The involvement of Bcl-2 in mast cell apoptosis.
Apoptosis or programmed cell death plays an important role in a wide variety of physiological processes. Apoptosis is regulated by proteins of the Bcl-2 family consisting of both anti-apoptotic and pro-apoptotic factors. The direct involvement of the Bcl-2 protein family in the process of mast cell apoptosis has not been clarified. We have used a single-chain antibody (scFv) raised against Bcl-2 derived from human phage-display antibody library. The addition of TAT sequence, which is responsible for translocation through the membrane, endows the anti-Bcl-2-scFv with the ability to penetrate living cells. The association of anti-Bcl-2-scFv-TAT with intracellular Bcl-2 leads to neutralization of Bcl-2 and eradication of its anti-apoptotic activity in two types of mast cells and in a human breast cancer cell line. Moreover, we found by mass spectrometry and co-immunoprecipitation assay that heat shock protein 90b (Hsp90b) forms a complex with Bcl-2 in mast cells. Thus, understanding the network of interactions between Bcl-2 and non-Bcl-2 family members might help in development of more specific drugs and cancer therapy.
Cohen-Saidon
Cellina
C
Department of Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
Razin
Ehud
E
D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008407:Mast Cells / Q000166:cytology / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*
D018841:HSP90 Heat-Shock Proteins; D019253:Proto-Oncogene Proteins c-bcl-2