Cellular protein homeostasis is maintained by two major degradation pathways, namely the ubiquitin-proteasome system (UPS) and autophagy. Until recently, the UPS and autophagy were considered to be largely independent systems targeting proteins for degradation in the proteasome and lysosome, respectively. However, the identification of crucial roles of molecular players such as ubiquitin and p62 in both of these pathways as well as the observation that blocking the UPS affects autophagy flux and vice versa has generated interest in studying crosstalk between these pathways. Here, we critically review the current understanding of how the UPS and autophagy execute coordinated protein degradation at the molecular level, and shed light on our recent findings indicating an important role of an autophagy-associated transmembrane protein EI24 as a bridging molecule between the UPS and autophagy that functions by regulating the degradation of several E3 ligases with Really Interesting New Gene (RING)-domains.
Bibliographical noteFunding Information:
This work was supported by the National Research Foundation of Korea (NRF; grants 2015R1A2A1A01003845 and 2017R1A4A1015328) and “The Yonsei University Yonsei-SNU Collaborative Research Fund of 2017”.
© The Korean Society for Molecular and Cellular Biology. All rights reserved.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology