vMIA, a viral inhibitor of apoptosis targeting mitochondria
vMIA, a viral inhibitor of apoptosis targeting mitochondria
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DOI：
10.1016/s0300-9084(02)01367-6
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发表时间：
2002-02-01
期刊：
影响因子：
3.9
通讯作者：
Goldmacher, VS
中科院分区：
文献类型：
--
作者：
Goldmacher, VS
人巨细胞病毒编码一个强大的细胞死亡抑制因子vMIA（病毒线粒体定位的细胞凋亡抑制剂）。也称为pUL37x1。vMIA是即时早期基因UL37外显子1的产物，主要定位于线粒体，在线粒体中与腺嘌呤核苷酸转位子形成复合物，被认为是线粒体过渡孔复合物的组成部分，vMIA通过阻断线粒体外膜的通透性来抑制细胞凋亡。vMIA的表达保护细胞免受多种刺激引发的凋亡，包括死亡受体的结扎。暴露于某些细胞毒性药物和感染缺乏E1B19K的腺病毒突变体。vMIA的删除突变揭示了其抗凋亡活性所必需和充分的两个结构域。第一个结构域包含线粒体靶向信号。第二域的功能仍然是未知的。vMIA与Bcl-2没有任何显著的氨基酸序列同源性，并且与Bcl-2或Bcl-x(L)不同，它不结合BAX或VDAC。vMIA与Bcl-2之间的这些结构和功能差异表明，vMIA代表了一类独立的细胞死亡抑制因子。对缺乏vMIA的CMV（人巨细胞病毒）突变体的实验提供了强有力的证据，证明vMIA的抗凋亡功能是防止CMV诱导的细胞凋亡所必需的。是病毒复制所必需的。除了vMIA外，UL37还编码两个更长的剪接变异体蛋白gpUL37和GP37(M)。这些蛋白的生物学功能尚未确定，可能与其抗凋亡活性无关。vMIA的鉴定及其抗凋亡功能是CMV复制所必需的，这一发现为开发抗CMV药物提供了理论依据，这些药物可以灭活vMIA，从而恢复CMV感染细胞的凋亡。(C) 2002年法国生物化学和生物分子学会/ Elsevier SAS科学和医学版。版权所有。
Human cytomegalovirus encodes a powerful cell death suppressor vMIA (viral mitochondria-localized inhibitor of apoptosis). also known as pUL37x1. vMIA, a product of the immediate early gene UL37 exon 1, is predominantly localized in mitochondria, where it appears to form a complex with adenine nucleotide translocator, believed to be a component of the mitochondrial transition pore complex, vMIA suppresses apoptosis by blocking permeabilization of the mitochondrial outer membrane. Expression of vMIA protects cells against apoptosis triggered by diverse stimuli, including ligation of death receptors. exposure to certain cytotoxic drugs, and infection with an adenovirus mutant deficient in E1B19K. Deletion mutagenesis of vMIA revealed two domains that are necessary and, together, sufficient for its anti-apoptotic activity. The first domain contains a mitochondrial targeting signal. The function of the second domain is still unknown. vMIA does not share any significant amino acid sequence homology with Bcl-2, and, unlike Bcl-2 or Bcl-x(L), it does not bind BAX or VDAC, These structural and functional differences between vMIA and Bcl-2 suggest that vMIA represents a separate class of cell death suppressors. Experiments with vMIA-deficient CMV (human cytomegalovirus) mutants provide strong evidence that the anti-apoptotic function of vMIA is required to prevent CMV-induced apoptosis. and is necessary for viral replication. In addition to vMIA, UL37 encodes two longer splice-variant proteins, gpUL37 and GP37(M). Biological functions of these proteins have not yet been identified, and may be unrelated to their anti-apoptotic activity. The identification of vMIA and the finding that its anti-apoptotic function is required for CMV replication provides a rationale for the development of anti-CMV pharmaceuticals that would inactivate vMIA and thus restore apoptosis in cells infected with CMV. (C) 2002 Societe francaise de biochimie et biologic moleculaire / Editions scientifiques et medicales Elsevier SAS. All rights reserved.