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

Prog Mol Biol Transl Sci. 2016:141:339-69. doi: 10.1016/bs.pmbts.2016.04.003. Epub 2016 May 7.


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.

Keywords: GPCR; Mdm2; USP20; endocytosis; ubiquitin; β-arrestin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cells / metabolism*
  • Humans
  • Substrate Specificity
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination*
  • beta-Arrestins / metabolism*


  • Adaptor Proteins, Signal Transducing
  • beta-Arrestins
  • Ubiquitin-Protein Ligases