BCL-X, A BCL-2-RELATED GENE THAT FUNCTIONS AS A DOMINANT REGULATOR OF APOPTOTIC CELL-DEATH

We report the isolation of bcl-x, a bcl-2-related gene that can function as a bcl-2-independent regulator of programed cell death (apoptosis). Alternative splicing results in two distinct bcl-x mRNAs. The protein product of the larger mRNA, bcl-x(L), is similar in size and predicted structure to Bcl-2. When stably transfected into an IL-3-dependent cell line, bcl-x(L) inhibits cell death upon growth factor with drawal at least as well as bcl-2. Surprisingly, the second mRNA species, bcl-x(s), encodes a protein that inhibits the ability of bcl-2 to enhance 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 turnover, such as developing lymphocytes. In contrast, bcl-x(L) is found in tissues containing long-lived postmitotic cells, such as adult brain. Together these data suggest that bcl-x plays an important role in both positive and negative regulation of programed cell death.