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P14_3_3 binds USP8. 59 / 60
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"The somatic variations in our study are in the catalytic conserved domain of USP8 protein and lead to disruption of the interaction between USP8 catalytic domain and 14-3-3 protein (Fig.  xref )."
38862897
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"For example, the Ser680 residue of USP8 is phosphorylated during the interphase stage of cell division, which enables USP8 to bind to the 14-3-3 protein."
36142702
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"These mutations inhibited 14-3-3 protein binding to USP8 and resulted in a higher deubiquitinating enzyme (DUB) activation."
27569239
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"USP8 may undergo a conformational change from an active state to an inhibitory state based on the structure of the 14-3-3 protein that binds to phosphorylated USP8 [ xref ]."
36142702
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"Thus, these changes impair interactions between USP8 and 14-3-3 proteins, which normally suppress deubiquitinase activity [ xref ]."
33498176
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"These mutations impair the interaction between 14-3-3 and USP8 and enhance its cleavage by a specific protease, thus increasing USP8 deubiquitylation activity."
35954322
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"Phosphorylation of S680 in the vertebrate conserved amino acid sequence RSYSSP in Usp8 leads to binding of 14–3–3 proteins to Usp8 [34–38] ."
23333852
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"Indeed, our data demonstrate that Usp8 binds to 14–3–3 proteins in a phosphorylated S680-dependent manner ( Fig. 9 )."
23333852
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"USP8 mutations disrupt the interaction between USP8 and the 14-3-3 protein, thereby allowing USP8 cleavage and increased enzymatic activity ( xref ); this protects EGFR from lysosomal degradation, which leads to increased expression of EGFR ( xref ) ( xref ) and pro-opiomelanocortin ( POMC) ( xref , xref )."
32201880
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"To address the functionality of S680 phosphorylation, we tested whether binding of 14–3–3 proteins to Usp8 depends on phosphorylation of S680."
23333852
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"Pro720Arg—these mutations abrogate 14-3-3 protein binding to USP8 entirely, and this loss of interaction constitutively enhances the deubiquitinating enzyme activity of mutant USP8 [ xref ]."
41331709
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"It has been postulated that 14-3-3 binding to USP8 may result in: alterations in its enzymatic activity, changes in subcellular localisation or 14-3-3 may in fact mediate the binding of other proteins[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
28923280
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"Furthermore, the Usp8 mutant S680A was not able to interact with GST14–3–3 proteins ( Fig. 9 C and F), showing that phosphorylated S680 is responsible for binding of Usp8 to 14–3–3 proteins."
23333852
sparser
"Another way is that phosphorylation recruits a partner to bind with DUBs, such as USP8, which enables USP8 to interact with 14-3-3 proteins, thereby inhibiting its activity [ xref ]."
36142702
sparser
"Mutations reduced the interaction between USP8 and 14-3-3 and enhanced USP8 activity."
25942478
sparser
"Catalytically inactive Usp8 also efficiently interacted with 14–3–3, showing that the deubiquitinating activity of Usp8 is not necessary for binding of Usp8 to 14–3–3 proteins ( Fig. 9 C and F)."
23333852
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"The interaction between USP8 and 14-3-3 proteins is characterized by dynamic behavior, in which binding and dissociation occur depending on the phosphorylation state of USP8."
39684405
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"The mutations in this region can disrupt the binding of 14-3-3 protein to USP8, thereby relieving the inhibition on the deubiquitinating enzyme activity of USP8."
41331709
sparser
"We therefore examined whether Arg 677 , Ser 678 , Ser 680 , and Pro 682 are required for the 14-3-3 binding of UBPY."
17720156
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"Whereas UBPY S680A completely lost the binding ability, UBPY S678A bound to 14-3-3s as efficiently as the wild-type protein ( Fig. 1 B)."
17720156
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"Our experiment showed that Usp8 Y679F binds to GST14–3–3 with the same affinity as Usp8 WT and Usp8 C748, while binding of Usp8 S680A to 14–3–3 was largely abolished ( Fig. 10 A and C )."
23333852
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"1 B and C indicated that the 14-3-3-binding motif around Ser 680 is required for the 14-3-3 binding of UBPY."
17720156
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"These results show that phosphorylation of Y679 does not affect binding of 14–3–3 to Usp8."
23333852
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"We next examined whether the 14-3-3 binding to UBPY requires the phosphorylation of UBPY."
17720156
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"It has previously been reported that mutation of S680 results in enhanced Usp8 activity towards EGFR, although EGF stimulation did not affect the level of S680 phosphorylation and 14–3–3 binding of Us[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
23333852
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"14-3-3 binds to USP8 in a phosphorylation-dependent manner and inhibits its catalytic activity ."
25721765
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"Stimulation of cells with EGF does not change the levels of S680 phosphorylation and 14–3–3 binding of Usp8 [35] ."
23333852
sparser
"Overall, these results show that 14–3–3 proteins bind to Usp8 in a pS680-dependent manner and that mutation of Y679 in the binding motif does not affect 14–3–3 binding."
23333852
sparser
"These results indicated that 14-3-3 proteins bind to the 14-3-3-binding motif around Ser 680 of UBPY when Ser 680 is phosphorylated."
17720156
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"To understand the significance of the UBPY–14-3-3 interaction, we first examined whether the subcellular localization of UBPY is regulated by 14-3-3s."
17720156
sparser
"Our results are consistent with previously published results that phosphorylation of S680 in amino acid sequence RSYSSP in Usp8 leads to binding of 14–3–3 proteins to Usp8 [34–38] ."
23333852
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"By contrast, GST-14-3-3ε did not inhibit the activity of UBPY S680A which does not interact with 14-3-3s ( Fig. 4 B, top)."
