Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
Cell Signal. 2010 Jun;22(6):883-7. doi: 10.1016/j.cellsig.2009.12.005. Epub 2009 Dec 30.
The interferon regulatory factors (IRFs) play important roles in development of the immune system and host defense. Recent crystallographic and biochemical studies have provided insights into the mechanism of activation of IRFs by phosphorylation. The activation of a latent closed conformation of IRF in the cytoplasm is triggered by phosphorylation of Ser/Thr residues in a C-terminal region. Phosphorylation stimulates the C-terminal autoinhibitory domain to attain a highly extended conformation triggering dimerization through extensive contacts to a second subunit. Dimers are then transported into the nucleus and assemble with the coactivator CBP/p300 to activate transcription of type I interferons and other target genes. The advances made in understanding the release of inhibition after IRF dimerization have generated a detailed structural model of how IRFs signaling pathways are activated.
干扰素调节因子（IRFs）在免疫系统发育和宿主防御中发挥重要作用。最近的晶体学和生化研究为 IRF 通过磷酸化激活的机制提供了深入的了解。IRF 细胞质中潜伏的封闭构象的激活是由 C 末端区域中丝氨酸/苏氨酸残基的磷酸化触发的。磷酸化刺激 C 末端自身抑制结构域达到高度伸展的构象，通过与第二个亚基的广泛接触触发二聚化。然后二聚体被运送到细胞核中，并与共激活因子 CBP/p300 组装，以激活 I 型干扰素和其他靶基因的转录。在理解 IRF 二聚化后抑制释放方面的进展，为 IRF 信号通路的激活提供了一个详细的结构模型。
