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

Polyubiquitylation leading to proteasomal degradation is a well-established mechanism for regulating TGF-beta signal transduction components such as receptors and Smads. Recently, an equally important 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-beta signaling, suggesting that continuous cycles of Smad mono- and deubiquitylation are required for proper TGF-beta signal transduction. Here we summarize and discuss recent work on Smad mono- and deubiquitylation. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.