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. 2010 Jun 4;1(5):468–477. doi: 10.1007/s13238-010-0048-4

Beclin 1 cleavage by caspase-3 inactivates autophagy and promotes apoptosis

Yushan Zhu 1,2,✉, Lixia Zhao 1, Lei Liu 1, Ping Gao 1, Weili Tian 2, Xiaohui Wang 1, Haijing Jin 1, Haidong Xu 1, Quan Chen 1,2,✉
PMCID: PMC4875131  PMID: 21203962

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.

Electronic Supplementary Material

Supplementary material is available for this article at 10.1007/s13238-010-0048-4 and is accessible for authorized users.

Keywords: beclin 1, autophagy, apoptosis, caspase cleavage

Electronic supplementary material

13238_2010_48_MOESM1_ESM.pdf (612.6KB, pdf)

Supplementary material, approximately 612 KB.

Footnotes

Electronic Supplementary Material

Supplementary material is available for this article at 10.1007/s13238-010-0048-4 and is accessible for authorized users.

Contributor Information

Yushan Zhu, Email: zhuys@nankai.edu.cn.

Quan Chen, Email: chenquan@nankai.edu.cn.

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Supplementary Materials

13238_2010_48_MOESM1_ESM.pdf (612.6KB, pdf)

Supplementary material, approximately 612 KB.

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