Smurf2 is a TRAF2 binding protein that triggers TNF-R2 ubiquitination and TNF-R2-induced JNK activation |
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Authors: | Carpentier Isabelle Coornaert Beatrice Beyaert Rudi |
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Institution: | a Department of Molecular Biology, Ghent University, Technologiepark 927, B-9052 Gent, Belgium b Department for Molecular Biomedical Research, Unit of Molecular Signal Transduction in Inflammation, VIB, Technologiepark 927, B-9052 Gent, Belgium |
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Abstract: | TRAF2 plays a central role in TNF-induced signalling to NF-κB 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-κB activation remained unaffected. These results suggest an important role for Smurf2 binding to TRAF2 in determining specific signalling outputs of TNF-R2. |
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Keywords: | Smurf2 TRAF2 TNF-R2 JNK Ubiquitination |
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