BCL-W, A NOVEL MEMBER OF THE BCL-2 FAMILY, PROMOTES CELL-SURVIVAL

The prototypic mammalian regulator of cell death is bcl-2, the oncogen e implicated in the development of human follicular lymphoma. Several homologues of bcl-2 are now known. Using a PCR-based strategy we clone d a novel member of this gene family, denoted bcl-w. The gene, which i s highly conserved between mouse and human, resides near the T-cell an tigen receptor a gene within the central portion of mouse chromosome 1 4 and on human chromosome 14 at band q11. Enforced expression of bcl-w rendered lymphoid and myeloid cells refractory to several (but not al l) cytotoxic conditions. Thus, like Bcl-2 and Bcl-x, the Bcl-w protein promotes cell survival, in contrast to other close homologues, Bar an d Bak, which facilitate cell death. Comparison of the expected amino a cid sequence of Bcl-w with that of these relatives helps to delineate residues likely to convey survival or anti-survival function. While ex pression of bcl-w was uncommon in B or T lymphoid cell lines, the mRNA was observed in almost all murine myeloid cell lines analysed and in a wide range of tissues. These findings suggest that bcl-w participate s in the control of apoptosis in multiple cell types. Its functional s imilarity to bcl-2 also makes it an attractive candidate proto-oncogen e.