title: Beclin 1 cleavage by caspase-3 inactivates autophagy and promotes apoptosis.
abstract: 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.
authors.affiliation: The Joint Laboratory of Apoptosis and Cancer Biology, College of Life Sciences, Nankai University, Tianjin 300071, China. zhuys@nankai.edu.cn
authors.forename: Yushan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Lixia
authors.initials: L
authors.lastname: Zhao
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Ping
authors.initials: P
authors.lastname: Gao
authors.forename: Weili
authors.initials: W
authors.lastname: Tian
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.forename: Haijing
authors.initials: H
authors.lastname: Jin
authors.forename: Haidong
authors.initials: H
authors.lastname: Xu
authors.forename: Quan
authors.initials: Q
authors.lastname: Chen
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy; D000071186:Beclin-1; D053148:Caspase 3 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D053148:Caspase 3