PORE FORMATION DOMAIN OF HUMAN PRO-APOPTOTIC BAX INDUCES MAMMALIAN APOPTOSIS AS WELL AS BACTERIAL DEATH WITHOUT ANTAGONIZING ANTI-APOPTOTICFACTORS

A trace amount of the pro-apoptotic factor human Bax was sufficient to kill host Escherichia coli (Asoh, S., Nishimaki, K., Nanbu-Wakao, R., and Ohta, S., submitted). The region of Bax lethal to E. coli cells w as determined by introducing truncated human bar mutant genes. A pepti de corresponding to amino acid residues 115 to 144 of Bax was the smal lest peptide capable of inducing cell death of E. coli. A truncated ba r gene (Bax112-192) containing the region lethal to E. coli was then i ntroduced into a murine promyeloid cell line, FDC-P1. Constitutively e xpressed Bax112-192 induced apoptosis as judged by decrease of transfe ctants surviving and DNA fragmentation. These results indicate that Ba x112-192 contains the region directly responsible for mammalian apopto sis as well as bacterial death. Flow cytometric analysis by FITC-Annex in V showed that the transfectant cells expressing Bax112-192 or nativ e Bax became apoptotic even without external stimuli. The apoptotic po pulation in the cells expressing Bax112-192 was not decreased by co-ex pression of Bcl-2 or Bcl-x(L), while Bcl-2 or Bcl-x(L) sup pressed apo ptosis in the cells expressing native Bax. Therefore, Bax induces apop tosis by its own activity without blocking the anti-apoptotic activity involved in Bcl-2 or Bcl-x(L). (C) 1998 Academic Press.