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

The Bar gene is a member of the Bcl2 family that functions to regulate the programmed cell death process. A number of Bar isoforms have been previousl y identified: alpha, beta, gamma, delta, and omega. Here we report the iden tification and characterization of an additional fax variant, termed Bare. The newly identified Bar 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 Bar prote in, termed Bax epsilon, which encodes a protein of 164 residues with a calc ulated molecular weight of 18 kDa. The last 69 amino acids of Bax alpha tha t encompass the BH2 and the TM domains are missing in Bax epsilon. The Bax epsilon protein, when expressed as a GST fusion protein, associated efficie ntly with Bax alpha, Bax epsilon, Bcl2, and Bcl-xL. In addition, Bare was a ctive in inducing apoptosis when tested in a transient transfection assay. Furthermore, the presence of antiapoptotic genes including Bcl2, Bcl-xL, an d baculovirus p35 abrogated Bax epsilon and Bax alpha function. Although th e newly identified Bar variant was detectable by RT-PCR in several normal m ouse tissues, the role of this variant in controlling programmed cell death is currently unknown. (C) 1999 Academic Press.