SIGNAL TRANSDUCTION & TRANSCRIPTION PROTEIN (STAT)

Stat1吗?潜伏的细胞质转录因子是否被激活

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.