The SUMOylation Of RhoB Regulates The Autophagy Induced By DNA Damage

Autophagy is a catabolic process that involves the degradation of cytoplasmic components,protein aggregates and organelles through the formation of autophagosomes,which are degraded by fusion with lysosomes.However,autophagy is rapidly upregulated under adverse conditions,including nutrient deprivation,hypoxia,radiation and anticancer drugs,to recycle energy and supply macromolecules for biosynthesis,leading to the cells adapting to the stress.Although autophagy is primary to contribute to cell survival,in certain conditions,it can lead to cell death but the mechanisms have not been fully clarified.RhoB is a member of small GTPases from the Rho family,participates in numerous essential cellular processes,including actin cytoskeleton arrangements,cell migration,protein traffic and inflammation.Mechanistic studies show that RhoB levels are found decreased in various types of cancer;suggesting a tumor suppressor role of RhoB.Consistent with its suppressing role,RhoB is also an important effecter in DNA damage induced apoptosis.However,the research about regulations of RhoB is little and the molecular mechanisms about the function of RhoB during the apoptosis induced by DNA damage are largely unknown.In this study,we found that RhoB interacts with Ubc9 and can be sumoylated which is enhanced by SUMO E3 ligase PIAS1.The sumoylated RhoB can change its location after DNA damge which is critical for translocation TSC complex to lysosomes to inhibit mTORCl and subsequent initiation of robust autophagy.