title: A novel role for synaptic acetylcholinesterase as an apoptotic deoxyribonuclease.
abstract: In addition to terminating neurotransmission by hydrolyzing acetylcholine, synaptic acetylcholinesterase (AChES) has been found to have a pro-apoptotic role. However, the underlying mechanism has rarely been investigated. Here, we report a nuclear translocation-dependent role for AChES as an apoptotic deoxyribonuclease (DNase). AChES polypeptide binds to and cleaves naked DNA at physiological pH in a Ca(2+)-Mg(2+)-dependent manner. It also cleaves chromosomal DNA both in pre-fixed and in apoptotic cells. In the presence of a pan-caspase inhibitor, the cleavage still occurred after nuclear translocation of AChES, implying that AChES-DNase acts in a CAD- and EndoG-independent manner. AChE gene knockout impairs apoptotic DNA cleavage; this impairment is rescued by overexpression of the wild-type but not (aa 32-138)-deleted AChES. Furthermore, in comparison with the nuclear-localized wild-type AChES, (aa 32-138)-deleted AChES loses the capacity to initiate apoptosis. These observations confirm that AChES mediates apoptosis via its DNase activity.
authors.affiliation: The State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai, China.
authors.forename: Aiying
authors.initials: A
authors.lastname: Du
authors.affiliation: The State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.affiliation: The State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai, China.
authors.forename: Kaijie
authors.initials: K
authors.lastname: Guo
authors.affiliation: The State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: The State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai, China.
authors.forename: Yihan
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Fudan University , Shanghai, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: OuYang
authors.affiliation: The State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai, China.
authors.forename: Xuejin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Niu
authors.affiliation: The State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.affiliation: The State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: The State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai, China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Zhang
keywords: DNA cleavage; DNA-binding protein; apoptosis; deoxyribonuclease; nuclear translocation; synaptic acetylcholinesterase