The anti-apoptotic ubiquitin conjugating enzyme BIRC6/BRUCE regulates autophagosome-lysosome fusion

摘要: The Inhibitor of Apoptosis (IAP) family member, Baculoviral IAP Repeat Containing 6 (BIRC6)/BRUCE is a ubiquitin conjugating E2 enzyme and well-established anti-apoptosis regulator. However, its role in mammalian autophagy has not been shown. We identified BIRC6 as an important positive regulator macroautophagy/autophagy by performing siRNA screen targeting enzymes the pathway. Compared to wild-type cells, BIRC6-deficient cells show accumulation lipidated LC3B both at basal starved conditions. Furthermore, deficiency blocks starvation-induced autophagic flux monitored tandem fluorescent sensor, mCherry-GFP-LC3B. Most strikingly, fusion autophagosomes lysosomes blocked cells. colocalizes with lysosomal protein LAMP2 biochemically interacts STX17 (syntaxin 17), which marker for completed autophagosomes. These data collectively suggest that bridges interacting these proteins. Because deletion mutant lacking UBC domain partially rescues autophagosome-lysosome defect this event independent catalytic activity.