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Suppression of TGF-β/SMAD signaling by an inner nuclear membrane phosphatase complex

Cytokines of the TGF-β superfamily control essential cell fate decisions via receptor regulated SMAD (R-SMAD) transcription factors. Ligand-induced R-SMAD phosphorylation in the cytosol triggers their activation and nuclear accumulation. We determine how R-SMADs are inactivated by dephosphorylation in the cell nucleus to counteract signaling by TGF-β superfamily ligands. 

Citation:
Ji Z, Siu WYS, Dueñas ME, Müller L, Trost M, Carvalho P. Suppression of TGF-β/SMAD signaling by an inner nuclear membrane phosphatase complex. Nat Commun. 2025;16(1).

Keywords:
Cell nucleus; metabolism; KEK293 cells; nuclear envelope; enzymology; phosphorylation; protein binding; signal transduction

Abstract:
Cytokines of the TGF-β superfamily control essential cell fate decisions via receptor regulated SMAD (R-SMAD) transcription factors. Ligand-induced R-SMAD phosphorylation in the cytosol triggers their activation and nuclear accumulation. We determine how R-SMADs are inactivated by dephosphorylation in the cell nucleus to counteract signaling by TGF-β superfamily ligands.