Smurf2 is a TRAF2 binding protein that triggers TNF-R2 ubiquitination and TNF-R2-induced JNK activation
- Resource Type
- Authors
- Isabelle Carpentier; Rudi Beyaert; Beatrice Coornaert
- Source
- Biochemical and Biophysical Research Communications. 374:752-757
- Subject
- TRAF2
Ubiquitin-Protein Ligases
p38 mitogen-activated protein kinases
Binding protein
JNK Mitogen-Activated Protein Kinases
Ubiquitination
Biophysics
Cell Biology
Biology
Ubiquitin-conjugating enzyme
TNF Receptor-Associated Factor 2
Biochemistry
Molecular biology
Cell Line
Ubiquitin ligase
Cell biology
Enzyme Activation
Enzyme activator
Ubiquitin
Two-Hybrid System Techniques
biology.protein
Humans
Receptors, Tumor Necrosis Factor, Type II
Receptor
Molecular Biology
- Language
- ISSN
- 0006-291X
TRAF2 plays a central role in TNF-induced signalling to NF-kappaB and JNK/p38 MAPK. To better understand the molecular mechanisms that mediate this dual function of TRAF2, we performed a yeast two-hybrid screening for TRAF2 interacting proteins using the Sos recruitment system. This resulted in the identification of the E3 ubiquitin ligase Smurf2 as a TRAF2 binding protein. TRAF2 overexpression was shown to trigger Smurf2 ubiquitination and the formation of a TNF-R2/Smurf2 complex. Smurf2 on its turn promoted TNF-R2 ubiquitination and the relocalization of TNF-R2 as well as TRAF2 to a detergent-insoluble cell fraction. This was associated with enhanced TNF-R2-induced JNK activation, whereas TNF-R2-induced NF-kappaB activation remained unaffected. These results suggest an important role for Smurf2 binding to TRAF2 in determining specific signalling outputs of TNF-R2.