TRIM44 Links UPS to Autophagy by Binding and Removing Misfolded Proteins

Abstract

Until recently, the ubiquitin — proteasome system (UPS) and autophagy were considered to be two independent systems that target proteins for degradation by proteasomes or via lysosomes, respectively. Here, we report that a member of the tripartite motif protein family 44 (TRIM44) is a novel link that connects the UPS system with the autophagy degradation pathway. Suppressing the UPS degradation pathway leads to TRIM44 upregulation, which further promotes aggregated protein clearance through the binding of K48 ubiquitin chains on proteins. TRIM44 expression activates autophagy, specifically enhancing the fusion of the autophagosome to the lysosome, which rapidly increases the rate of aggregate protein removal. Overall, our data reveal that TRIM44 is a newly identified link between the UPS system and the autophagy pathway. Delineating the cross-talk between these two degradation pathways may reveal new mechanisms of targeting aggregate-prone diseases, such as cancer and neurodegenerative disease.