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Int. J. Mol. Sci. 2017, 18(5), 923; doi:10.3390/ijms18050923

Regulation of G Protein-Coupled Receptors by Ubiquitination

1
Laboratory of GPCR Expression and Signal Transduction (L-GEST), Ghent University, Proeftuinstraat 86, 9000 Ghent, Belgium
2
Center for Medical Genetics Ghent; Ghent University, De Pintelaan 185, 9000 Ghent, Belgium
3
Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Medical Research Building 2, De Pintelaan 185, 9000 Ghent, Belgium
*
Author to whom correspondence should be addressed.
Academic Editor: Vsevolod V. Gurevich
Received: 6 February 2017 / Revised: 20 April 2017 / Accepted: 23 April 2017 / Published: 27 April 2017
(This article belongs to the Collection G Protein-Coupled Receptor Signaling and Regulation)
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Abstract

G protein-coupled receptors (GPCRs) comprise the largest family of membrane receptors that control many cellular processes and consequently often serve as drug targets. These receptors undergo a strict regulation by mechanisms such as internalization and desensitization, which are strongly influenced by posttranslational modifications. Ubiquitination is a posttranslational modification with a broad range of functions that is currently gaining increased appreciation as a regulator of GPCR activity. The role of ubiquitination in directing GPCRs for lysosomal degradation has already been well-established. Furthermore, this modification can also play a role in targeting membrane and endoplasmic reticulum-associated receptors to the proteasome. Most recently, ubiquitination was also shown to be involved in GPCR signaling. In this review, we present current knowledge on the molecular basis of GPCR regulation by ubiquitination, and highlight the importance of E3 ubiquitin ligases, deubiquitinating enzymes and β-arrestins. Finally, we discuss classical and newly-discovered functions of ubiquitination in controlling GPCR activity. View Full-Text
Keywords: G protein-coupled receptors (GPCR); ubiquitination; β-arrestin; deubiquitinating enzyme; E3 ubiquitin ligase G protein-coupled receptors (GPCR); ubiquitination; β-arrestin; deubiquitinating enzyme; E3 ubiquitin ligase
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Skieterska, K.; Rondou, P.; Van Craenenbroeck, K. Regulation of G Protein-Coupled Receptors by Ubiquitination. Int. J. Mol. Sci. 2017, 18, 923.

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