β-arrestin 2 oligomerization controls the Mdm2-dependent inhibition of p53

Boularan, Cédric; Scott, Mark G. H.; Bourougaa, Karima; Bellal, Myriam; Estève, Emmanuel; Thuret, Alain; Benmerah, Alexandre; Tramier, Marc; Coppey-Moisan, Maïté; Labbé-Jullié, Catherine; Fåhræus, Robin; Marullo, Stéfano

doi:10.1073/pnas.0705550104

Cited by 63 publications

(68 citation statements)

References 36 publications

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“…The N-domain in ␤-arrestin2 carries the binding site for E3 ligase Mdm2 (27,28), whereas USP33 binds both N and C domains. Mdm2-␤-arrestin binding occurs constitutively (29,30) and does not persist beyond 10-15 min of ␤ 2 AR activation (30).…”

Section: Discussionmentioning

confidence: 99%

β-Arrestin-dependent signaling and trafficking of 7-transmembrane receptors is reciprocally regulated by the deubiquitinase USP33 and the E3 ligase Mdm2

Shenoy¹,

Modi²,

Shukla

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

143

133

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␤-Arrestins are multifunctional adaptors that mediate the desensitization, internalization, and some signaling functions of seventransmembrane receptors (7TMRs). Agonist-stimulated ubiquitination of ␤-arrestin2 mediated by the E3 ubiquitin ligase Mdm2 is critical for rapid ␤2-adrenergic receptor (␤2AR) internalization. We now report the discovery that the deubiquitinating enzyme ubiquitin-specific protease 33 (USP33) binds ␤-arrestin2 and leads to the deubiquitination of ␤-arrestins. USP33 and Mdm2 function reciprocally and favor respectively the stability or lability of the receptor ␤-arrestin complex, thus regulating the longevity and subcellular localization of receptor signalosomes. Receptors such as the ␤2AR, previously shown to form loose complexes with ␤-arrestin (''class A'') promote a ␤-arrestin conformation conducive for binding to the deubiquitinase, whereas the vasopressin V2R, which forms tight ␤-arrestin complexes (''class B''), promotes a distinct ␤-arrestin conformation that favors dissociation of the enzyme. Thus, USP33-␤-arrestin interaction is a key regulatory step in 7TMR trafficking and signal transmission from the activated receptors to downstream effectors.endocytosis ͉ G protein-coupled receptors ͉ ubiquitination ͉ phosphorylation ͉ ERK1/2

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Section: Discussionmentioning

confidence: 99%

β-Arrestin-dependent signaling and trafficking of 7-transmembrane receptors is reciprocally regulated by the deubiquitinase USP33 and the E3 ligase Mdm2

Shenoy¹,

Modi²,

Shukla

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

143

133

View full text Add to dashboard Cite

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“…However, recent data localized these proteins to the plasma membrane (Lin et al, 2008), along the endocytic pathway (Becuwe et al, 2012b;O'Donnell et al, 2010;Patwari et al, 2009), or even in the nucleus (Boularan et al, 2007;Hara et al, 2011) during cargo recognition. Similar to b-arrestins, ARRDCs have been described to interact with clathrin and clathrin adaptors, suggesting that they could act on early endocytosis (Becuwe et al, 2012a;O'Donnell et al, 2010).…”

Section: Arrestins Are New Factors Involved In Mammalian Notch Degradmentioning

confidence: 99%

α-arrestin 1 (ARRDC1) and β-arrestins cooperate to mediate Notch degradation in mammals

Puca

Chastagner

Meas-Yedid

et al. 2013

Journal of Cell Science

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SummaryNotch signaling is a conserved signaling pathway implicated in embryogenesis and adult tissue maintenance. Notch signaling strength is strictly regulated, notably by maintaining a controlled pool of functional receptor at the cell surface. Mammalian non-activated Notch receptor is internalized, ubiquitylated by the Itch E3 ubiquitin ligase and degraded in the lysosomes. Here, we show that b-arrestins are necessary for Itch-Notch interaction and for Itch-driven ubiquitylation and degradation of Notch. Interestingly, b-arrestins do not directly bind Itch but heterodimerize with a member of another subfamily of arrestins called ARRDC1 or a-arrestin 1, which harbors PPxY motifs that allow direct interaction with Itch. Cells transfected with ARRDC1 mutated in PPxY motifs show reduced Itchmediated Notch ubiquitylation and impaired lysosomal degradation of Notch, as observed in b-arrestin 2/2 or Itch 2/2 cells. Our data show for the first time that ARRDC1 and b-arrestins heterodimerize and cooperate in the same complex to promote non-activated Notch receptor degradation, thus acting as negative regulators of Notch signaling.

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“…First, the ability to form oligomers might facilitate the interaction of b-arrestins with multiple substrates; alternatively, oligomers could represent an inactive pool of b-arrestins in the cytoplasm, as suggested by the heterodimerization between b-arrestins 1 and 2 that impairs the nuclear translocation of b-arrestin 1 (Storez et al, 2005). Impaired b-arrestin 2 oligomerization affects b2AR-dependent ERK activation without interfering with receptor internalization, suggesting that oligomers could also constitute an interface for the interaction with a distinct set of proteins (Boularan et al, 2007;Xu et al, 2008). However, these studies have not addressed the possible heterodimerization of a-with b-arrestins that has been hypothesized by Alvarez (Alvarez, 2008) and discussed in a review about the involvement of a-arrestins in the trafficking of yeast membrane transporters (Polo and Di Fiore, 2008).…”

Section: Arrestin Homo-and Hetero-associationsmentioning

confidence: 99%

α-Arrestins – new players in Notch and GPCR signaling pathways in mammals

Puca

Brou

2014

Journal of Cell Science

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For many years, b-arrestins have been known to be involved in G-protein-coupled receptor (GPCR) desensitization. However, barrestins belong to a family of proteins that act as multifunctional scaffolding proteins, in particular during trafficking of transmembrane receptors. The arrestin family comprises visual arrestins, b-arrestins and a-arrestins. In mammals, the functions of the a-arrestins are beginning to be elucidated, and they are described as versatile adaptors that link GPCRs or the Notch receptor to E3 ubiquitin ligases and endocytic factors. These aarrestins can act in sequence, complementarily or cooperatively with b-arrestins in trafficking and ubiquitylation events. This Commentary will summarize the recent advances in our understanding of the functions and properties of these a-arrestin proteins in comparison to b-arrestins, and will highlight a new hypothesis linking their functional complementarity to their physical interactions. a-and b-arrestins could form transient and versatile heterodimers that form a bridge between cargo and E3 ubiquitin ligases, thus allowing trafficking to proceed.

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β-arrestin 2 oligomerization controls the Mdm2-dependent inhibition of p53

Cited by 63 publications

References 36 publications

β-Arrestin-dependent signaling and trafficking of 7-transmembrane receptors is reciprocally regulated by the deubiquitinase USP33 and the E3 ligase Mdm2

β-Arrestin-dependent signaling and trafficking of 7-transmembrane receptors is reciprocally regulated by the deubiquitinase USP33 and the E3 ligase Mdm2

α-arrestin 1 (ARRDC1) and β-arrestins cooperate to mediate Notch degradation in mammals

α-Arrestins – new players in Notch and GPCR signaling pathways in mammals

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