unibe.ch/handle/20.500.12422/188951Stemness and pluripotency are mediated by transcriptional master regulators that promote self-renewal and repress cell differentiation, among which is the high-mobility group (HMG) box transcription factor SOX2. Dysregulated SOX2 expression, by contrast, leads to transcriptional aberrations relevant to oncogenic transformation, cancer progression, metastasis, therapy resistance, and relapse. Here, we report a post-transcriptional mechanism by which the cytosolic pool of SOX2 contributes to these events in an unsuspected manner. Specifically, a low-complexity region within SOX2's C-terminal segment connects to the ribosome to modulate the expression of cognate downstream factors. Independent of nuclear structures or DNA, this C-terminal functionality alone changes metabolic properties and induces non-adhesive growth when expressed in the cytosol of SOX2 knockout cells. We thus propose a revised model of SOX2 action where nuclear and cytosolic fractions cooperate to impose cell fate decisions via both transcriptional and translational mechanisms.enCP: Developmental biologyCP: Molecular biologySOX2cancerdifferentiationribosomestem celltranslation600 - Technology::610 - Medicine & healtharticle10.48620/762303936808310.1016/j.celrep.2024.114807