SIGNAL TRANSDUCTION & TRANSCRIPTION PROTEIN (STAT)

STAT1？是一种潜在的细胞质转录因子，由 干扰素对酪氨酸磷酸化的影响。羧基末端 38个氨基酸的STAT1？需要触发转录和 因此作为转录激活结构域(TAD)。我们是 目前显示TAD的STAT1？可以作为独立的 转录激活剂，并与特定的群体相互作用 核蛋白。银屑病患者丝氨酸-727和亮氨酸-724突变 TAD既能降低转录激活电位，又能降低细胞周期。 核蛋白的结合。其中一个结合蛋白是 确认为MCM5，参与印心的MCM家族成员 DNA复制。STAT1？ 和MCM5。此外，体外相互作用 需要保守的Serene-727，并通过其增强 磷酸化。MCM5基因的瞬时过表达增强 STAT1转录激活？在丝氨酸72 7依赖的T细胞中 举止。最后，核结合MCM5水平的变化 细胞周期与转录反应的变化相关 干扰素-(通过STAT1？在丝氨酸-727和亮氨酸724依赖中 在最佳转录激活中发挥作用的方式。一篇论文 对这项工作的描述已被接受出版。继续。

Stat1? is a latent cytoplasmic transcription factor activated by tyrosine phosphorylation in response to IFN-(. The carboxyl terminal 38 amino acids of Stat1? are required to trigger transcription and therefore serve as a transcription activation domain (TAD). We are currently showing that the TAD of Stat1? can act as an independent transcriptional activator and that it interacts with a specific group of nuclear proteins. Mutation of serine-727 and leucine-724 in the TAD both decrease the transcriptional activation potential and the binding of the nuclear proteins. One of the bound proteins was identified as MCM5, a member of the MCM family involved in initiation of DNA replication. Both in vitro and in vivo interaction of Stat1? and MCM5 were demonstrated. Moreover the in vitro interaction required the conserved seriene-727 and was enhanced by its phosphorylation. Transient over-expression of MCM5 enhanced transcriptional activation by Stat1? in a serine 72 7-dependen t manner. Finally, changes in the level of nucle bound MCM5 during the cell cycle correlated with the changes in transcriptional response to IFN-( acting through Stat1? in a serine-727 and leucine 724-dependent manner to play a role in optimal transcriptional activation. A paper describing this work has been accepted for publication. Cont.