Functions of TRAF1 in tumor necrosis factor (TNF) receptor signaling

• Applicant: Professor Dr. Harald Günther Wajant
• Subject Area: Cell Biology
• Term: from 2006 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 27951417

TNF receptor associated factor (TRAF) proteins play a pivotal role in signaling cascades, triggered by receptors of the TNF receptor (TNFR) and Interleukin-1 receptor/Toll-like receptor (IL1R/TLR) families. Although there was considerable progress in the molecular understanding of TRAF2, 3 and 6, the biological functions of TRAF1 are poorly defined. It has been shown that TRAF1 regulates signaling properties of other TRAF proteins and thus functions of TNFRs and TLRs. We did previously find that TRAF1 does differentially affect NF¿B activation by various TNF receptors, ranging from strong activation to neutral or even inhibiting effects. In the proposed project, we would like to investigate in more detail the interplay of TRAF1 and TNFRs. We want to define the molecular mechanisms that enable TRAF1 to elicit its diverse regulatory effects on TNFR-mediated NF¿B activation. Moreover, we will verify a possible role of TRAF1 in regulation of mitogen-activated protein kinases and Akt activation by TNF receptors, as well as TLR receptors. Finally, we want to extend our knowledge on the functions of a TRAF1 cleavage product that acts as a global inhibitor of NF¿B signaling.

• DFG Programme: Research Grants