Molecular mechanism of ubiquitin-dependent traffic

Posttranslational modification (PTM) of signaling receptors by the covalent attachment of one, or often more, ubiquitin (Ub) moieties has emerged as the major regulatory mechanism responsible for receptor “downregulation.” Pioneering work in yeast has demonstrated that Ub is required for the first step in cargo internalization as well as for targeting cargos to vacuoles (the yeast equivalent of lysosomes) [1, 2]. Following these initial observations, there are now numerous reports of ubiquitination of a vast array of mammalian signaling receptors, such as RTKs, GPCRs, MHC-I, NOTCH, various channels and transporters, cytokine, and interferon receptors (reviewed in [3–8]). The molecular basis of Ub-dependent regulation of receptor endocytosis is being clarified. In this chapter, we will give a general overview of the mammalian system.