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. Author manuscript; available in PMC: 2013 Jul 4.
Published in final edited form as: FEBS Lett. 2012 Mar 24;586(14):1913–1920. doi: 10.1016/j.febslet.2012.03.037

Fig. 1. Smad4 regulation by mono- and deubiquitylation.

Fig. 1

A) Opposing roles of Ecto/Tif1-γ (an E3 ligase adds a monoubiquitin that destabilizes Smad4-R-Smad complexes - blue arrow) and FAM/Usp9x (a deubiquitylase that removes monoubiquitin and allows Smad4-R-Smad complex formation - green arrow) in TGF-β signaling. B-D) Model for activation of Smad4 monoubiquitylation by association with DNA. B) Ecto/Tif1-γ bound to an activated R-Smad-Smad4 complex is recruited to Smad-binding elements (SBE) in promoter DNA. C) The presence of specific histone marks such as acetylation (AC), possibly induced by transcriptionally-active Smads (green arrow), then activates Ecto ubiquitin ligase activity. D) Ecto/Tif1-γ then monoubiquitylates Smad4 (red arrow) causing the dissociation of the Smad complex and the cessation of transcription.

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