PMID:19937093

Citation	Li, S, Lu, K, Wang, J, An, L, Yang, G, Chen, H, Cui, Y, Yin, X, Xie, P, Xing, G, He, F and Zhang, L (2010) Ubiquitin ligase Smurf1 targets TRAF family proteins for ubiquitination and degradation. Mol. Cell. Biochem. 338:11-7
Abstract	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.
Links	PubMed Online version:10.1007/s11010-009-0315-y
Keywords	Amino Acid Motifs; Cell Line; Humans; Protein Structure, Tertiary; TNF Receptor-Associated Factor 4/genetics; TNF Receptor-Associated Factor 4/metabolism; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/genetics; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/metabolism; Two-Hybrid System Techniques; Ubiquitin/metabolism; Ubiquitin-Protein Ligases/genetics; Ubiquitin-Protein Ligases/metabolism; Ubiquitination
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:TRAF4	enables	GO:0050699: WW domain binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:Q9HCE7	F		Seeded From UniProt	complete
HUMAN:TRAF4	enables	GO:0005515: protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:Q9HCE7-2	F		Seeded From UniProt	complete
HUMAN:SMUF1	enables	GO:0005515: protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:Q9BUZ4	F		Seeded From UniProt	complete
HUMAN:RHOB	enables	GO:0005515: protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:Q9BUZ4	F		Seeded From UniProt	complete
HUMAN:SMUF1	involved_in	GO:0000209: protein polyubiquitination	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:SMUF1	enables	GO:0004842: ubiquitin-protein transferase activity	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
HUMAN:SMUF1	involved_in	GO:0006511: ubiquitin-dependent protein catabolic process	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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