Mittler Gerhard, Stühler Thomas, Santolin Lisa, Uhlmann Thomas, Kremmer Elisabeth, Lottspeich F, Berti Lucia, Meisterernst Michael
National Research Center for Environment and Health-GSF, Institute of Molecular Immunology, Gene Expression, Marchionini-Strasse 25, D-81377 Munich, Germany.
EMBO J. 2003 Dec 15;22(24):6494-504. doi: 10.1093/emboj/cdg619.
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.
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。