Involvement of BNIP1 in apoptosis and endoplasmic reticulum membrane fusion
Involvement of BNIP1 in apoptosis and endoplasmic reticulum membrane fusion
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DOI：
10.1038/sj.emboj.7600333
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发表时间：
2004-08-18
期刊：
影响因子：
11.4
通讯作者：
Tagaya, M
中科院分区：
文献类型：
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作者：
Nakajima, K;Hirose, H;Tagaya, M
BNIP 1是BH 3-only蛋白家族的成员，最初被发现是能够与抗凋亡腺病毒E1 B 19-kDa蛋白相互作用的蛋白质之一。在这里，我们公开了一个完全出乎意料的发现，即BNIP 1是包含突触融合蛋白18的复合物的组分，突触融合蛋白18是位于内质网（ER）的可溶性N-乙基马来酰亚胺敏感因子（NSF）附着蛋白（SNAP）受体（SNARE）。功能分析表明，BNIP 1参与ER网络结构的形成，但不参与ER和高尔基体之间的膜运输。值得注意的是，BNIP 1的BH 3结构域中的高度保守的亮氨酸残基不仅在诱导细胞凋亡中起重要作用，而且在α-SNAP的结合中起重要作用，α-SNAP是一种衔接子，用作伴侣ATP酶NSF和SNARE之间的连接。这预示着α-SNAP可能通过与抗凋亡蛋白竞争BNIP 1的BH 3结构域来抑制凋亡。事实上，α-SNAP的过表达显著延迟了星形孢菌素诱导的细胞凋亡。我们的研究结果揭示了明显独立的细胞事件，细胞凋亡和ER膜融合之间可能的串扰。
BNIP1, a member of the BH3-only protein family, was first discovered as one of the proteins that are capable of interacting with the antiapoptotic adenovirus E1B 19-kDa protein. Here we disclose a totally unexpected finding that BNIP1 is a component of the complex comprising syntaxin 18, an endoplasmic reticulum (ER)-located soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptor (SNARE). Functional analysis revealed that BNIP1 participates in the formation of the ER network structure, but not in membrane trafficking between the ER and Golgi. Notably, a highly conserved leucine residue in the BH3 domain of BNIP1 plays an important role not only in the induction of apoptosis but also in the binding of alpha-SNAP, an adaptor that serves as a link between the chaperone ATPase NSF and SNAREs. This predicts that alpha-SNAP may suppress apoptosis by competing with antiapoptotic proteins for the BH3 domain of BNIP1. Indeed, overexpression of alpha-SNAP markedly delayed staurosporine-induced apoptosis. Our results shed light on possible crosstalk between apparently independent cellular events, apoptosis and ER membrane fusion.