MODULATION OF ENDOPLASMIC-RETICULUM CALCIUM-PUMP BY BCL-2

Members of the bcl-2 gene family encode proteins that function either to promote or to inhibit apoptosis. Despite numerous efforts, the mech anism of action of Bcl-2, an anti-apoptotic protein, is still not clea r. In particular, the relation between Bcl-2 and the endoplasmic retic ulum (ER) calcium store is not well-understood. In the present work, w e examined the effect of Bcl-2 on the ER store. We demonstrate that ov erexpression of Bcl-2 in breast epithelial cells modulates ER store by upregulating calcium pump (SERCA) expression,without affecting the re lease channel (IP3R). The steady state levels of SERCA2 mRNA and prote in were both increased in Bcl-2 expression clones. The increase in SER CA2 protein leads to accelerated calcium uptake and enhanced Ca2+ load ing. In addition, we also show the detection of intracellular interact ion between Bcl-2 and SERCA molecules by co-immunoprecipitation. Since high lumenal Ca2+ concentration of ER is essential for normal cell fu nctions, the results suggest that Bcl-2 preserves the ER Ca2+ store by upregulating SERCA gene expression as well as by a possible interacti on with the pump.