17720156
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"On the other hand, several Usp8 serine phosphorylation sites were identified using MS analysis.To address the functionality of S680 phosphorylation, we tested whether binding of 14-3-3 proteins to Usp[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
23333852
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"14-3-3 binds to USP8 in a phosphorylation dependent manner and inhibits its catalytic activity [33]."
25721765
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"The CD-associated variants lead to the loss of the 14-3-3 interaction and cleavage of USP8 just upstream of the interacting site, resulting in a C-terminal 40 kDa protein fragment with an enhanced DUB activity [ xref ]."
38067388
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"Using a GST14-3-3 pull-down experiment, we demonstrate here that Usp8 WT and Usp8 640-1080 interact with 14-3-3 proteins."
23333852
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"Furthermore, the Usp8 mutant S680A was not able to interact with GST14-3-3 proteins, showing that phosphorylated S680 is responsible for binding of Usp8 to 14-3-3 proteins."
23333852
sparser
"These mutations aggregate within the 14-3-3 binding motif of USP8 and disrupt the interaction between USP8 and 14-3-3 protein, resulting in an elevated capacity to protect EGFR from lysosomal degradation."
25675982
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"In contrast, MS analysis did result in the identification of several serine phosphorylation sites, including the S680 14–3–3 binding site, and subsequent experiments showed that this site is responsib[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
23333852
sparser
"Immunoblotting of the precipitates with anti-phospho-14-3-3-binding motif and anti-14-3-3 antibodies, however, showed that the levels of Ser 680 phosphorylation and UBPY–14-3-3 interaction are unchan[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
17720156
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"We next examined the interaction between UBPY and 14-3-3s in the M phase by co-immunoprecipitation."
17720156
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"In addition, phosphatase treatment of UBPY, as well as the addition of an excess of the Ser 680 -phosphorylated, but not non-phosphorylated, peptide corresponding to the surrounding 14-3-3-binding seq[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
17720156
sparser
"Together, these results indicate that UBPY binds to 14-3-3 proteins via the consensus binding motif around Ser 680 and the binding is regulated by Ser 680 phosphorylation."
17720156
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"By contrast, it did not inhibit the activity of UBPY S680A which does not associate with 14-3-3s ( Fig. 4 )."
17720156
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"Overall, these results show that 14-3-3 proteins bind to Usp8 in a pS680 dependent manner and that mutation of Y679 in the binding motif does not affect 14-3-3 binding."
23333852
reach
"These mutations inhibited 14-3-3 protein binding to USP8 and resulted in a higher deubiquitinating enzyme (DUB) activation."
27569239
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"Our results are consistent with previously published results that phosphorylation of S680 in amino acid sequence RSYSSP in Usp8 leads to binding of 14-3-3 proteins to Usp8 [34-38]."
23333852
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"Therefore, the binding of 14-3-3s to UBPY is possibly a common regulatory mechanism acquired in higher eukaryotes."
17720156
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"Phosphorylation of S680 in the vertebrate conserved amino acid sequence RSYSSP in Usp8 leads to binding of 14-3-3 proteins to Usp8 [34-38]."
23333852
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"Indeed, our data demonstrate that Usp8 binds to 14-3-3 proteins in a phosphorylated S680 dependent manner."
23333852
sparser
"In the interphase stage of cell division, the Ser680 residue of USP8 is phosphorylated, which enables USP8 to bind to the 14-3-3 protein This binding in turn inhibits the catalytic activity of USP8 ( xref ) ( xref )."
34177595
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"Finally, when the 14-3-3 BM of USP8 RSY*SSP (*S, S718 in humans and S680 in mice) binds to 14-3-3 protein, then it's being phosphorylated and suppress the USP8 catalytic activity [ 6 ]."
33600786
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"Together, these results indicate that UBPY binds to 14-3-3 proteins via the consensus binding motif around Ser 680 and the binding is regulated by Ser 680 phosphorylation.Previous studies have shown t[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
17720156
sparser
"The USP8-14-3-3 interaction was also confirmed in three other studies: one used tandem affinity purification (TAP) coupled with multidimensional protein identification technology [ xref ]; another used 14-3-3 affinity chromatography with HeLa cell extracts and found that the USP8-14-3-3 interaction appears to occur in a cell-cycle dependent manner [ xref ]; 14-3-3 epsilon, gamma, and zeta were identified as USP8-binding proteins using co-immunoprecipitation followed by mass spectrometric analysis [ xref ]."
18687060
sparser
"It is plausible that after the 14-3-3 protein allosterically binds to phosphorylated USP8; USP8 undergoes a conformational change from an active state to an inhibitory state ( xref )."
34177595
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"Catalytically inactive Usp8 also efficiently interacted with 14-3-3, showing that the deubiquitinating activity of Usp8 is not necessary for binding of Usp8 to 14-3-3 proteins."
23333852
sparser
"USP8 mutations impair interactions between USP8 and 14-3-3 proteins which normally suppress deubiquitinase activity [ xref ]."
36428684
sparser
"Surprisingly, when analyzing the impact of P720R and S718del USP8 mutations on USP8 interaction with 14-3-3 proteins, we observed that P720R USP8 mutant was still capable to bind to 14-3-3 proteins, being this data in agreement with results obtained by means of fluorescence polarization assay by the group of Ottmann [ xref ]."
35626057
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"Moreover, these findings offer valuable insights into the crucial USP8-14-3-3 interaction and might provide a starting point for future structure-based drug discovery studies on its modulation with the aim of targeting and stabilizing this PPI interface as a novel potential therapeutic strategy for CD."
35626057