title: Chapter Nine - Cellular Roles of Beta-Arrestins as Substrates and Adaptors of Ubiquitination and Deubiquitination.
abstract: β-Arrestin1 and β-arrestin2 are homologous adaptor proteins that are ubiquitously expressed in mammalian cells. They belong to a four-member family of arrestins that regulate the vast family of seven-transmembrane receptors that couple to heterotrimeric G proteins (7TMRs or GPCRs), and that modulate 7TMR signal transduction. β-Arrestins were originally identified in the context of signal inhibition via the 7TMRs because they competed with and thereby blocked G protein coupling to 7TMRs. Currently, in addition to their role as desensitizers of signaling, β-arrestins are appreciated as multifunctional adaptors that mediate trafficking and signal transduction of not only 7TMRs, but a growing list of additional receptors, ion channels, and nonreceptor proteins. β-Arrestins' interactions with their multifarious partners are based on their dynamic conformational states rather than particular domain-domain interactions. β-Arrestins adopt activated conformations upon 7TMR association. In addition, β-arrestins undergo various posttranslational modifications that are choreographed by activated 7TMRs, including phosphorylation, ubiquitination, acetylation, nitrosylation, and SUMOylation. Ubiquitination of β-arrestins is critical for their high-affinity interaction with 7TMRs as well as with endocytic adaptor proteins and signaling kinases. β-Arrestins also function as critical adaptors for ubiquitination and deubiquitination of various cellular proteins, and thereby affect the longevity of signal transducers and the intensity of signal transmission.
authors.affiliation: Department of Medicine (Cardiology), Duke University Medical Center, Durham, North Carolina, United States.
authors.forename: P-Y
authors.initials: PY
authors.lastname: Jean-Charles
authors.affiliation: Department of Medicine (Cardiology), Duke University Medical Center, Durham, North Carolina, United States; Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, United States.
authors.forename: N J
authors.initials: NJ
authors.lastname: Freedman
authors.affiliation: Department of Medicine (Cardiology), Duke University Medical Center, Durham, North Carolina, United States; Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, United States. Electronic address: skshenoy@dm.duke.edu.
authors.forename: S K
authors.initials: SK
authors.lastname: Shenoy
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002477:Cells / Q000378:metabolism*; D006801:Humans; D013379:Substrate Specificity; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination; D000071557:beta-Arrestins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000071557:beta-Arrestins; D044767:Ubiquitin-Protein Ligases
keywords: GPCR; Mdm2; USP20; endocytosis; ubiquitin; β-arrestin