Abstract 21: Quantitative FRET technology for SUMOylation cascade and high-throughput screening assay for SUMOylation inhibitor in cancer drug discovery

The ubiquitin–proteasome system and ubiquitin-like protein pathways, such as SUMOylation, are critical in protein homeostasis and activities in vivo and are emerging as a new strategy to treat many acute and chronic human diseases, such as cancers. Although various kinase inhibitors have been developed as target-based therapy, solid tumors are still challenges in clinical therapy because various resistant are developed after kinase inhibitor treatments, and therapeutic agents with novel mechanisms are urgently needed. SUMO has been shown to modify various critical proteins, such as p53, MDM2, Estrogen receptor and androgen receptors. More recently, a genome-wide siRNA screening shown that inhibition of SUMO E1 ligases can lead to synergistically lethality of c-Myc overexpressed breast cancer cells. However, so far, specific inhibitor of SUMOylation is still not available for the community. Fig. 1. SUMOylation in human diseases and quantitative systems biology approach for basic and translational research of SUMOylation. We developed a novel quantitative Förster resonance energy transfer (FRET) technology platform for both basic kinetics parameter determinations and high-through screening(HTS) assays for SUMOylation cascade. The novel theoretical and experimental procedures for protein interactions affinity(Kd) determinations in the SUMOylation cascade, including the interaction between SUMO1 and its E2 ligase, Ubc9, E1 heterodimers(Aos1 and Uba2), E1 and E2 interactions(Ub...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Poster Presentations Source Type: research