title: Minireview: ubiquitination-regulated G protein-coupled receptor signaling and trafficking.
abstract: G protein-coupled receptors (GPCRs) are the largest and most diverse superfamily of membrane proteins and mediate most cellular responses to hormones and neurotransmitters. Posttranslational modifications are considered the main regulators of all GPCRs. In addition to phosphorylation, glycosylation, and palmitoylation, increasing evidence as reviewed here reveals that ubiquitination also regulates the magnitude and temporospatial aspects of GPCR signaling. Posttranslational protein modification by ubiquitin is a key molecular mechanism governing proteins degradation. Ubiquitination mediates the covalent conjugation of ubiquitin, a highly conserved polypeptide of 76 amino acids, to protein substrates. This process is catalyzed by 3 enzymes acting in tandem: an E1, ubiquitin-activating enzyme; an E2, ubiquitin-carrying enzyme; and an E3, ubiquitin ligase. Ubiquitination is counteracted by deubiquitinating enzymes that deconjugate ubiquitin-modified proteins and rescue the substrate from proteasomal degradation. Although ubiquitination is known to target many GPCRs for lysosomal or proteasomal degradation, emerging findings define novel roles for the basal status of ubiquitination and for rapid deubiquitination and transubiquitination controlling cell surface expression and cellular responsiveness of some GPCRs. In this review, we highlight the classical and novel roles of ubiquitin in the regulation of GPCR function, signaling, and trafficking.
authors.affiliation: Institute of Applied Molecular Medicine, San Pablo-CEU University School of Medicine, Madrid, 28668, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Alonso
authors.forename: Peter A
authors.initials: PA
authors.lastname: Friedman
mesh_terms: D000818:Animals; D004194:Disease; D006801:Humans; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D054875:Ubiquitination
chemical_list: D043562:Receptors, G-Protein-Coupled