Identification and characterization of Baxε, a novel Bax variant missing the BH2 and the transmembrane domains

The Bax gene is a member of the Bcl2 family that functions to regulate the programmed cell death process. A number of Bax isoforms have been previously identified: alpha, beta, gamma, delta, and omega. Here we report the identification and characterization of an additional fax variant, termed Bare. The newly identified Bax variant contains a 97-base insertion generated by alternative splicing which includes a previously unidentified exon between exons 4 and 5. The insertion causes the production of a truncated Bax protein, termed Bax epsilon, which encodes a protein of 164 residues with a calculated molecular weight of 18 kDa. The last 69 amino acids of Bax alpha that encompass the BH2 and the TM domains are missing in Bax epsilon. The Bax epsilon protein, when expressed as a GST fusion protein, associated efficiently with Bax alpha, Bax epsilon, Bcl2, and Bcl-xL. In addition, Bare was active in inducing apoptosis when tested in a transient transfection assay. Furthermore, the presence of antiapoptotic genes including Bcl2, Bcl-xL, and baculovirus p35 abrogated Bax epsilon and Bax alpha function. Although the newly identified Bax variant was detectable by RT-PCR in several normal mouse tissues, the role of this variant in controlling programmed cell death is currently unknown. (C) 1999 Academic Press.