title: Ubiquitination and the Regulation of Membrane Proteins.
abstract: Newly synthesized transmembrane proteins undergo a series of steps to ensure that only the required amount of correctly folded protein is localized to the membrane. The regulation of protein quality and its abundance at the membrane are often controlled by ubiquitination, a multistep enzymatic process that results in the attachment of ubiquitin, or chains of ubiquitin to the target protein. Protein ubiquitination acts as a signal for sorting, trafficking, and the removal of membrane proteins via endocytosis, a process through which multiple ubiquitin ligases are known to specifically regulate the functions of a number of ion channels, transporters, and signaling receptors. Endocytic removal of these proteins through ubiquitin-dependent endocytosis provides a way to rapidly downregulate the physiological outcomes, and defects in such controls are directly linked to human pathologies. Recent evidence suggests that ubiquitination is also involved in the shedding of membranes and associated proteins as extracellular vesicles, thereby not only controlling the cell surface levels of some membrane proteins, but also their potential transport to neighboring cells. In this review, we summarize the mechanisms and functions of ubiquitination of membrane proteins and provide specific examples of ubiquitin-dependent regulation of membrane proteins.
authors.affiliation: Centre for Cancer Biology, University of South Australia, Adelaide, Australia.
authors.forename: Natalie
authors.initials: N
authors.lastname: Foot
authors.affiliation: Centre for Cancer Biology, University of South Australia, Adelaide, Australia.
authors.forename: Tanya
authors.initials: T
authors.lastname: Henshall
authors.affiliation: Centre for Cancer Biology, University of South Australia, Adelaide, Australia.
authors.forename: Sharad
authors.initials: S
authors.lastname: Kumar
mesh_terms: D000818:Animals; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology*; D054875:Ubiquitination / Q000502:physiology*
chemical_list: D008565:Membrane Proteins