Timofeeva Olga A, Tarasova Nadya I
Departments of Oncology; Lombardi Comprehensive Cancer Center; Georgetown University Medical Center; Washington, DC USA ; Department of Radiation Medicine; Lombardi Comprehensive Cancer Center; Georgetown University Medical Center; Washington, DC USA.
JAKSTAT. 2012 Oct 1;1(4):274-84. doi: 10.4161/jkst.22313.
Most attempts to develop inhibitors of STAT transcription factors target either activating phosphorylation of tyrosine residue or SH2 domains. However, all six domains of STATs are highly conserved between the species and play important roles in the function of this family of transcription factors. STATs are involved in numerous protein-protein interactions that are likely to regulate and fine tune transcriptional activity. Targeting these interactions can provide plentiful opportunities for the discovery of novel drug candidates and powerful chemical biology tools. Using N-terminal domains as an example we describe alternative rational approaches to the development of modulators of JAK-STAT signaling.
大多数开发STAT转录因子抑制剂的尝试都针对酪氨酸残基的激活磷酸化或SH2结构域。然而，STATs的所有六个结构域在物种间高度保守，并且在这个转录因子家族的功能中发挥重要作用。STATs参与众多可能调节和微调转录活性的蛋白质-蛋白质相互作用。针对这些相互作用可为发现新型候选药物和强大的化学生物学工具提供大量机会。以N端结构域为例，我们描述了开发JAK-STAT信号调节剂的替代合理方法。
