bcl-w, a novel member of the bcl-2 family, promotes cell survival

The prototypic mammalian regulator of cell death is Bcl-2, the oncogene implicated in the development of human follicular lymphoma. Several homologues of Bcl-2 are now known. Using a PCR-based strategy we cloned a novel member of this gene family, denoted Bcl-W. The gene, which is highly conserved between mouse and human, resides near the T-cell antigen receptor alpha gene within the central portion of mouse chromosome 14 and on human chromosome 14 at band q11. Enforced expression of Bcl-W rendered lymphoid and myeloid cells refractory to several (but not all) cytotoxic conditions. Thus, like Bcl-2 and Bcl-x, the Bcl-W protein promotes cell survival, in contrast to other close homologues, Bax and Bak, which facilitate cell death. Comparison of the expected amino acid sequence of Bcl-W with that of these relatives helps to delineate residues likely to convey survival or anti-survival function. While expression 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 participates in the control of Apoptosis in multiple cell types. Its functional similarity to Bcl-2 also makes it an attractive candidate proto-oncogene.