Fig. 8: Working model of the role of HERC2 as an autophagy regulator factor.
From: Autophagy dysregulation via the USP20-ULK1 axis in the HERC2-related neurodevelopmental disorder
In steady-state or basal autophagy, the ubiquitin ligase HERC2 interacts with and regulates USP20 protein levels by catalyzing its ubiquitylation-dependent proteasome degradation. In this context, the protein levels of ULK1, the autophagy initiating kinase, are controlled post-translationally by ubiquitylation-mediated protein degradation (left panel). Under conditions of activated autophagy by p38 activation, HERC2-USP20 interaction is disrupted. Subsequently, USP20 protein levels are upregulated. USP20 deubiquitylates ULK1, preventing its protein degradation and hence stabilizing its protein levels. This ultimately leads to a major activation of the autophagy pathway.
