成熟的DIABLO/Smac由线粒体内膜上的IMP蛋白酶复合体产生。
Mature DIABLO/Smac is produced by the IMP protease complex on the mitochondrial inner membrane.
作者信息
Burri Lena, Strahm Yvan, Hawkins Christine J, Gentle Ian E, Puryer Michelle A, Verhagen Anne, Callus Bernard, Vaux David, Lithgow Trevor
机构信息
Russell Grimwade School of Biochemistry and Molecular Biology, University of Melbourne, Parkville, VIC 3010, Australia.
出版信息
Mol Biol Cell. 2005 Jun;16(6):2926-33. doi: 10.1091/mbc.e04-12-1086. Epub 2005 Apr 6.
Abstract
DIABLO/Smac is a mitochondrial protein that can promote apoptosis by promoting the release and activation of caspases. To do so, DIABLO/Smac must first be processed by a mitochondrial protease and then released into the cytosol, and we show this in an intact cellular system. We propose that the precursor form of DIABLO/Smac enters the mitochondria through a stop-transfer pathway and is processed to its active form by the inner membrane peptidase (IMP) complex. Catalytic subunits of the mammalian IMP complex were identified based on sequence conservation and functional complementation, and the novel sequence motif RX(5)P in Imp1 and NX(5)S in Imp2 distinguish the two catalytic subunits. DIABLO/Smac is one of only a few specific proteins identified as substrates for the IMP complex in the mitochondrial intermembrane space.
摘要
DIABLO/Smac是一种线粒体蛋白，它可通过促进半胱天冬酶的释放和激活来促进细胞凋亡。为此，DIABLO/Smac必须首先由一种线粒体蛋白酶进行加工，然后释放到细胞质中，而我们在完整的细胞系统中证实了这一点。我们提出，DIABLO/Smac的前体形式通过一种停止转移途径进入线粒体，并由内膜肽酶（IMP）复合体加工成其活性形式。基于序列保守性和功能互补性鉴定出了哺乳动物IMP复合体的催化亚基，Imp1中的新型序列基序RX(5)P和Imp2中的NX(5)S区分了这两个催化亚基。DIABLO/Smac是仅有的几种被确定为线粒体内膜间隙中IMP复合体底物的特定蛋白之一。
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本文引用的文献
1
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J Biol Chem. 2004 Sep 3;279(36):37588-96. doi: 10.1074/jbc.M401408200. Epub 2004 Jun 16.
2
Toxic proteins released from mitochondria in cell death.细胞死亡时线粒体释放的毒性蛋白。
Oncogene. 2004 Apr 12;23(16):2861-74. doi: 10.1038/sj.onc.1207523.
3
Structural and functional characterization of mitochondrial EndoG, a sugar non-specific nuclease which plays an important role during apoptosis.线粒体核酸内切酶G的结构与功能特性，一种在细胞凋亡过程中起重要作用的非糖特异性核酸酶。
J Mol Biol. 2004 Apr 23;338(2):217-28. doi: 10.1016/j.jmb.2004.02.069.
4
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Mol Biol Evol. 2004 Apr;21(4):652-8. doi: 10.1093/molbev/msh058. Epub 2004 Jan 22.
5
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6
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Brain. 2003 Aug;126(Pt 8):1814-20. doi: 10.1093/brain/awg174. Epub 2003 Jun 4.
7
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Biochem Biophys Res Commun. 2003 May 9;304(3):487-97. doi: 10.1016/s0006-291x(03)00621-1.
8
Biogenesis of yeast mitochondrial cytochrome c: a unique relationship to the TOM machinery.
J Mol Biol. 2003 Mar 21;327(2):465-74. doi: 10.1016/s0022-2836(03)00118-9.
9
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J Cell Biol. 2002 Dec 23;159(6):923-9. doi: 10.1083/jcb.200207071. Epub 2002 Dec 16.
10
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Chem Rev. 2002 Dec;102(12):4549-80. doi: 10.1021/cr010166y.
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