Project description:To investigate the mechanism of anti-fibrotic effect of ginkgetin, we performed gene expression profiling analysis using data obtain from RNA-seq of LX2 cells.
Project description:The LX2 cells were subjected to 50mM ethanol stimulus with or without STING inhibitor IFM-004490-7 10μM (STINGX) pretreatment. We then performed gene expression profiling analysis using data obtained from RNA-seq of 3 different groups (Control, ETOH, ETOH-STX, STX)
Project description:D-site binding protein, DBP, is a clock-controlled transcription factor and drives daily rhythms of physiological processes through the regulation of an array of genes harboring a DNA binding motif, D-box. DBP protein levels show a circadian oscillation with an extremely robust peak/trough ratio, but how the temporal pattern is regulated by post-translational regulation is unclear. In this study, we found that DBP protein levels are down-regulated by the ubiquitin-proteasome pathway. We screened 19 dominant-negative forms of E2 enzymes and found that UBE2G1 and UBE2T mediate the degradation of DBP. A proteomic analysis of DBP-interacting proteins and database screening identified Tumor necrosis factor Receptor-Associated Factor 7 (TRAF7), a RING-type E3 ligase, that forms a complex with UBE2G1 and/or UBE2T. Overexpression of TRAF7 down-regulated DBP protein level, while knockdown of TRAF7 up-regulated DBP in cultured cells. Knockout of TRAF7 in NIH3T3 cells revealed that TRAF7 mediates the time-of-the-day-dependent regulation of DBP levels. Furthermore, TRAF7 has a period-shortening effect on the cellular clock. Together, TRAF7 plays an important role in circadian clock oscillation through destabilization of DBP.
