Dual function of the Leon/USP5 deubiquitinase in the ubiquitin-proteasome and autophagic pathways

Dual function of the Leon/USP5 deubiquitinase in the ubiquitin-proteasome and autophagic pathways

Blog Article

The ubiquitin-proteasome system (UPS) and autophagy are highly conserved processes that maintain cellular health through the clearance of misfolded/aberrant proteins and damaged organelles.Ubiquitination is a crucial protein modification to lcpl chevrons regulate entry in these two pathways.However, the function of deubiquitinases (DUBs) in the UPS and autophagy remains largely unclear.The Leon/USP5 deubiquitinase is essential for maintaining ubiquitin homeostasis and proteasome function.

In our recent study, we found that Leon/USP5 depletion resulted in the induction of autophagosome formation and an enhancement of the autophagic flux.Additionally, a genetic analysis in Drosophila revealed that Leon overexpression suppressed Atg1-induced cell death.We further showed that Leon/USP5 interacts with the autophagy initiator Atg1/ULK1, regulating its levels and thus modulating autophagosome formation.These findings suggest that Leon/USP5 plays a dual role in regulation of UPS and autophagy.

Abbreviations: Atg1: autophagy-related 1; Atg7: autophagy-related 7; DUB: deubiquitinase; ED: enzyme dead; PTM: post-translational modification; SQSTM1: sequestosome 1; ULK1: unc-51 like autophagy activating kinase 1; whirlwind multi selector UPS: ubiquitin-proteasome system; USP5: ubiquitin-specific proteinase 5; WT: wild-type.