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， 酪氨酸磷酸化响应IFN-（. 羧基末端 Stat1？ 需要触发转录， 因此充当转录激活结构域（transcription activation domain，ESTs）。 我们 目前显示，Stat 1？ 可以作为独立的 转录激活因子，并与特定的基团相互作用 核蛋白。 丝氨酸-727和亮氨酸-724突变在大肠癌中的作用 这两种酶都降低了转录激活潜力， 核蛋白的结合。 其中一种结合蛋白是 鉴定为MCM 5，其为参与启动的MCM家族的成员 DNA复制。 在体外和体内的相互作用的Stat 1？ 和MCM 5进行了验证。 此外，体外相互作用 需要保守的seriene-727，并通过其 磷酸化 MCM 5的瞬时过表达增强 转录激活Stat 1？ 在丝氨酸72 7依赖性测试中 方式 最后，核结合MCM 5水平的变化， 细胞周期与转录反应的变化相关， IFN-（通过Stat 1？ 在丝氨酸727和亮氨酸724依赖性 在最佳转录激活中发挥作用的方式。 一篇论文 描述这项工作已被接受出版。 续