Translocation of TRAF proteins regulates apoptotic threshold of cells

Tumor necrosis factor (TNF) receptor-associated factors (TRAFs) are involve d in signaling pathways triggered by members of the TNF receptor (TNFR) fam ily and other cell surface proteins. After recruitment to a receptor, TRAFs initiate formation of multiprotein complexes that induce downstream events , such as translocation of transcription factor nuclear factor kappa B (NF- kappa B) and activation of c-Sun N-terminal kinase (JNK). Several proteins in these complexes play important roles in regulation of apoptosis. However , the fate of TRAF-containing complexes once assembled in response to recep tor multimerization is not understood. In this report, we demonstrate that crosslinking of TNFR family members or interaction of TRAF2 with the cytopl asmic protein A20 leads to intracellular translocation of TRAF2. This redis tribution leads to depletion of the cytoplasmic pool of TRAF2. The ratio be tween soluble and insoluble TRAF2 determines the sensitivity of cells to TN F-alpha-induced apoptosis and may play an important role in limiting furthe r TRAF-dependent signal transduction. (C) 2000 Academic Press.