Inhibition of protein SUMOylation by natural quinones.

Conjugation of small ubiquitin-related modifier (SUMO) to target proteins (SUMOylation) is a posttranslational modification that regulates a wide range of biological processes, including transcription, intracellular transport, DNA repair, DNA replication and cell signaling.1 SUMOylation is catalyzed by a multi-step enzymatic cascade that resembles ubiquitination: the process involves an E1-activating enzyme (a heterodimer consisting of Aos1 and Uba2), an E2-conjugating enzyme (Ubc9) and various E3 ligases.1 E3s catalyze SUMO conjugation to target proteins and may contribute to substrate specificity. SUMO is subsequently cleaved from target proteins by SUMO-specific isopeptidases. Because SUMO modifications have been implicated in a variety of disorders such as cancers2 and neurodegenerative diseases,3 the enzymes involved in SUMOylation are promising targets for therapeutic agents.