Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation.
Smad7 is an inhibitory Smad that acts as a negative regulator of signaling by the transforming growth factor-beta (TGF-beta) superfamily proteins. Smad7 is induced by TGF-beta, stably interacts with activated TGF-beta type I receptor (TbetaR-I), and interferes with the phosphorylation of receptor-regulated Smads. Here we show that Smurf1, an E3 ubiquitin ligase for bone morphogenetic protein-specific Smads, also interacts with Smad7 and induces Smad7 ubiquitination and translocation into the cytoplasm. In addition, Smurf1 associates with TbetaR-I via Smad7, with subsequent enhancement of turnover of TbetaR-I and Smad7. These results thus reveal a novel function of Smad7, i.e. induction of degradation of TbetaR-I through recruitment of an E3 ligase to the receptor.
Ebisawa
T
T
Department of Biochemistry, The Cancer Institute of the Japanese Foundation for Cancer Research, and Research for the Future Program, the Japan Society for the Promotion of Science, 1-37-1 Kami-ikebukuro, Toshima-ku, Tokyo 170-8455, Japan.
Fukuchi
M
M
Murakami
G
G
Chiba
T
T
Tanaka
K
K
Imamura
T
T
Miyazono
K
K
D030201:Activin Receptors, Type I; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D008025:Ligases / Q000378:metabolism*; D008907:Mink; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology*; D051905:Smad6 Protein; D051906:Smad7 Protein; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases
D004268:DNA-Binding Proteins; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; C497802:SMAD6 protein, human; C497806:SMAD7 protein, human; D051905:Smad6 Protein; D051906:Smad7 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; C471641:SMURF2 protein, human; D044767:Ubiquitin-Protein Ligases; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D008025:Ligases