The recently identified TRAF family (TRAF 1-6) has been implicated in the signal transduction of many members of the TNF receptor superfamily, such as TNF receptors 1 and 2 (TNF-R1 and TNF-R2), lymphotoxin beta receptor (LTBR), CD40, CD30 and the Epstein Barr virus (EBV)-encoded oncogene latent membrane protein 1 (LMP-1), as well as in the signaling of the pro-inflammation cytokine interleukin-1 (IL-1). One of the most important down stream events of TRAF signaling is the activation of nuclear factor kappa B (NF-kB), a transcription factor that turns on numerous genes involved in inflammatory, immune and acute phase response. The main objectives are to determine the crystal structures of TRAFs in isolation and in complex with upstream receptors, and to understand the mechanism of TRAF oligomerization, the structural basis of receptor interactions and the mode of signal transduction by combining the structural information with biochemical and biophysical methods. TRAF-mediated signal transductions are, on the one hand, important aspects of the host defense system and, on the other hand, contributing factors to inflammation and tumorigenesis. Therefore, the proposed study should have therapeutic implications by providing the possibility for structure-based approaches.
Showing the most recent 10 out of 41 publications
