Bcl-2 family member Bcl-G is not a proapoptotic protein

Cell Death Dis. 2012 Oct 11;3(10):e404. doi: 10.1038/cddis.2012.130.


The three major subgroups of the Bcl-2 family, including the prosurvival Bcl-2-like proteins, the proapoptotic Bcl-2 homology (BH)3-only proteins and Bax/Bak proteins, regulate the mitochondrial apoptotic pathway. In addition, some outliers within the Bcl-2 family do not fit into these subgroups. One of them, Bcl-G, has a BH2 and a BH3 region, and was proposed to trigger apoptosis. To investigate the physiological role of Bcl-G, we have inactivated the gene in the mouse and generated monoclonal antibodies to determine its expression. Although two isoforms of Bcl-G exist in human, only one is found in mice. mBcl-G is expressed in a range of epithelial as well as in dendritic cells. Loss of Bcl-G did not appear to affect any of these cell types. mBcl-G only binds weakly to prosurvival members of the Bcl-2 family, and in a manner that is independent of its BH3 domain. To understand what the physiological role of Bcl-G might be, we searched for Bcl-G-binding partners through immunoprecipitation/mass spectroscopy and yeast-two-hybrid screening. Although we did not uncover any Bcl-2 family member in these screens, we found that Bcl-G interacts specifically with proteins of the transport particle protein complex. We conclude that Bcl-G most probably does not function in the classical stress-induced apoptosis pathway, but rather has a role in protein trafficking inside the cell.

MeSH terms

  • Animals
  • Apoptosis
  • HEK293 Cells
  • Humans
  • Immunoprecipitation
  • Mass Spectrometry
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Binding
  • Proto-Oncogene Proteins c-bcl-2 / deficiency
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Two-Hybrid System Techniques
  • Vesicular Transport Proteins / metabolism
  • bcl-2 Homologous Antagonist-Killer Protein / metabolism
  • bcl-2-Associated X Protein / metabolism


  • BCL2L14 protein, mouse
  • Proto-Oncogene Proteins c-bcl-2
  • TRAPPC6B protein, human
  • Vesicular Transport Proteins
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein