IndraLab

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USP20 binds HERC2. 40 / 48
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"Moreover, we show that p38 acts as a modulator of this pathway, since p38 activation disrupts HERC2-USP20 interaction, leading to increased USP20 and LC3-II protein levels."
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"In unstressed cells, HERC2 binds USP20 to maintain a low basal level of USP20 in cells."
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"The results confirmed the interaction between HERC2 and USP20 proteins."
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"Then, we hypothesized that p38 activity might modulate the interaction between HERC2 and USP20."
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"After 3 and 6 h of stimulation with H 2 O 2 , the levels of USP20 interacting with HERC2 were reduced (Fig. xref , low exposition), while the amount of pulled-down HERC2 remained unchanged (Fig. xref )."
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"Consistent with this, we found that HERC2 binds the catalytic domain (aa 145-686) of USP20, which includes all four phosphorylation sites."
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"HERC2-USP20 interaction was greatly reduced when p38 phosphorylation was induced by MKK6 overexpression (Fig. xref )."
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"Protein interaction of HERC2 with USP20 is regulated by p38 activation."
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"Chk1 activation is indirectly regulated via modulation of Claspin stability by ubiquitination and deubiquitination events, involving the HERC2 and USP20 complex [49,50]."
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"To delve deeper into the molecular mechanisms underpinning HERC2-dependent autophagy regulation, we sought to determine whether HERC2 and USP20 proteins interact."
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"These findings provided further support for the notion that p38 activation disrupts the HERC2-USP20 interaction, a mechanism that could potentially contribute to the stabilization of USP20."
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"We found that the presence of USP20 in the HERC2 immunocomplex decreased upon HU treatment (Figure xref ), so did the presence of HERC2 in the FALG-USP20 immunocomplex, whereas the interaction between USP20(4SA) and HERC2 did not decrease in response to HU treatment (Figure xref )."
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"In basal or steady-state autophagy conditions (Fig. xref , left panel), HERC2 interacts with USP20, potentially promoting its polyubiquitylation and subsequent proteasomal degradation."
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"Mechanistically, we corroborate an interaction between HERC2 and the deubiquitylating enzyme USP20; and demonstrate that HERC2 deficiency leads to increased USP20 protein levels."
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"We confirmed the interaction between USP20 and HERC2 by endogenous Co-IP (Figure xref and xref )."
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"Then, we hypothesized that p38 activity might modulate the interaction between HERC2 and USP20."
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"However, whether p38 can regulate autophagy through directly targeting USP20 has not yet been explored.Our study unveils that p38 activation leads to the disruption of the HERC2 and USP20 interaction."
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"Our study unveils that p38 activation leads to the disruption of the HERC2 and USP20 interaction."
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"This phosphorylation event could trigger the dissociation of the HERC2-USP20 interaction, thereby preventing the ubiquitylation of USP20 by HERC2 and subsequently stabilizing USP20 protein levels."
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"Consistent with this, we found that HERC2 binds the catalytic domain (aa 145–686) of USP20, which includes all four phosphorylation sites."
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"Co-immunoprecipitation assays revealed that both HERC2 and CLASPIN were present in the USP20 immunocomplex and both USP20 and CLASPIN were in the HERC2 immunocomplex, suggesting that HERC2, USP20 and CLASPIN form a complex."
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"HERC2 interacts with USP20, a DUB that is recruited to DSBs and is involved in checkpoint signalling in response to replication stress and HR repair [ xref – xref ]."
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"We found that the presence of USP20 in the HERC2 immunocomplex decreased upon HU treatment, so did the presence of HERC2 in the FALG-USP20 immunocomplex, whereas the interaction between USP20 (4SA) and HERC2 did not decrease in response to HU treatment."
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"In unstressed cells, HERC2 binds USP20 to maintain a low basal level of USP20 in cells."
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"We next studied how HERC2-USP20 interaction is regulated by the DDR pathway."
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"We found that treating cells with the pan PIKK inhibitor caffeine blocked the disassociation of USP20 and HERC2 after UV treatment (Figure xref ), suggesting that PIKKs might be involved in the regulation of USP20-HERC2 interaction."
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"Further mapping of the USP20-HERC2 interaction showed that the enzymatic domain of USP20, is required for the interaction between USP20 and HERC2."
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"On the other hand, USP20 is phosphorylated by ATR, which disrupts the interaction between USP20 and HERC2, resulting in USP20 stabilization."
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"Further mapping of the USP20-HERC2 interaction showed that the enzymatic domain of USP20, is required for the interaction between USP20 and HERC2 (Supplementary Figure S3A)."
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"As USP20 ubiquitination decreases following replication stress, we next studied whether the USP20-HERC2 interaction is subjected to regulation by the DDR pathway."
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"As shown in Figure xref , the interaction between HERC2 and USP20 decreased at early time point following DNA damage and then increased at later time point."
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"We confirmed the interaction between USP20 and HERC2 by endogenous Co-IP."
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"As shown in Figure XREF_FIG, the interaction between HERC2 and USP20 decreased at early time point following DNA damage and then increased at later time point."
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"Mechanistically, the phosphorylation of USP20 by ATR disrupts the interaction between HERC2 and USP20 and is responsible for USP20 upregulation following the DDR."
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"On the other hand, USP20 is phosphorylated by ATR, which disrupts the interaction between USP20 and HERC2, resulting in USP20 stabilization."
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"During cell recovery from genotoxic stress, USP20 binds to HERC2 again and gets degraded."
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"During cell recovery from genotoxic stress, USP20 binds to HERC2 again and gets degraded."
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"Mechanistically, the phosphorylation of USP20 by ATR disrupts the interaction between HERC2 and USP20 and is responsible for USP20 upregulation following the DDR."
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"One is that USP20 phosphorylation itself affects the binding between USP20 and HERC2."
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"Mechanistically, we corroborate an interaction between HERC2 and the deubiquitylating enzyme USP20; and demonstrate that HERC2 deficiency leads to increased USP20 protein levels."
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