Bacterial death induced by expression of the intracellular portion of human Fas

Abstract

In attempting to produce the intracellular portion of human Fas (IC175-319) as a GST-fusion protein we found that expression of GSTIC175-319, but not GST alone or GST-IC231-298 (containing the Fas death domain), rapidly caused the death of host E. coli cells. Expression of GST-IC175-319 with a single amino acid substitution (V238N) corresponding to the mouse Ipr(cg) mutation, or E245A, which abolishes the ability of Fas to self-associate, did not kill bacteria. Deletional analysis identified a 20-amino acids region (Asp210-Lys230 as essential for the killing activity, and introduction of a single amino acid substitution (T225P) in this 20 amino acid region markedly decreased the ability of Fas-IC175-319 to cause bacterial death. These data indicate that Fas can deliver a death signal in prokaryotic organisms by a means that shares some features with eukaryotic cells, and raise the possibility that certain mechanisms leading to programmed cell death may be conserved from bacteria to mammalian cells.