Abstract
Autophagy is a major degradation pathway that utilizes lysosome hydrolases to degrade cellular constituents and is often induced under cellular stress conditions to restore cell homeostasis. Another prime degradation pathway in the cells is ubiquitin-proteasome system (UPS), in which proteins tagged by certain types of polyubiquitin chains are selectively recognized and removed by proteasome. Although the two degradation pathways are operated independently with different sets of players, recent studies have revealed reciprocal cross talks between UPS and autophagy at multiple layers. In this review, we summarize the roles of protein ubiquitination and deubiquitination in controlling the initiation, execution, and termination of bulk autophagy as well as the role of ubiquitination in signaling certain types of selective autophagy. We also highlight how dysregulation of ubiquitin-mediated autophagy pathways is associated with a number of human diseases and the potential of targeting these pathways for disease intervention.
Highlights
Ubiquitin-proteasome system (UPS) and autophagy are two major cellular degradation machineries in eukaryotes, both of which are crucial in eliminating misfolded/ unfolded proteins to maintain cell and tissue homeostasis and to prevent aging-related changes and a plethora of human diseases
CRISPR-mediated knockout analysis on HeLa cells revealed that OPTN, NDP52 and TAX1BP1 are redundantly required for Besides Parkin, mitophagy can be regulated by other factors that influence on the ubiquitination of mitochondrial membrane proteins
In this review, we discussed the impact of protein ubiquitination in autophagy regulation
Summary
Ubiquitin-proteasome system (UPS) and autophagy are two major cellular degradation machineries in eukaryotes, both of which are crucial in eliminating misfolded/ unfolded proteins to maintain cell and tissue homeostasis and to prevent aging-related changes and a plethora of human diseases. Beclin-1 K63 ubiquitination is mediated by Cul4 E3 ligase with AMBRA1 as a substrate adaptor, thereby promoting autophagy [29]. In contrast to TRAF6 and AMBRA1, the ubiquitin ligases NEDD4 and RNF216 promote Beclin-1 proteasomal degradation to inhibit autophagy by assembling K11- and K48-linked ubiquitin chains on Beclin-1, respectively [31, 32].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
