The small ubiquitin-like modifier (SUMO) modification, also called sumoylation, is a posttranslational modification of protein substrates, which is essential in cellular stress response. 2',3',4'-Trihydroxyflavone (2-D08) is a synthetic oxygenated flavonoid that inhibits sumoylation with an IC50 of 6 μM. The treatment of 2-D08 for 90 min in vitro inhibited the conjugation of SUMO-1, SUMO-2, and SUMO-3 to IκBα dose-dependently from 1 - 30 μM. The incubation of 30 μM 2-D08 for 6 hours inhibited the sumoylation of topoisomerase-I in BT-474 breast cancer cell lines. A significant overall inhibition of fibril formation was observed in the presence of 100μM 2-D08 at 48 hours. The incubation of 0.1 – 2 μM Aβ1 - 42Myc lymphoma cells 48 hour after the exposure, followed by rapid growth arrest and apoptotic cell death. When incubated with 75 μM 2-D08 for 24 hours, the fold change of the sub-G1 fraction in P493-6 lymphoma cells treated without tetracycline (Myc-off) were significantly lower than that in cells treated with tetracycline (Myc-on).
作用机制
2',3',4'-Trihydroxyflavone inhibits protein sumoylation by preventing transfer of SUMO from the UBC9-SUMO thioester to the substrate.
搜索
