We report the isolation of bcl-x, a bcl-2-related gene that can functi
on as a bcl-2-independent regulator of programed cell death (apoptosis
). Alternative splicing results in two distinct bcl-x mRNAs. The prote
in product of the larger mRNA, bcl-x(L), is similar in size and predic
ted structure to Bcl-2. When stably transfected into an IL-3-dependent
cell line, bcl-x(L) inhibits cell death upon growth factor with drawa
l at least as well as bcl-2. Surprisingly, the second mRNA species, bc
l-x(s), encodes a protein that inhibits the ability of bcl-2 to enhanc
e the survival of growth factor-deprived cells. In vivo, bcl-x(s) mRNA
is expressed at high levels in cells that undergo a high rate of turn
over, such as developing lymphocytes. In contrast, bcl-x(L) is found i
n tissues containing long-lived postmitotic cells, such as adult brain
. Together these data suggest that bcl-x plays an important role in bo
th positive and negative regulation of programed cell death.