Autophagy and apoptosis are both highly regulated biological processes that play essential roles in tissue homeostasis,development and diseases.Autophagy is also described as a mechanism of death pathways,however,the ...Autophagy and apoptosis are both highly regulated biological processes that play essential roles in tissue homeostasis,development and diseases.Autophagy is also described as a mechanism of death pathways,however,the precise mechanism of how autophagy links to cell death remains to be fully understood.Beclin 1 is a dual regulator for both autophagy and apoptosis.In this study we found that Beclin 1 was a substrate of caspase-3 with two cleavage sites at positions 124 and 149,respectively.Furthermore,the autophagosome formation occurred,followed by the appearance of morphological hallmarks of apoptosis after staurosporine treatment.The cleavage products of Beclin 1 reduced autophagy and promoted apoptosis in HeLa cells and the cells in which Beclin 1 was stably knocked down by specific shRNA.In addition,the cleavage of Beclin 1 resulted in abrogating the interaction between Bcl-2 with Beclin 1,which could be blocked by z-VAD-fmk.Thus,our results suggest that the cleavage of Beclin 1 by caspase-3 may contribute to inactivate autophagy leading towards augmented apoptosis.展开更多
基金This work was supported by the National Basic Research Program(973 program project)(grants Nos.2007CB914800,2006CB910102)grants from National Natural Science Foundation of China(grant Nos.30630038 and 30400098)+1 种基金grants from Tianjin Natural Science foundation(09JCZDJC21200)to Y.Zhua project grant from Chinese Academy of Sciences KSCX2-YW-R-02 to Q.Chen.
文摘Autophagy and apoptosis are both highly regulated biological processes that play essential roles in tissue homeostasis,development and diseases.Autophagy is also described as a mechanism of death pathways,however,the precise mechanism of how autophagy links to cell death remains to be fully understood.Beclin 1 is a dual regulator for both autophagy and apoptosis.In this study we found that Beclin 1 was a substrate of caspase-3 with two cleavage sites at positions 124 and 149,respectively.Furthermore,the autophagosome formation occurred,followed by the appearance of morphological hallmarks of apoptosis after staurosporine treatment.The cleavage products of Beclin 1 reduced autophagy and promoted apoptosis in HeLa cells and the cells in which Beclin 1 was stably knocked down by specific shRNA.In addition,the cleavage of Beclin 1 resulted in abrogating the interaction between Bcl-2 with Beclin 1,which could be blocked by z-VAD-fmk.Thus,our results suggest that the cleavage of Beclin 1 by caspase-3 may contribute to inactivate autophagy leading towards augmented apoptosis.
