Regulation of TGF-β signal transduction by mono- and deubiquitylation of Smads

Polyubiquitylation leading to proteasomal degradation is a well-established mechanism for regulat- ing TGF-b signal transduction components such as receptors and Smads. Recently, an equally impor- tant role was suggested for monoubiquitylation of both Smad4 and receptor-associated Smads that regulates their function without protein degradation. Monoubiquitylation of Smads was discovered following the identification of deubiquitylases required for TGF-b signaling, suggesting that contin- uous cycles of Smad mono- and deubiquitylation are required for proper TGF-b signal transduction. Here we summarize and discuss recent work on Smad mono- and deubiquitylation.