Y. Ishibashi et al., PORE FORMATION DOMAIN OF HUMAN PRO-APOPTOTIC BAX INDUCES MAMMALIAN APOPTOSIS AS WELL AS BACTERIAL DEATH WITHOUT ANTAGONIZING ANTI-APOPTOTICFACTORS, Biochemical and biophysical research communications, 243(2), 1998, pp. 609-616
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.