Bcl-G, a Novel Pro-apoptotic Member of the Bcl-2 Family*
Abstract
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-GL (long) and Bcl-GS (short) consisting of 327 and 252 amino acids in length, respectively. Bcl-GL and Bcl-GS 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-GL and Bcl-GS, but only the longer Bcl-GL protein possesses a BH2 domain. Bcl-GLmRNA is expressed widely in adult human tissues, whereas Bcl-GS mRNA was found only in testis. Overexpression of Bcl-GL or Bcl-GS in cells induced apoptosis although Bcl-GS was far more potent than Bcl-GL. Apoptosis induction by Bcl-GS depended on the BH3 domain and was suppressed by coexpression of anti-apoptotic Bcl-XL protein. Bcl-XL also coimmunoprecipitated with Bcl-GS but not with mutants of Bcl-GS in which the BH3 domain was deleted or mutated or with Bcl-GL. Bcl-GS was predominantly localized to cytosolic organelles, whereas Bcl-GL was diffusely distributed throughout the cytosol. A mutant of Bcl-GL in which the BH2 domain was deleted displayed increased apoptotic activity and coimmunoprecipitated with Bcl-XL, suggesting that the BH2 domain autorepresses Bcl-GL.
- BH
- Bcl-2 homology domain
- EST
- expressed sequence tag
- RACE
- rapid amplification of cDNA ends
- PCR
- polymerase chain reaction
- RT-PCR
- reverse transcription-PCR
- GFP
- green fluorescent protein
- PKA
- cAMP-dependent kinase
- PKC
- protein kinase C
- UTR
- untranslated region
- Received July 5, 2000.
- Revision received October 10, 2000.
- The American Society for Biochemistry and Molecular Biology, Inc.
