Serotype-specific reorganization of the Mre11 complex by adenoviral E4orf3 proteins.
Serotype-specific reorganization of the Mre11 complex by adenoviral E4orf3 proteins.
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腺病毒 E4orf3 蛋白对 Mre11 复合物进行血清型特异性重组。
DOI：
10.1128/jvi.79.11.6664-6673.2005
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发表时间：
2005
影响因子：
5.4
通讯作者：
Weitzman,MatthewD
中科院分区：
文献类型：
--
作者：
Stracker,TravisH;Lee,DarwinV;Carson,ChristianT;Araujo,FelipeD;Ornelles,DavidA;Weitzman,MatthewD
5型腺病毒（Ad 5）的早期转录区4（E4）编码调节剪接、凋亡、转录、DNA复制和修复途径的基因产物。缺乏E4 orf 3和E4 orf 6的病毒具有严重的复制缺陷，部分特征在于形成基因组多联体。多联体的形成依赖于细胞Mre 11复合物，并被E4 orf 3和E4 orf 6蛋白阻止。Mre 11/Rad 50/Nbs 1蛋白被Ad 5病毒E1 b55 K/E4 orf 6复合物靶向用于蛋白酶体介导的降解。Ad 5 E4 orf 3的表达导致Mre 11复合体成员的重新分布，并导致它们被排除在病毒复制中心之外。在这项研究中，我们进一步分析了来自不同腺病毒血清型的E4蛋白与Mre 11复合物的相互作用。对血清型Ad 4和Ad 12感染的分析表明，Mre 11/Rad 50/Nbs 1蛋白的降解是E1 b55 K/E4 orf 6复合物的保守特征。令人惊讶的是，Nbs 1和Rad 50定位于Mre 11复合物降解之前的Ad 4和Ad 12病毒的复制中心。Ad 4和Ad 12的E4 orf 3蛋白的表达载体的转染没有改变Mre 11复合物成员的定位。Ad 4和Ad 12的E4 orf 3蛋白也未能补充缺失E4的病毒的多联体形成和后期蛋白质产生中的缺陷。这些结果揭示了来自不同血清型的高度保守的E4 orf 3蛋白在破坏Mre 11复合物的能力方面的惊人差异。
The early transcriptional region 4 (E4) of adenovirus type 5 (Ad5) encodes gene products that modulate splicing, apoptosis, transcription, DNA replication, and repair pathways. Viruses lacking both E4orf3 and E4orf6 have a severe replication defect, partially characterized by the formation of genome concatemers. Concatemer formation is dependent upon the cellular Mre11 complex and is prevented by both the E4orf3 and E4orf6 proteins. The Mre11/Rad50/Nbs1 proteins are targeted for proteasome-mediated degradation by the Ad5 viral E1b55K/E4orf6 complex. The expression of Ad5 E4orf3 causes a redistribution of Mre11 complex members and results in their exclusion from viral replication centers. For this study, we further analyzed the interactions of E4 proteins from different adenovirus serotypes with the Mre11 complex. Analyses of infections with serotypes Ad4 and Ad12 demonstrated that the degradation of Mre11/Rad50/Nbs1 proteins is a conserved feature of the E1b55K/E4orf6 complex. Surprisingly, Nbs1 and Rad50 were localized to the replication centers of both Ad4 and Ad12 viruses prior to Mre11 complex degradation. The transfection of expression vectors for the E4orf3 proteins of Ad4 and Ad12 did not alter the localization of Mre11 complex members. The E4orf3 proteins of Ad4 and Ad12 also failed to complement defects in both concatemer formation and late protein production of a virus with a deletion of E4. These results reveal surprising differences among the highly conserved E4orf3 proteins from different serotypes in the ability to disrupt the Mre11 complex.