The role of TRAF1 in stabilizing TRAF2 from proteasome mediated degradation downstream of 4-1BB signaling (138.1)

Abstract TNF receptor family members play important roles in the innate and adaptive immune response, inducing signals for cell survival or apoptosis. This signaling in most cases relies on TNF receptor associated factors (TRAFs) to relay the signal from the TNFR family member to activation of NF-κB or MAPK pathways. Results from our lab have shown that TRAF1 is critical in the downregulation of the proapoptotic molecule Bim and the survival of activated and memory CD8 T cells, acting downstream of the prosurvival TNF receptor family member 4-1BB. We show here that in the absence of TRAF1, signaling downstream of 4-1BB results in the rapid proteasome dependent degradation of TRAF2. To identify interacting binding partners of TRAF1 that may mediate its stabilizing role on TRAF2 we performed a yeast two hybrid screen using a cDNA library from activated mouse lymph nodes. Among the interacting proteins identified were PSMC3, a subunit of the 19S regulatory particle of the 26S proteasome. We have confirmed the interaction between TRAF1 and PSMC3 in T cells and are currently investigating its functional role in the signaling downstream of 4-1BB. The results suggest that TRAF1 may have an important role in controlling the duration of the signal.