Figure 2
From: Non-degradative ubiquitination in Smad-dependent TGF-β signaling
![Figure 2](http://media.springernature.com/full/springer-static/image/art%3A10.1186%2F2045-3701-1-43/MediaObjects/13578_2011_Article_46_Fig2_HTML.jpg)
A model for mono-ubiquitination in TGF-β signaling. Upon TGF-β stimulation, Smad3 is phosphorylated at sites in both the linker and the C-terminal tail. Phosphorylation of T179 in the linker region potentiates Smurf2 binding and the subsequent mono-ubiquitination. Smad3 mono-ubiquitination can be reversed by USP15. On the other hand, mono-ubiquitination of Smad4 is induced by Ecto/Tif1γ, and reversed by FAM/USP9x. The unmodified Smad3 and Smad4 form a DNA binding complex that regulates target gene expression whereas mono-ubiquitinated Smad3 or Smad4 inhibits or disrupts the Smad complex formation.