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PMID:19937093

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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

Significance

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


See also

References

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