title: The role of ubiquitylation in receptor endocytosis and endosomal sorting.
abstract: Ligand-induced activation of transmembrane receptors activates intracellular signaling cascades that control vital cellular processes, such as cell proliferation, differentiation, migration and survival. Receptor signaling is modulated by several mechanisms to ensure that the correct biological outcome is achieved. One such mechanism, which negatively regulates receptor signaling, involves the modification of receptors with ubiquitin. This post-translational modification can promote receptor endocytosis and targets receptors for lysosomal degradation, thereby ensuring termination of receptor signaling. In this Commentary, we review the roles of ubiquitylation in receptor endocytosis and degradative endosomal sorting by drawing on the epidermal growth factor receptor (EGFR) as a well-studied example. Furthermore, we elaborate on the molecular basis of ubiquitin recognition along the endocytic pathway through compartment-specific ubiquitin-binding proteins and highlight how endocytic sorting machineries control these processes. In addition, we discuss the importance of ubiquitin-dependent receptor endocytosis for the maintenance of cellular homeostasis and in the prevention of diseases such as cancer.
authors.affiliation: Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Montebello, N-0310 Oslo, Norway. Kaisa.Haglund@rr-research.no
authors.forename: Kaisa
authors.initials: K
authors.lastname: Haglund
authors.forename: Ivan
authors.initials: I
authors.lastname: Dikic
mesh_terms: D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D025801:Ubiquitin; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases