Sumoylation (SUMO or small ubiquitin-like modifier) is a protein post-translational modification of proteins (e.g., p53, MDM2, STATs [signal transducer and activator of transcription], IƒÛB, and androgen and estrogen receptors) that are involved in many critical physiological processes, such as signal transduction, genome integrity, cell-cycle regulation, cell proliferation, and tumor genesis.

The phenomenon that Forster resonance energy transfer (FRET) occurs between two adjacent fluorophores with overlapping fluorescence spectrums has been used extensively in biological research to study protein interactions, intracellular signaling pathways, and discover novel bioactive chemicals for drug development. However, this technique has not been developed into high-throughput screening platform. Our lab is currently developing fluorescent protein-based FRET techniques to detect the interaction of different protein components of SUMOylation pathways in living cells. Using engineered fluorescent proteins to genetically tag protein components, we have established the interactions of SUMO1 with E2 and E3 ligases. We are also in the process of developing this FRET-based method into a high-throughput screening assay to discover small chemical inhibitors which can specifically disrupt protein-protein interactions involved in this network. The small chemical inhibitors will not only contribute to the investigation of SUMOylation and improve our knowledge about this important process, but the proposed work will also provide a novel approach for high-throughput screening assays targeting protein-protein interactions.

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