title: Regulation of endocytic sorting by ESCRT-DUB-mediated deubiquitination.
abstract: Endocytosis of cell surface receptors mediates cellular homeostasis by coordinating receptor distribution with downstream signal transduction and attenuation. Post-translational modification with ubiquitin of these receptors, as well as the proteins that comprise the endocytic machinery, modulates cargo progression along the endocytic pathway. The interplay between ubiquitination states of cargo and sorting proteins drives trafficking outcomes by directing endocytosed material toward either lysosomal degradation or recycling. Deubiquitination by specific proteinases creates a reversible system that promotes spatial and temporal organization of endosomal sorting complexes required for transport (ESCRTs) and supports regulated cargo trafficking. Two dubiquitinating enzymes--ubiquitin-specific protease 8 (USP8/Ubpy) and associated molecule with the SH3 domain of STAM (AMSH)--interact with ESCRT components to modulate the ubiquitination status of receptors and relevant sorting proteins. In doing so, these ESCRT-DUBs control receptor fate and sorting complex function through a variety of mechanisms described herein.
authors: Ben May Department for Cancer Research, The University of Chicago, Chicago, IL 60637, USA.
authors: Michelle H
authors: MH
authors: Wright
authors: Ilana
authors: I
authors: Berlin
authors: Piers D
authors: PD
authors: Nash
mesh_terms: D004705:Endocytosis; D010450:Endopeptidases / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D011485:Protein Binding; D021381:Protein Transport; D011956:Receptors, Cell Surface / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D011956:Receptors, Cell Surface; C486696:STAMBP protein, human; D010450:Endopeptidases; C541534:USP8 protein, human; D043222:Ubiquitin Thiolesterase