Ubiquitin ligase Smurf1 targets TRAF family proteins for ubiquitination and degradation.
The HECT-type E3 Smad ubiquitination regulation factor 1 (Smurf1) functions in regulation of cell polarity and bone homeostasis by targeting Smads, Runx2, RhoA and MEKK2 for ubiquitination and degradation. In a yeast two-hybrid screening, we identified TNF receptor-associated factor 4 (TRAF4) as a candidate substrate and was further validated. The PY motifs of TRAF4 mediated the interaction with the second WW domain of Smurf1. Overexpression of Smurf1 reduced the protein levels of TRAF4 dependent of its E3 activity and the proteasome. Further, we showed that all six members of TRAF family could be ubiquitinated by Smurf1. Consequently, Smurf1 interfered with the functions of TRAFs in NF-kappaB signaling under stimulation or not. These results suggested a new role of Smurf1 in inflammation and immunity through controlling the degradation of TRAFs.
Li
Shan
S
State Key Laboratory of Proteomics, Department of Genomics and Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.
Lu
Kefeng
K
Wang
Jian
J
An
Liguo
L
Yang
Guiwen
G
Chen
Hui
H
Cui
Yu
Y
Yin
Xiushan
X
Xie
Ping
P
Xing
Guichun
G
He
Fuchu
F
Zhang
Lingqiang
L
D020816:Amino Acid Motifs; D002460:Cell Line; D006801:Humans; D017434:Protein Structure, Tertiary; D053449:TNF Receptor-Associated Factor 4 / Q000235:genetics / Q000378:metabolism*; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
D053449:TNF Receptor-Associated Factor 4; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D025801:Ubiquitin; C498342:SMURF1 protein, human; D044767:Ubiquitin-Protein Ligases