| 1. |
- Grönroos, Eva, et al.
(författare)
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Control of Smad7 stability by competition between acetylation and ubiquitination
- 2002
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Ingår i: Molecular Cell. - 1097-2765 .- 1097-4164. ; 10:3, s. 483-493
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Tidskriftsartikel (refereegranskat)abstract
- Smad proteins regulate gene expression in response to TGFbeta signaling. Here we present evidence that Smad7 interacts with the transcriptional coactivator p300, resulting in acetylation of Smad7 on two lysine residues in its N terminus. Acetylation or mutation of these lysine residues stabilizes Smad7 and protects it from TGFbeta-induced degradation. Furthermore, we demonstrate that the acetylated residues in Smad7 also are targeted by ubiquitination and that acetylation of these lysine residues prevents subsequent ubiquitination. Specifically, acetylation of Smad7 protects it against ubiquitination and degradation mediated by the ubiquitin ligase Smurf1. Thus, our data suggest that competition between ubiquitination and acetylation of overlapping lysine residues constitutes a novel mechanism to regulate protein stability.
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| 2. |
- Lönn, Peter, et al.
(författare)
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PARP-1 attenuates Smad-mediated transcription
- 2010
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Ingår i: Molecular Cell. - : Elsevier BV. - 1097-2765 .- 1097-4164. ; 40:4, s. 521-532
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Tidskriftsartikel (refereegranskat)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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