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中介体上一个新的对接位点对于病毒蛋白16(VP16)在哺乳动物细胞中的激活作用至关重要。

A novel docking site on Mediator is critical for activation by VP16 in mammalian cells.

作者信息

Mittler Gerhard, Stühler Thomas, Santolin Lisa, Uhlmann Thomas, Kremmer Elisabeth, Lottspeich F, Berti Lucia, Meisterernst Michael

机构信息

National Research Center for Environment and Health-GSF, Institute of Molecular Immunology, Gene Expression, Marchionini-Strasse 25, D-81377 Munich, Germany.

出版信息

EMBO J. 2003 Dec 15;22(24):6494-504. doi: 10.1093/emboj/cdg619.

Abstract

ARC92/ACID1 was identified as a novel specific target of the herpes simplex transactivator VP16 using an affinity purification procedure. Characterization of the protein revealed tight interactions with human Mediator mediated through a von Willebrand type A domain. ARC92/ACID1 further contains a novel activator-interacting domain (ACID), which it shares with at least one other human gene termed PTOV1/ACID2. The structure of ARC92/ACID1 is of ancient origin but is conserved in mammals and in selected higher eukaryotes. A subpopulation of Mediator is associated with ARC92/ACID1, which is specifically required for VP16 activation both in vitro and in mammalian cells, but is dispensable for other activators such as SP1. Despite many known targets of VP16, ARC92/ACID1 appears to impose a critical control on transcription activation by VP16 in mammalian cells.

摘要

通过亲和纯化程序,ARC92/ACID1被鉴定为单纯疱疹病毒反式激活因子VP16的一种新型特异性靶标。对该蛋白质的表征揭示了其通过A型血管性血友病因子结构域与人类中介体紧密相互作用。ARC92/ACID1还包含一个新型激活因子相互作用结构域(ACID),它与至少另一个称为PTOV1/ACID2的人类基因共有该结构域。ARC92/ACID1的结构起源古老,但在哺乳动物和选定的高等真核生物中保守。中介体的一个亚群与ARC92/ACID1相关联,这在体外和哺乳动物细胞中对于VP16激活都是特异性必需的,但对于其他激活因子如SP1则是可有可无的。尽管VP16有许多已知靶标,但ARC92/ACID1似乎对哺乳动物细胞中VP16的转录激活施加关键控制。

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