Chapter Nine - Cellular Roles of Beta-Arrestins as Substrates and Adaptors of Ubiquitination and Deubiquitination.

Published

Journal Article (Review)

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.

Full Text

Duke Authors

Cited Authors

  • Jean-Charles, P-Y; Freedman, NJ; Shenoy, SK

Published Date

  • January 2016

Published In

Volume / Issue

  • 141 /

Start / End Page

  • 339 - 369

PubMed ID

  • 27378762

Pubmed Central ID

  • 27378762

Electronic International Standard Serial Number (EISSN)

  • 1878-0814

International Standard Serial Number (ISSN)

  • 1877-1173

Digital Object Identifier (DOI)

  • 10.1016/bs.pmbts.2016.04.003

Language

  • eng