E3 ubiquitin ligases as regulators of membrane protein trafficking and degradation.
Ubiquitination is a regulated post-translational modification that conjugates ubiquitin (Ub) to lysine residues of target proteins and determines their intracellular fate. The canonical role of ubiquitination is to mediate degradation by the proteasome of short-lived cytoplasmic proteins that carry a single, polymeric chain of Ub on a specific lysine residue. However, protein modification by Ub has much broader and diverse functions involved in a myriad of cellular processes. Monoubiquitination, at one or multiple lysine residues of transmembrane proteins, influences their stability, protein-protein recognition, activity and intracellular localization. In these processes, Ub functions as an internalization signal that sends the modified substrate to the endocytic/sorting compartments, followed by recycling to the plasma membrane or degradation in the lysosome. E3 ligases play a pivotal role in ubiquitination, because they recognize the acceptor protein and hence dictate the high specificity of the reaction. The multitude of E3s present in nature suggests their nonredundant mode of action and the need for their controlled regulation. Here we give a short account of E3 ligases that specifically modify and regulate membrane proteins. We emphasize the intricate network of interacting proteins that contribute to the substrate-E3 recognition and determine the substrate's cellular fate.
d'Azzo
Alessandra
A
Department of Genetics and Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, TN, USA. alessandra.dazzo@stjude.org
Bongiovanni
Antonella
A
Nastasi
Tommaso
T
D022005:Adherens Junctions / Q000502:physiology; D000818:Animals; D019070:Cell Lineage; D002462:Cell Membrane / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004705:Endocytosis; D005656:Fungal Proteins / Q000378:metabolism; D017629:Gap Junctions / Q000502:physiology; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008954:Models, Biological; D000075687:NEDD8 Protein; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding; D021381:Protein Transport; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000502:physiology*; D014452:Ubiquitins / Q000378:metabolism
D005656:Fungal Proteins; D000075687:NEDD8 Protein; C082860:NEDD8 protein, human; D025801:Ubiquitin; D014452:Ubiquitins; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex