RT Journal Article
SR Electronic
T1 A conserved ubiquitin- and ESCRT-dependent pathway to regulate human lysosomal membrane proteins
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.11.18.389296
DO 10.1101/2020.11.18.389296
A1 Weichao Zhang
A1 Xi Yang
A1 Liang Chen
A1 Yun-Yu Liu
A1 Varsha Venkatarangan
A1 Lucas Reist
A1 Phyllis Hanson
A1 Haoxing Xu
A1 Yanzhuang Wang
A1 Ming Li
YR 2020
UL http://biorxiv.org/content/early/2020/11/20/2020.11.18.389296.abstract
AB The lysosome is an essential organelle to recycle cellular materials and maintain nutrient homeostasis, but the mechanism to down-regulate lysosomal membrane proteins is poorly understood. In this study, we developed a cycloheximide chase assay to measure the half-lives of ~30 human lysosomal membrane proteins, and identified RNF152 as a short-lived protein. The degradation of RNF152 depends on ubiquitin and the endosomal sorting complexes required for transport (ESCRT) machinery. Ubiquitinated RNF152 is sorted and internalized by the ESCRT machinery into the lysosomal lumen for degradation. Strikingly, when expressed in budding yeast, human RNF152 is also degraded by the vacuole (yeast lysosome) in an ESCRT-dependent manner. Thus, our study uncovered a conserved mechanism to down-regulate lysosome membrane proteins.Competing Interest StatementThe authors have declared no competing interest.