Evidence for existence of an apoptosis-inducing BH3-only protein, sayonara, in Drosophila.

Evidence for existence of an apoptosis-inducing BH3-only protein, sayonara, in Drosophila.
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DOI:
10.15252/embj.2021110454
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发表时间:
2023-04-17
期刊:
影响因子:
11.4
通讯作者:
Yoo, Sa Kan
Yoo, Sa Kan
中科院分区:
生物学1区
文献类型:
--
作者:
Ikegawa, Yuko;Combet, Christophe;Groussin, Mathieu;Navratil, Vincent;Safar-Remali, Sabrina;Shiota, Takuya;Aouacheria, Abdel;Yoo, Sa Kan

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细胞需要感知压力来启动休眠细胞死亡程序的执行。自从第一个BH3-Only蛋白Bad被发现以来,BH3-Only蛋白一直被认为是诱导细胞凋亡不可或缺的应激感受器。到目前为止,在果蝇中还没有发现仅有BH3的蛋白质,尽管它们在其他生物中很重要。在这里,我们鉴定了第一个果蝇BH3-Only蛋白质,并将其命名为Sayonara。Sayonara以BH3基序依赖的方式诱导细胞凋亡,并与bcl2同源蛋白Buffy和Debc1在基因和生化上相互作用。Sayonara介导的caspase激活和自噬之间存在正反馈循环。Sayonara的BH3基序在祖先基因复制导致双翅目谱系中形成Buffy和Debcl时出现。据我们所知,这是首次在果蝇中鉴定出真正的BH3蛋白,从而为细胞死亡机制如何随时间和跨分类群进化提供了一个独特的例子。第一个果蝇BH3-Only蛋白Sayonara的鉴定表明,它通过与bcl2同源物相互作用而在诱导细胞凋亡中发挥作用。
Cells need to sense stresses to initiate the execution of the dormant cell death program. Since the discovery of the first BH3‐only protein Bad, BH3‐only proteins have been recognized as indispensable stress sensors that induce apoptosis. BH3‐only proteins have so far not been identified in Drosophila despite their importance in other organisms. Here, we identify the first Drosophila BH3‐only protein and name it sayonara. Sayonara induces apoptosis in a BH3 motif‐dependent manner and interacts genetically and biochemically with the BCL‐2 homologous proteins, Buffy and Debcl. There is a positive feedback loop between Sayonara‐mediated caspase activation and autophagy. The BH3 motif of sayonara phylogenetically appeared at the time of the ancestral gene duplication that led to the formation of Buffy and Debcl in the dipteran lineage. To our knowledge, this is the first identification of a bona fide BH3‐only protein in Drosophila, thus providing a unique example of how cell death mechanisms can evolve both through time and across taxa. Identification of the first Drosophila BH3‐only protein, sayonara, demonstrates its role in induction of apoptosis via interaction with BCL‐2 homologs.
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