SIGNAL TRANSDUCTION & TRANSCRIPTION PROTEIN (STAT)

信号转导

• 批准号: 6118310
• 负责人: JAMES E DARNELL
• 金额: $ 0.85万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-10 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6118310
• 关键词: biomedical equipment development; biomedical resource; proteins; spectrometry; technology /technique

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.

Stat1？ 是一种潜在的细胞质转录因子 响应于IFN-（。羧基末端）的酪氨酸磷酸化 38 Stat1的氨基酸？ 需要触发转录和 因此，用作转录激活域（TAD）。 我们是 目前显示了STAT1的TAD？ 可以充当独立 转录激活剂并与特定组相互作用 核蛋白。 丝氨酸727和亮氨酸-724的突变 TAD都降低了转录激活势和 核蛋白的结合。 绑定的蛋白质之一是 确定为MCM5，是MCM家族的成员 DNA复制。 STAT1的体外和体内相互作用？ 证明了MCM5。 此外，体外相互作用 需要保守的Seriene-727，并通过其增强 磷酸化。 MCM5增强的瞬时过表达 STAT1的转录激活？ 在丝氨酸72 7依赖性t中 方式。 最后，在核定水平上的变化在 细胞周期与转录响应的变化相关 ifn-（通过STAT1？在丝氨酸727和亮氨酸724中依赖于 在最佳转录激活中发挥作用的方式。 纸 描述这项工作已被接受供出版。 续。