Gibson L, Holmgreen S P, Huang D C, Bernard O, Copeland N G, Jenkins N A, Sutherland G R, Baker E, Adams J M, Cory S
Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Victoria, Australia.
Oncogene. 1996 Aug 15;13(4):665-75.
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.
细胞死亡的典型哺乳动物调节因子是bcl-2，这一原癌基因与人类滤泡性淋巴瘤的发生有关。现在已知bcl-2有几个同源物。我们采用基于聚合酶链反应（PCR）的策略克隆了该基因家族的一个新成员，命名为bcl-w。该基因在小鼠和人类之间高度保守，位于小鼠14号染色体中部的T细胞抗原受体α基因附近以及人类14号染色体的q11带。bcl-w的强制表达使淋巴细胞和髓细胞对几种（但不是所有）细胞毒性条件产生抗性。因此，与促进细胞死亡的其他紧密同源物Bax和Bak不同，Bcl-w蛋白与Bcl-2和Bcl-x一样，能促进细胞存活。将Bcl-w的预期氨基酸序列与这些相关蛋白的序列进行比较，有助于确定可能传递存活或抗存活功能的残基。虽然bcl-w在B或T淋巴细胞系中表达不常见，但在所分析的几乎所有小鼠髓细胞系和多种组织中都观察到了该mRNA。这些发现表明bcl-w参与多种细胞类型的凋亡控制。它与bcl-2的功能相似性也使其成为一个有吸引力的候选原癌基因。
