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 gene consists of 6 exons, resides on chromosome 12p12, and encodes two proteins through alternative mRNA splicing, Bcl-G(L) (long) and Bcl-G(S) (short) consisting 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) mRNA is expressed widely in adult human tissues, whereas Bcl-G(S) mRNA was found only in testis. Overexpression of Bcl-G(L) or Bcl-G(S) in cells induced 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 coexpression of anti-apoptotic Bcl-X(L) protein. Bcl-X(L) also coimmunoprecipitated with Bcl-G(S) but not with mutants of Bcl-G(S) in which the BH3 domain was deleted or mutated or with Bcl-G(L). Bcl-G(S) was predominantly localized to cytosolic organelles, whereas Bcl-G(L) was diffusely distributed throughout 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).
Guo
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Burnham Institute, La Jolla, California 92037, USA.
Godzik
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Reed
J C
JC
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D017209:Apoptosis / Q000235:genetics*; D002451:Cell Compartmentation; D002878:Chromosomes, Human, Pair 1; D003600:Cytosol; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons; D019254:Genes, bcl-2; D006801:Humans; D008969:Molecular Sequence Data; D015388:Organelles; D017434:Protein Structure, Tertiary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D017422:Sequence Analysis, DNA
C428448:BCL2L14 protein, human; D018076:DNA, Complementary; D019253:Proto-Oncogene Proteins c-bcl-2