Provider: Ingenta Connect Database: Ingenta Connect Content: application/x-research-info-systems TY - ABST AU - Watanabe, Nobumoto AU - Osada, Hiroyuki TI - Phosphorylation-Dependent Protein-Protein Interaction Modules As Potential Molecular Targets for Cancer Therapy JO - Current Drug Targets PY - 2012-12-01T00:00:00/// VL - 13 IS - 13 SP - 1654 EP - 1658 KW - small-molecule inhibitors KW - Cancer Therapy KW - Molecular Targets KW - Plk1 KW - protein-protein interaction KW - Protein phosphorylation KW - purpurogallin KW - polo box domain KW - small molecule KW - high throughput screening N2 - Protein phosphorylation is a key event in signal transduction pathways. When upstream signals are stimulated, protein kinases are activated and phosphorylate their substrates, modulating their localization, conformation, and activity. In some cases, phosphorylated substrates become recognizable to other proteins—such interactions transduce and propel the signal onward. Certain domains specifically recognize phosphorylated residues of proteins, regulating cell growth and differentiation. Because the proteins that contain these domains also mediate diseases that are caused by dysregulated signal transduction, small molecules that inhibit such motifs are attractive candidates for the treatment of diseases, such as cancer. In this review, we summarize the domains that recognize phosphorylated proteins, particularly serine- and threonine-phosphorylated sequences in target proteins. In addition, we introduce a high-throughput screen that we developed to identify small-molecule inhibitors of phosphorylation-dependent protein-protein interactions. An example is presented, and the potential uses of this system are discussed. UR - https://www.ingentaconnect.com/content/ben/cdt/2012/00000013/00000013/art00010 M3 - doi:10.2174/138945012803530035 UR - https://doi.org/10.2174/138945012803530035 ER -