Bcl-G, a novel pro-apoptotic member of the Bcl-2 family

A new member of the Bcl-2 family was identified, Bcl-G, The human BCL-G gen e consists of 6 exons, resides on chromosome 12p12, and encodes two protein s through alternative mRNA splicing, Bcl-G(L) (long) and Bcl-G(S) (short) c onsisting of 327 and 252 amino acids in length, respectively. Bcl-G(L) and Bcl-G(S) have identical sequences for the first 226 amino acids but diverge thereafter. Among the Bcl-2 homology (BH) domains previously recognized in Bcl-2 family proteins, the BH3 domain is found in both Bcl-G(L) and Bcl-G( S), but only the longer Bcl-G(L) protein possesses a BH2 domain. Bcl-G(L) m RNA is expressed widely in adult human tissues, whereas Bcl-G(S) mRNA was f ound only in testis. Overexpression of Bcl-G(L) or Bcl-G(S) in cells induce d apoptosis although Bcl-G(S) was far more potent than Bcl-G(L), Apoptosis induction by Bcl-G(S) depended on the BH3 domain and was suppressed by coex pression of anti-apoptotic Bcl-X-L protein. Bcl-X-L also coimmunoprecipitat ed with Bcl-G(S) but not with mutants of Bcl-G(S) in which the BH3 domain w as deleted or mutated or with Bcl-G(L). Bcl-G(S) was predominantly localize d to cytosolic organelles, whereas Bcl-G(L) was diffusely distributed throu ghout the cytosol. A mutant of Bcl-G(L) in which the BH2 domain was deleted displayed increased apoptotic activity and coimmunoprecipitated with Bcl-X -L, suggesting that the BH2 domain autorepresses Bcl-G(L).