2014
DOI: 10.1128/mcb.00731-14
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The Ubiquitin Ligase RNF220 Enhances Canonical Wnt Signaling through USP7-Mediated Deubiquitination of β-Catenin

Abstract: Wnt/␤-catenin signaling plays critical roles in embryonic development and disease. Here, we identify RNF220, a RING domain E3 ubiquitin ligase, as a new regulator of ␤-catenin. RNF220 physically interacts with ␤-catenin, but instead of promoting its ubiquitination and proteasomal degradation, it stabilizes ␤-catenin and promotes canonical Wnt signaling. Our analysis showed that RNF220 interacts with USP7, a ubiquitin-specific peptidase, which is required for RNF220 to stabilize ␤-catenin. The RNF220/USP7 compl… Show more

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Cited by 85 publications
(82 citation statements)
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“…Thus, USP7 and Trip12 are mutual substrates for each other, and the balance between them would determine their effective levels to control their other target proteins, including those proteins involved in the DDR. We showed previously that USP7 interacts with RNF220, a RING domain ubiquitin ligase [16]. However, in that case, USP7 and RNF220 did not have a clear effect on each other's stability.…”
Section: Discussionmentioning
confidence: 79%
“…Thus, USP7 and Trip12 are mutual substrates for each other, and the balance between them would determine their effective levels to control their other target proteins, including those proteins involved in the DDR. We showed previously that USP7 interacts with RNF220, a RING domain ubiquitin ligase [16]. However, in that case, USP7 and RNF220 did not have a clear effect on each other's stability.…”
Section: Discussionmentioning
confidence: 79%
“…5C). Rnf220 is an E3 ubiquitin ligase with a RING finger domain that has been shown to stabilize b-catenin and, therefore, enhance canonical Wnt signaling (71). b-Catenin stabilization was shown to occur via deubiquitination by a complex of Rnf220 and the ubiquitinspecific protease 7 (71).…”
Section: Discussionmentioning
confidence: 99%
“…Rnf220 is an E3 ubiquitin ligase with a RING finger domain that has been shown to stabilize b-catenin and, therefore, enhance canonical Wnt signaling (71). b-Catenin stabilization was shown to occur via deubiquitination by a complex of Rnf220 and the ubiquitinspecific protease 7 (71). Promotion of Wnt/b-catenin signaling by canonical ligand, Wnt3a, and inhibition of Wnt antagonist, Dkk1, has been shown to decrease LPSinduced neutrophil influx and cytokine production (72).…”
Section: Discussionmentioning
confidence: 99%
“…11668019, Thermo Fisher Scientific). In Figure and , cells were transfected with siRNA for 48 h and further treated with P5091 for 48 h. In Figure , cells transfected with siRNAs were collected after 96 h. The sequences of the siRNA are as follows: siNOXA‐1 : GUAAUUAUUGACACAUUUC; siNOXA‐2: GGUGCACGUUUCAUCAAUUUG; siUSP7‐1: ACCCUUGGACAAUAUUCCU; siUSP7‐2: AGUCGUUCAGUCGUCGUAU; siUSP7‐3: UGACGUGUCUCUUGAUAAA; siATF4: GCCUAGGUCUCUUAGAUGA; siControl: UUCUCCGAACGUGUCACGU.…”
Section: Methodsmentioning
confidence: 99%