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-β 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-β signaling, suggesting that continuous cycles of Smad mono- and deubiquitylation are required for proper TGF-β signal transduction. Here we summarize and discuss recent work on Smad mono- and deubiquitylation.
Department of Biomedical Sciences, University of Padova, Padova, Italy. dupont@bio.unipd.it
Sirio
S
Dupont
Masafumi
M
Inui
Stuart J
SJ
Newfeld
D000818:Animals; D010450:Endopeptidases / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008954:Models, Biological; D008957:Models, Genetic; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051901:Smad4 Protein / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D064570:Ubiquitin-Specific Proteases; D054875:Ubiquitination
C497796:SMAD4 protein, human; D051901:Smad4 Protein; C511956:TRIM33 protein, human; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C506234:USP9X protein, human; D025801:Ubiquitin; D010450:Endopeptidases; D043222:Ubiquitin Thiolesterase; D064570:Ubiquitin-Specific Proteases; D046988:Proteasome Endopeptidase Complex