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. 2010 Nov 24;40(4):521-32.
doi: 10.1016/j.molcel.2010.10.029.

PARP-1 attenuates Smad-mediated transcription

Peter Lönn  1 , Lars P van der Heide, Markus Dahl, Ulf Hellman, Carl-Henrik Heldin, Aristidis Moustakas
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Free article

PARP-1 attenuates Smad-mediated transcription

Peter Lönn et al. Mol Cell. .
Free article

Abstract

The versatile cytokine transforming growth factor β (TGF-β) regulates cellular growth, differentiation, and migration during embryonic development and adult tissue homeostasis. Activation of TGF-β receptors leads to phosphorylation of Smad2 and Smad3, which oligomerize with Smad4 and accumulate in the nucleus where they recognize gene regulatory regions and orchestrate transcription. Termination of Smad-activated transcription involves Smad dephosphorylation, nuclear export, or ubiquitin-mediated degradation. In an unbiased proteomic screen, we identified poly(ADP-ribose) polymerase-1 (PARP-1) as a Smad-interacting partner. PARP-1 dissociates Smad complexes from DNA by ADP-ribosylating Smad3 and Smad4, which attenuates Smad-specific gene responses and TGF-β-induced epithelial-mesenchymal transition. Thus, our results identify ADP-ribosylation of Smad proteins by PARP-1 as a key step in controlling the strength and duration of Smad-mediated transcription.

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