Regulation of Smad Degradation and Activity by Smurf2, an E3 Ubiquitin Ligase

Smad proteins are key intracellular signaling effectors for the transforming growth factor-β superfamily of peptide growth factors. Following receptor-induced activation, Smads move into the nucleus to activate transcription of a select set of target genes. The activity of Smad proteins must be tigh...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2001-01, Vol.98 (3), p.974-979
Main Authors: Zhang, Ying, Chang, Chenbei, Gehling, Daniel J., Hemmati-Brivanlou, Ali, Derynck, Rik
Format: Article
Language:English
Subjects:
Acetylcysteine - analogs & derivatives
Acetylcysteine - pharmacology
Amino Acid Sequence
Amino acids
Animals
Binding Sites
Biological Sciences
Cellular biology
Cloning, Molecular
Complementary DNA
COS cells
Cysteine Proteinase Inhibitors - pharmacology
Databases as Topic
DNA-Binding Proteins - metabolism
Embryos
Enzymes
Gene expression regulation
Humans
Ligases - chemistry
Ligases - genetics
Ligases - metabolism
Mesoderm
Molecular Sequence Data
Oocytes - physiology
Peptides
Plasmids
Proteins
Receptors
Recombinant Proteins - chemistry
Recombinant Proteins - metabolism
Sequence Alignment
Sequence Homology, Amino Acid
Smad Proteins
Smad1 Protein
Smad2 Protein
Substrate Specificity
Trans-Activators - metabolism
Ubiquitin-Protein Ligases
Ubiquitins
Xenopus
Xenopus laevis
Xenopus Proteins
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Summary:Smad proteins are key intracellular signaling effectors for the transforming growth factor-β superfamily of peptide growth factors. Following receptor-induced activation, Smads move into the nucleus to activate transcription of a select set of target genes. The activity of Smad proteins must be tightly regulated to exert the biological effects of different ligands in a timely manner. Here, we report the identification of Smurf2, a new member of the Hect family of E3 ubiquitin ligases. Smurf2 selectively interacts with receptor-regulated Smads and preferentially targets Smad1 for ubiquitination and proteasome-mediated degradation. At higher expression levels, Smurf2 also decreases the protein levels of Smad2, but not Smad3. In Xenopus embryos, ectopic Smurf2 expression specifically inhibits Smad1 responses and thereby affects embryonic patterning by bone morphogenetic protein signals. These findings suggest that Smurf2 may regulate the competence of a cell to respond to transforming growth factor-β/bone morphogenetic protein signaling through a distinct degradation pathway that is similar to, yet independent of, Smurf1.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.98.3.974