PARP-1 attenuates Smad-mediated transcription Lönn, P. et al. Mol. Cell 40, 521–532 (2010)
Transforming growth factor-β (TGFβ) activates receptors to phosphorylate SMAD2 and SMAD3, enabling them to form a complex with SMAD4. This complex coordinates SMAD-activated transcription until transcription is terminated by the dephosphorylation, nuclear export or degradation of SMADs. Lönn et al. now show that poly(ADP-ribose) polymerase 1 (PARP1) — which covalently attaches ADP-ribose to substrates during poly(ADP-ribosyl)ation (PARylation) — can also terminate SMAD-activated transcription. PARP1 interacts with SMAD2, SMAD3 and SMAD4 in the nucleus, in response to TGFβ, and induces the PARylation of SMAD3 and SMAD4 in vitro and in vivo. This reduces the amount of SMAD3–SMAD4 bound to DNA, and attenuates the effects of SMADs on transcription. Depletion of PARP1 enhances the TGFβ-induced transdifferentiation of epithelial cells to mesenchymal cells, suggesting that PARylation can regulate SMADs in physiological settings. Thus, SMAD PARylation can also terminate SMAD-mediated transcription.
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