Impairment of proteasome-associated deubiquitinating enzyme Uchl5/UBH-4 affects autophagy.

ABSTRACT: The autophagy-lysosomal pathway (ALP) and the ubiquitin-proteasome system (UPS) are the two major intracellular proteolytic systems that mediate protein turnover in eukaryotes. Although a crosstalk exists between these two systems, it is still unclear how UPS and ALP interact in vivo. Here, we investigated how impaired function of the proteasome-associated deubiquitinating enzyme (DUB) Uchl5/UBH-4 affects autophagy in human cells and in a multicellular organism. We show that downregulation of Uchl5 by siRNA reduces autophagy by partially blocking the fusion of autophagosomes with the lysosomes in HeLa cells, which is similar to a previously reported role of the proteasome-associated DUB Usp14 on autophagy. However, exposure of Caenorhabditis elegans to ubh-4 or usp-14 RNAi, or to their pha

SUBMITTER: Jha S 

PROVIDER: S-EPMC11832120 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature