Conserved phosphorylation events in ESRRB integrate diverse signaling pathways to govern the fate of embryonic stem cells
Year: 2026
Type: article
Abstract: Embryonic stem cells are self-renewing, pluripotent cells, normally maintained by several pluripotency transcription factors. To respond to diverse differentiation and stress signaling pathways, the undifferentiated cell state must be destabilized before embryonic stem cells can properly interpret external signals to decide the cell fate. It remains incompletely understood how diverse signals promote the exit of the self-renewal state. Here, we show that both acute DNA damage and diverse differentiation signaling pathways converge at the proteasomal destruction of Estrogen-related receptor β (ESRRB), a key pluripotency transcription factor. Environmental agents such as UV light and genotoxic chemicals activate P-TEFb protein kinase to directly phosphorylate ESRRB to promote its proteasomal degradation. On the other hand, diverse differentiation signaling pathways also promote ESRRB degradation. Interestingly, the responsible kinase is GSK3β, instead of P-TEFb, in these biological contexts. Substituting five Ser residues in ESRRB with Ala confers resistance to GSK3β-dependent ESRRB degradation and compromises cell differentiation. These results demonstrate that conserved post-translational modifications in ESRRB integrate diverse signaling pathways to govern the fate of embryonic stem cells.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7221466813