genesis of a class of proteins associated with bacterial pathogenesis, but also provide evidence for a novel signal peptide function. The second aim of the project is to elucidate the function of factors that facilitate the transport of proteins across or insertion into the ER or bacterial IM. In the last year we have continued to study the structure and membrane distribution of YidC, a highly conserved bacterial protein that has been shown to play an important but still poorly defined role in membrane protein biogenesis. Using a variety of different biochemical methods we have obtained evidence that YidC exists in a homooligomeric form similar to that observed for its mitochondrial homolog (a protein called Oxa1p). The results suggest that YidC is a multisubunit complex that could function as a protein conducting channel. In addition, recent results indicate that YidC is freely mobile within the IM and call into question results published by another group suggesting that YidC has a strictly polar localization.

Transcription factors in the nuclear factor ?B (NF-?B) family are evolutionarily conserved master regulators of immune and inflammatory responses. They are activated in response to ligation of many receptors including T-cell receptors, B-cell receptors, members of the tumor necrosis factor (TNF) receptor superfamily and the Toll-like receptor/interleukin-1 receptor (TLR/IL-1R) superfamily. The I?B kinase (IKK), comprising IKKa and IKK, is at the heart of NF-?B activation and mediates two NF-?B activation pathways. The canonical NF-?B pathway is triggered by microbial and viral infections and pro-inflammatory cytokines and is dependent on IKK phosphorylation and activation. The alternative pathway is triggered by certain members of the TNF cytokine family and selectively activates IKKa. Activated IKK phosphorylates I?Bs, leading to their polyubiquitination and subsequent degradation by the proteasome. The freed NF-?B dimers translocate to the nucleus to mediate transcription. Because of its importance in N