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Blood, 15 February 2006, Vol. 107, No. 4, pp. 1413-1420.
Prepublished online as a Blood First Edition Paper on September 15, 2005; DOI 10.1182/blood-2005-07-2648.
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Submitted July 5, 2005
Accepted September 6, 2005
The anti-apoptotic function of Bcl-2 in mast cells is dependent on its association with Heat Shock Protein 90
Cellina Cohen-Saidon, Irit Carmi, Avishai Keren, and Ehud Razin*
Department of Biochemistry, Hebrew University Hadassah Medical School, POB 12272, Jerusalem, Israel
* Corresponding author; email: ehudr{at}cc.huji.ac.il.
In the present study we demonstrated that the anti-apoptotic function of Bcl-2 in mast cells is significantly dependent upon its association with the heat shock protein 90 (Hsp90 ). Dissociation of these two proteins inhibits the anti-apoptotic activity of Bcl-2 by initiating release of cytochrome C from mitochondria into cytosol and increasing activity of caspase 3 and caspase 7, resulting in mast cells apoptosis. The anti-apoptotic activity of Bcl-2 was greatly affected by knocking-out specifically Hsp90 using the RNA interference approach.
Thus, for the first time it has been shown that Hsp90 might modulate the anti-apoptotic activity of Bcl-2 at least in mast cells. These findings could implicate for a novel strategy of regulating apoptosis in mastocytotic patients and other mast cells associated diseases.

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