PARP-1 attenuates Smad-mediated transcription
2010 (English)In: Molecular Cell, ISSN 1097-2765, E-ISSN 1097-4164, Vol. 40, no 4, 521-532 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2010. Vol. 40, no 4, 521-532 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-128847DOI: 10.1016/j.molcel.2010.10.029ISI: 000284988400006PubMedID: 21095583OAI: oai:DiVA.org:uu-128847DiVA: diva2:331941