Bcl-2 proteins and calcium signaling: complexity beneath the surface.

摘要: Antiapoptotic Bcl-2-family members are well known for their 'mitochondrial' functions as critical neutralizers of proapoptotic members, including the executioner multidomain proteins Bax and Bak BH3-only proteins. It has been clear more than 20 years that Bcl-2 can impact intracellular Ca(2+) homeostasis dynamics. Moreover, altered signaling is increasingly linked to oncogenic behavior. Specifically targeting Ca(2+)-signaling machinery may thus prove be a valuable strategy cancer treatment. Over 10 ago major controversy was recognized concerning whether or not exerted antiapoptotic via through lowering filling state endoplasmic reticulum (ER) stores by suppressing release from ER without affecting this store. Further research different laboratories indicated wide variety mechanisms which signaling. In review, we propose multimodal regulators events in cell survival death. We will discuss how death regulating transport systems at ER, mitochondria plasma membrane impacting organization organelles these insights exploited causing cells. Finally, existing reflects diversity links between signaling, certainly all targets operative every type condition.