Publikation
Nuclear and cytosolic fractions of SOX2 synergize as transcriptional and translational co-regulators of cell fate.
Wissenschaftlicher Artikel/Review - 03.10.2024
Schaefer Thorsten, Mittal Nitish, Wang Hui, Ataman Meric, Candido Silvia, Lötscher Jonas, Velychko Sergiy, Tintignac Lionel, Bock Thomas, Börsch Anastasiya, Baßler Jochen, Rao Tata Nageswara, Zmajkovic Jakub, Roffeis Sarah, Loeliger Jordan, Jacob Francis, Dumlin Alain, Schürch Christoph, Schmidt Alexander, Skoda Radek C, Wymann Matthias P, Hess Christoph, Schöler Hans R, Zaehres Holm, Hurt Ed, Zavolan Mihaela, Lengerke Claudia
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Stemness 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.