Figure 8. Model for ubiquitin flux through the endocytic pathway, illustrating how phosphorylation of ubiquitin at Ser57 can alter ubiquitin metabolism by limiting recycling of ubiquitin and promoting its delivery to the vacuole for degradation.

(I) Plasma membrane proteins can be conjugated to ubiquitin, resulting in sorting and internalization by endocytosis (II). Ubiquitinated cargos on the limiting membrane of the endosome can be deubiquitylated (III) resulting in recycling of both cargo and ubiquitin, or they can be captured and sorted by ESCRT machinery into vesicles that bud into the lumen of the endosome. (IV) In the final stages of the ESCRT pathway, ubiquitin can be recycled prior packaging of cargo into vesicles by Doa4, but this mode of ubiquitin recycling is abrogated by phosphorylation at the Ser57 position of ubiquitin (inset).