Antiapoptotic function of Bcl-2 in mast cells is dependent on its association with heat shock protein 90beta.
In the present study, we demonstrated that the antiapoptotic function of Bcl-2 in mast cells is significantly dependent on its association with the heat shock protein 90beta (Hsp90beta). Dissociation of these 2 proteins inhibits the antiapoptotic activity of Bcl-2 by initiating the release of cytochrome c from mitochondria into cytosol and increasing the activity of caspase 3 and caspase 7, resulting in mast-cell apoptosis. The antiapoptotic activity of Bcl-2 was greatly affected by knocking-out specifically Hsp90beta using the RNA interference approach. Thus, for the first time, it has been shown that Hsp90beta might modulate the antiapoptotic activity of Bcl-2 at least in mast cells. These findings could have implications for a novel strategy of regulating apoptosis in patients with mastocytosis and other mast cell-associated diseases.
Cohen-Saidon
Cellina
C
Department of Biochemistry, Hebrew University Hadassah Medical School, PO Box 12272, Jerusalem 91120, Israel.
Carmi
Irit
I
Keren
Avishai
A
Razin
Ehud
E
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001854:Bone Marrow Cells; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D018841:HSP90 Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D008407:Mast Cells / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000502:physiology / Q000648:ultrastructure; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018841:HSP90 Heat-Shock Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases