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USP27X affects BCL2L11

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USP27X deubiquitinates BCL2L11.

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USP27X deubiquitinates BCL2L11. 7 / 8

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"Furthermore, KD of USP27x blocked ODN-induced Bim expression and deubiquitination of Bim (Fig. 4G and H)."

31901727

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"Overexpression of USP27x combined with ERK1/2 activation to promote the deubiquitylation and stabilisation of BIM and increase caspase‐dependent apoptosis."

28548464

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"Thus, Usp27x can trigger via its proteolytic activity the deubiquitination of Bim and enhance its levels, counteracting the anti-apoptotic effects of ERK activity, and therefore acts as a tumour suppressor."

27013495

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"In addition, ODN dramatically inhibited ubiquitination of Bim, but KD of USP27x blocked ODN-induced deubiquitination of Bim (Fig. 4H)."

31901727

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"Moreover, USP27 deubiquitinates and stabilizes the BH3-only protein Bim, subsequently enhancing apoptosis [14]."

35018513

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"For example, Weber et al. found that wild-type USP27 can reduce the levels of Bim ubiquitination and stabilize Bim in response to the Raf‐ERK‐degradation signal [14]."

35018513

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"Overexpression of USP27x reduced ERK-dependent BIM phosphorylation and ubiquitination in PMA-stimulated cells as well as tumor cells with a constitutively active Raf/ERK pathway."

37584295

Modified USP27X leads to the deubiquitination of BCL2L11. 1 / 1

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"Overexpression of Usp27x reduces ERK dependent Bim ubiquitination, stabilizes phosphorylated Bim, and induces apoptosis in PMA stimulated cells, as well as in tumour cells with a constitutively active Raf and ERK pathway."

27013495

USP27X binds BCL2L11.

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BCL2L11 binds USP27X. 4 / 8

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"Binding of USP27x to BIM was dependent on the 42-101 amino acid region on BIM, as mutation of these sites on BIM disrupted binding to USP27x. xref Interestingly, binding of USP27x and βTrCP to BIM is independent, as knockdown of βTrCP did not reduce the association of BIM with USP27x."

37584295

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"Binding of USP27x to BIM was dependent on the 42-101 amino acid region on BIM, as mutation of these sites on BIM disrupted binding to USP27x."

37584295

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"Furthermore, like βTrCP1/2, the binding of USP27x to BIM was dependent upon ERK1/2 activation."

28548464

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"USP27x, acting as a tumor suppressor, could bind to Bim upon its anti-apoptotic ERK dependent phosphorylation and counteract the following proteasomal degradation via its deubiquitinase activity."

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USP27X binds ERK and BCL2L11. 1 / 1

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"Here, we report the identification of a deubiquitinase, Usp27x, that binds Bim upon its ERK-dependent phosphorylation and can upregulate its expression levels."

27013495

USP27X inhibits BCL2L11.

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USP27X inhibits BCL2L11. 3 / 3

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"These data suggested that Raptor downregulation-mediated mitochondrial ROS production is critical for the enhancement of ODN-induced anti-cancer drugs sensitivity via USP27x-mediated Bim stabilization.3.7 Combined treatment with ODN and TRAIL reduces tumor growth in vivo."

31901727

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"USP27x DUB antagonizes the Raf-ERK Bim degradation pathway thus stabilizing Bim expression."

29479529

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"Loss of endogenous Usp27x enhances the Bim degrading activity of oncogenic Raf."

27013495

USP27X activates BCL2L11.

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USP27X activates BCL2L11. 3 / 3

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"Cathepsin K inhibition-induced mitochondrial ROS enhances sensitivity of cancer cells to anti-cancer drugs through USP27x-mediated Bim protein stabilization."

31901727

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"Our previous study suggested that cathepsin K inhibition enhances anti-cancer drug-induced apoptotic cell death through the upregulation of USP27x-mediated Bim pro-apoptotic protein [12]."

37330581

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"USP27x had no affect the phosphorylation of Bim, but increases stability of Bim by inhibition of ubiquitination [41]."

31901727

USP27X ubiquitinates BCL2L11.

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USP27X leads to the ubiquitination of BCL2L11. 2 / 2

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"Furthermore, KD of USP27x blocked ODN-induced Bim expression and deubiquitination of Bim (Fig. 4G and H)."

31901727

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"In addition, ODN dramatically inhibited ubiquitination of Bim, but KD of USP27x blocked ODN-induced deubiquitination of Bim (Fig. 4H)."

31901727

USP27X decreases the amount of BCL2L11.

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USP27X decreases the amount of BCL2L11. 2 / 2

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"For example, Weber et al. found that wild-type USP27 can reduce the levels of Bim ubiquitination and stabilize Bim in response to the Raf‐ERK‐degradation signal [14]."

35018513

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"Furthermore, KD of USP27x blocked ODN-induced Bim expression and deubiquitination of Bim (Fig. 4G and H)."

31901727

USP27X dephosphorylates BCL2L11.

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USP27X leads to the dephosphorylation of BCL2L11. 1 / 1

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"Overexpression of USP27x reduced ERK-dependent BIM phosphorylation and ubiquitination in PMA-stimulated cells as well as tumor cells with a constitutively active Raf/ERK pathway."

37584295

USP27X affects CBX2

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USP27X binds CBX2.

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USP27X binds CBX2. 10 / 10

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"The interaction between USP27X and CBX2 suggests that USP27X may act as a deubiquitinating enzyme targeting the degradation of CBX2 protein."

38030604

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"Our findings indicate that USP27X truncating mutants lacking the USP domain do not bind CBX2, and that absence of the D1 domain in CBX2 disrupts the binding between USP27X and CBX2 (Fig. 1I–L)."

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"Therefore, the interaction between USP27X and CBX2 requires the presence of the USP domain in USP27X and the D1 domain in CBX2."

38030604

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"The interaction between exogenous USP27X and CBX2 was also verified by immunofluorescence assay in HEK-293T cells (Supplementary Fig. 1D)."

38030604

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"Furthermore, we observed PLA signaling in the nucleus and cytoplasm, providing additional evidence for a direct interaction between endogenous USP27X and CBX2 (Fig. 1F)."

38030604

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"The PLA signal for a direct interaction between exogenous USP27X and CBX2 was detected in HEK-293T cells (Supplementary Fig. 1E)."

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"The upregulation of GSK3β in BT549 cells intensified the association between endogenous USP27X and CBX2 (Fig. 5F), whereas the downregulation of GSK3β in MDA-MB-231 and MCF7 cells weakened the interaction between endogenous USP27X and CBX2 (Fig. 5G, H)."

38030604

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"For example, glycogen synthase kinase 3 beta (GSK3β) can directly bind to and phosphorylate USP27X, thereby enhancing the interaction between USP27X and CBX2 (Xing et al. 2023)."

39522000

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"Furthermore, it has been revealed that glycogen synthase kinase 3 beta (GSK3beta) can directly bind to and phosphorylate USP27X, thereby enhancing the interaction between USP27X and CBX2 and leading to further stabilization of the CBX2 protein."

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"Subsequently, the interaction between USP27X and CBX2 was validated in HEK-293T cells (Supplementary Fig. 1C)."

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USP27X binds CBX2. 3 / 3

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"To evaluate the clinical significance of the USP27X-CBX2 axis and its relevance in BC, we investigated the correlation between USP27X and CBX2 protein expression in human BC specimens."

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"This phosphorylation event enhances the stability of USP27X-CBX2 interaction, thereby promoting CBX2 protein accumulation."

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"The upregulation of GSK3β in BT549 cells intensified the association between endogenous USP27X and CBX2 (Fig. xref ), whereas the downregulation of GSK3β in MDA-MB-231 and MCF7 cells weakened the interaction between endogenous USP27X and CBX2 (Fig. xref G, xref )."

38030604

USP27X activates CBX2.

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USP27X activates CBX2. 5 / 5

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"USP27X enhances CBX2 protein stability."

38030604

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"Similarly, MG132 counteracted the upregulation of CBX2 caused by USP27X overexpression (Fig. 2G, H)."

38030604

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"USP27X promotes the proliferation, invasion, and metastasis of BC cells by up-regulating CBX2."

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"As anticipated, the capacity of USP27X mimetic phosphorylation-inactivated phenotype (USP27X S135A) to sustain CBX2 stability was significantly diminished compared to that of USP27X, while the ability of USP27X mimetic phosphorylation-activated phenotype (USP27X S135Q) to maintain CBX2 stability was considerably augmented (Fig. 5L, M)."

38030604

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"We have demonstrated that the overexpression of USP27X results in an increase in CBX2 levels through deubiquitination, while the deficiency of USP27X promotes CBX2 degradation and restrains tumorigenesis."

38030604

USP27X increases the amount of CBX2.

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USP27X increases the amount of CBX2. 4 / 4

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"One of the key findings in our study is that overexpression of USP27X significantly enhances the level of CBX2 through deubiquitination."

38030604

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"The results showed that USP27X knockdown increased endogenous CBX2 ubiquitination, while USP27X overexpression decreased CBX2 ubiquitination levels (Fig. 3A, B)."

38030604

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"As expected, treatment with the proteasome inhibitor MG132 effectively restored the decreased levels of CBX2 induced by USP27X knockdown, while inhibition of autophagy-lysosomal pathway with CQ failed to exhibit such a restorative effect (Fig. 2F)."

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"Overexpression of USP27X significantly enhances CBX2 levels by promoting deubiquitination, while deficiency of USP27X leads to CBX2 degradation, thereby inhibiting tumorigenesis."

38030604

USP27X deubiquitinates CBX2.

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USP27X deubiquitinates CBX2. 2 / 2

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"The results showed that USP27X knockdown increased endogenous CBX2 ubiquitination, while USP27X overexpression decreased CBX2 ubiquitination levels (Fig. 3A, B)."

38030604

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"USP27X deubiquitinates CBX2."

38030604

USP27X-S135A deubiquitinates CBX2. 1 / 1

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"The deubiquitination of CBX2 by USP27X S135A was found to be impaired in the presence of GSK3β (Fig. 5J), and a similar attenuation of CBX2 deubiquitination was observed upon knockdown of GSK3β (Fig. 5K)."

38030604

USP27X ubiquitinates CBX2.

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USP27X leads to the ubiquitination of CBX2. 1 / 1

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"The results showed that USP27X knockdown increased endogenous CBX2 ubiquitination, while USP27X overexpression decreased CBX2 ubiquitination levels (Fig. 3A, B)."

38030604

USP27X decreases the amount of CBX2.

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USP27X decreases the amount of CBX2. 1 / 1

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"The results showed that USP27X knockdown increased endogenous CBX2 ubiquitination, while USP27X overexpression decreased CBX2 ubiquitination levels (Fig. 3A, B)."

38030604

USP27X affects CCND1

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USP27X binds CCND1.

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USP27X binds CCND1. 6 / 7

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"USP27X interacts with and stabilizes CCND1."

36001804

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"USP27X binds to and stabilizes CCND1 in a catalytically-dependent manner by negatively regulating its ubiquitination."

36001804

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"Here, we demonstrate that USP27X interacts with and stabilizes the proto-oncogene CCND1."

36001804

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"As USP27X would need to physically interact with CCND1 in order to stabilize it, we next tested whether USP27X binds CCND1."

36001804

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"Not only does USP27X bind to CCND1, but USP27X catalytic activity is required for reduction of CCND1 ubiquitination levels and protein stability independent of phosphorylation in cancer cells."

36001804

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"Future studies will elucidate at what stage and in which cellular compartment USP27X interacts with and stabilizes CCND1 and whether additional cofactors or posttranslational modifications are required to facilitate its activity toward this protein."

36001804

USP27X decreases the amount of CCND1.

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USP27X decreases the amount of CCND1. 6 / 6

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"Ablation of USP27X in xenograft tumors reduces CCND1 levels and impairs growth.."

36001804

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"Hence, we next tested whether USP27X ablation, which reduces CCND1 levels, would resensitize HER2 therapy resistant cells to targeted therapy."

36001804

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"Moreover, ablation of USP27X drastically reduces CCND1 levels in these cells and arrests their growth in an Rb1-dependent manner."

36001804

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"The ablation of USP27X markedly reduces CCND1 levels and enhances the sensitivity of BC cells to lapatinib [194]."

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"These experiments revealed that indeed, overexpression of WT but not catalytically inactive USP27X drastically reduces the level of CCND1 ubiquitination (Fig. 3J, compare lanes 7, 8, and 9)."

36001804

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"These data indicated that, indeed, loss of USP27X, which reduces the levels of CCND1, leads to reduction of the CCND1-CDK4/6 complexes and, therefore, loss of Rb1 phosphorylation."

36001804

USP27X increases the amount of CCND1.

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USP27X increases the amount of CCND1. 4 / 4

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"These experiments demonstrated that the expression of WT but not catalytically inactive USP27X can restore the levels of CCND1 in depleted cells (Fig. 3G, compare lanes 2, 3, and 4)."

36001804

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"The expression of exogenous WT USP27X only increased CCND1 levels slightly above the levels in non-depleted, vector only cells (Fig. 3G, lane1)."

36001804

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"As expected, USP27X depletion substantially reduced both CCND1 levels and Rb1 phosphorylation in these cells (Fig. 5E, compare lane 1 to 2)."

36001804

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"These data indicated that, indeed, loss of USP27X, which reduces the levels of CCND1, leads to reduction of the CCND1-CDK4/6 complexes and, therefore, loss of Rb1 phosphorylation."

36001804

USP27X deubiquitinates CCND1.

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USP27X deubiquitinates CCND1. 4 / 4

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"As shown in Figure 3D, USP27X depletion led to a substantial increase in CCND1 ubiquitination (Fig. 3D compare lane 9 to 10)."

36001804

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"To test if USP27X can deubiquitinate CCND1 in cells, we overexpressed WT or CS USP27X in JIMT-1 cells, treated with MG132 to block proteasomal degradation, and monitored CCND1 ubiquitination after protein immunoprecipitation (Fig. 3J)."

36001804

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"These experiments revealed that indeed, overexpression of WT but not catalytically inactive USP27X drastically reduces the level of CCND1 ubiquitination (Fig. 3J, compare lanes 7, 8, and 9)."

36001804

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"Overexpression of USP27X reduces CCND1 ubiquitination and stabilizes the protein, while USP27X ablation reduces CCND1 stability."

36001804

USP27X ubiquitinates CCND1.

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USP27X leads to the ubiquitination of CCND1. 1 / 1

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"Next, we sought to test whether USP27X ablation leads to increased CCND1 ubiquitination."

36001804

USP27X phosphorylates CCND1.

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USP27X leads to the phosphorylation of CCND1. 1 / 1

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"As expected, USP27X depletion substantially reduced both CCND1 levels and Rb1 phosphorylation in these cells (Fig. 5E, compare lane 1 to 2)."

36001804

USP27X inhibits CCND1.

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USP27X inhibits CCND1. 1 / 1

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"As expected, USP27X ablation accelerated the degradation of CCND1 (half-life of ~15 minutes in shProLuc vs. ~8 minutes in shUSP27X), confirming that CCND1 protein stability is compromised upon USP27X loss (Fig. 3E, F)."

36001804

USP27X activates CCND1.

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USP27X activates CCND1. 1 / 1

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"As expected, expression of WT USP27X prolonged CCND1 stability (half-life not detected) while CS USP27X accelerated CCND1 degradation (~18 minutes vs. 15 minutes) (Fig. 3H, compare lanes 3 and 4 to 7, 8,10, 11; Fig 3I)."

36001804

USP27X affects cell population proliferation

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USP27X activates cell population proliferation.

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USP27X activates cell population proliferation. 10 / 20

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"SETD3 reverses the USP27 knockdown mediated blockade of cell proliferation."

35018513

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"These results suggest that USP27X is required to support cancer cell proliferation as opposed to regulating cell death."

36001804

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"To determine how USP27X promotes cancer cell proliferation, we first performed immunoblots comparing the expression of several cell signaling molecules."

36001804

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"Expression of WT-USP27X on its own led to slightly increased proliferation, whereas expression of the C285S mutant led to slightly reduced proliferation."

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"The finding that USP27–SETD3 axis elevates the cell proliferation and migration prompted us to imagine that they might be upregulated in hepatocellular carcinoma."

35018513

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"Upregulation of USP27 in hepatocellular carcinoma patients leads to elevated SETD3 expression and increased cell proliferation, invasion, migration and tumorigenesis."

35018513

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"Furthermore, USP27 or SETD3 knockdown inhibits cell proliferation, cell migration and tumorigenesis, while overexpression of SETD3 in USP27-deficient HCC cells could restore cell viability."

35018513

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"Importantly, expression of WT, but not mutant USP27X, prevented the proliferation defects caused by depletion of endogenous USP27X (XREF_FIG)."

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"Knockdown of USP27 or CTCF in HCC cells considerably decreased glycolysis and proliferation, while overexpression had the opposite effect."

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"Furthermore, evidence from in vitro and in vivo studies revealed that depletion of USP27 inhibited HCC cell proliferation, invasion, metastasis and tumorigenesis, and that overexpression of SETD3 rescued this phenotype."

35018513

USP27X inhibits cell population proliferation.

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Mutated USP27X inhibits cell population proliferation. 1 / 1

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"Importantly, expression of WT, but not mutant USP27X, prevented the proliferation defects caused by depletion of endogenous USP27X (XREF_FIG)."

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USP27X affects Cyclin_E

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USP27X activates Cyclin_E.

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USP27X activates Cyclin_E. 6 / 6

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"USP27 mediated Cyclin E stabilization is involved in tumorigenesis, suggesting that targeting USP27 may represent a new therapeutic strategy to treat cancers with aberrant overexpression of Cyclin E protein."

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"XREF_FIG, catalytically inactive USP27/CA mutant failed to protect Cyclin E from degradation, implying that the DUB activity is required for USP27 mediated Cyclin E stabilization."

29497124

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"Finally, we determined whether USP27 mediated Cyclin E stability is through proteasome."

29497124

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"XREF_FIG, MG132 (proteasome inhibitor) treatment could rescue the USP27 knockdown mediated degradation of Cyclin E protein."

29497124

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"Our discovery that USP27 mediated Cyclin E stabilization implied that USP27 might modulate cell cycle and cell proliferation through Cyclin E regulation."

29497124

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"USP27 mediated Cyclin E stabilization drives cell cycle progression and hepatocellular tumorigenesis."

29497124

USP27X binds Cyclin_E.

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Cyclin_E binds USP27X. 5 / 5

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"Furthermore, USP27x interacts with cyclin E, resulting in stabilization [ xref ]."

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"To further confirm that the interaction between Cyclin E and USP27 was specific, we transfected them alone or together into HEK293T cells and evaluated their interaction by immunoprecipitation and WB."

29497124

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"In addition, we examined whether endogenous Cyclin E interacts with USP27 in the Hep3B cells."

29497124

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"The observation that USP27 interacts with and deubiquitinates Cyclin E led us to think that USP27 might involve in cell cycle progression by regulating Cyclin E stability."

29497124

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"To prevent this degradation, USP27 interacts with and deubiquitinates cyclin E [66]."

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USP27X deubiquitinates Cyclin_E.

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USP27X deubiquitinates Cyclin_E. 3 / 3

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"First, USP27 interacts with and colocalizes with Cyclin E. Second, USP27 negatively regulates Cyclin E ubiquitination."

29497124

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"To prevent this degradation, USP27 interacts with and deubiquitinates cyclin E [66]."

30241373

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"The observation that USP27 interacts with and deubiquitinates Cyclin E led us to think that USP27 might involve in cell cycle progression by regulating Cyclin E stability."

29497124

USP27X inhibits Cyclin_E.

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USP27X inhibits Cyclin_E. 1 / 1

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"Treatment with 5-fluorouracil (5-FU) decreases USP27x expression, and then induces degradation of cyclin E [56]."

31901727

USP27X increases the amount of Cyclin_E.

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USP27X increases the amount of Cyclin_E. 1 / 1

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"Third, USP27 positively regulates Cyclin E protein level."

29497124

USP27X affects SETD3

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USP27X deubiquitinates SETD3.

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USP27X deubiquitinates SETD3. 5 / 5

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"Since USP27 could deubiquitinate and stabilize SETD3, it might promote cell proliferation and migration by regulating SETD3 protein levels."

35018513

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"USP27 inhibits the K48-linkage poly-ubiquitination of SETD3."

35018513

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"Similar results were obtained in the analysis of SETD3.Based on our results, we concluded that SETD3 is deubiquitinated by USP27 and its protein level is positively regulated by and correlated with USP27 expression."

35018513

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"We found that SETD3 was deubiquitinated and stabilized by USP27."

35018513

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"USP27 was able to deubiquitinate and stabilize SETD3."

35018513

USP27X-C87A deubiquitinates SETD3. 1 / 1

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"As seen in Fig. 2C, an enzyme-inactive mutant of USP27 (C87A) failed to abolish the ubiquitination of SETD3 protein compared with the wild-type (WT) USP27, implying that the DUB activity is required for USP27 to remove ubiquitin from SETD3."

35018513

USP27X activates SETD3.

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USP27X activates SETD3. 4 / 4

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"Inhibition of USP27 expression impairs the pro-migratory ability of SETD3."

35018513

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"Since upregulation of SETD3 can promote liver tumorigenesis and cancer progression [12], it is possible that USP27 can also enhance metastatic phenotype by stabilizing SETD3."

35018513

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"Knockdown of USP27 by short hairpin RNA (shRNA) accelerated the degradation of SETD3 and blocked cell proliferation."

35018513

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"In conclusion, our data suggested that USP27 could positively regulate SETD3 protein stability."

35018513

USP27X increases the amount of SETD3.

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USP27X increases the amount of SETD3. 2 / 2

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"As shown in Fig. 3A and B, SETD3 protein expression is significantly upregulated by cotransfection of USP27 and the half-life of the SETD3 protein is dramatically extended by USP27."

35018513

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"Furthermore, ectopic expression of USP27 upregulated endogenous SETD3 protein levels (Fig. 3C and D)."

35018513

USP27X inhibits SETD3.

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USP27X inhibits SETD3. 1 / 1

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"Finally, no obvious change in the mRNA expression levels of SETD3 was observed in the Hep3B cells showing USP27 overexpression (Fig. 3K), suggesting that the regulation of SETD3 protein degradation by USP27 might occur at the post-transcriptional level."

35018513

USP27X binds SETD3.

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SETD3 binds USP27X. 1 / 1

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"To further confirm that the interaction between SETD3 and USP27 was specific, we transfected them alone or together into 293 T cells and evaluated their interaction by immunoprecipitation and western blot."

35018513

CBX2 affects USP27X

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CBX2 binds USP27X.

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USP27X binds CBX2. 10 / 10

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"The interaction between USP27X and CBX2 suggests that USP27X may act as a deubiquitinating enzyme targeting the degradation of CBX2 protein."

38030604

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"Our findings indicate that USP27X truncating mutants lacking the USP domain do not bind CBX2, and that absence of the D1 domain in CBX2 disrupts the binding between USP27X and CBX2 (Fig. 1I–L)."

38030604

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"Therefore, the interaction between USP27X and CBX2 requires the presence of the USP domain in USP27X and the D1 domain in CBX2."

38030604

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"The interaction between exogenous USP27X and CBX2 was also verified by immunofluorescence assay in HEK-293T cells (Supplementary Fig. 1D)."

38030604

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"Furthermore, we observed PLA signaling in the nucleus and cytoplasm, providing additional evidence for a direct interaction between endogenous USP27X and CBX2 (Fig. 1F)."

38030604

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"The PLA signal for a direct interaction between exogenous USP27X and CBX2 was detected in HEK-293T cells (Supplementary Fig. 1E)."

38030604

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38030604

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"For example, glycogen synthase kinase 3 beta (GSK3β) can directly bind to and phosphorylate USP27X, thereby enhancing the interaction between USP27X and CBX2 (Xing et al. 2023)."

39522000

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38030604

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"Subsequently, the interaction between USP27X and CBX2 was validated in HEK-293T cells (Supplementary Fig. 1C)."

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USP27X binds CBX2. 3 / 3

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"To evaluate the clinical significance of the USP27X-CBX2 axis and its relevance in BC, we investigated the correlation between USP27X and CBX2 protein expression in human BC specimens."

38030604

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"This phosphorylation event enhances the stability of USP27X-CBX2 interaction, thereby promoting CBX2 protein accumulation."

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38030604

CBX2 activates USP27X.

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CBX2 activates USP27X. 1 / 1

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"Specifically, while we have identified USP27X as a deubiquitinating enzyme for CBX2 through mass spectrometry analysis, a more comprehensive understanding of the specific ubiquitination sites on CBX2 targeted by USP27X would enhance our knowledge of the underlying regulatory mechanisms."

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USP27X affects Neoplasm Metastasis

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USP27X activates Neoplasm Metastasis.

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USP27X activates Neoplasm Metastasis. 9 / 9

| 1 8

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"How does USP27 promote migration and metastasis?"

29497124

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"Although Cyclin E has been reported to involve in metastasis [XREF_BIBR], how USP27 promotes migration and metastasis also need further detailed exploration."

29497124

➶

reach

"USP27X promotes the proliferation, invasion, and metastasis of BC cells by up-regulating CBX2."

38030604

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reach

"Knockdown of USP27X was found to decrease the incidence of lung metastases from BC cells, while overexpression of USP27X had the opposite effect (Fig. 4L)."

38030604

➶

eidos

"USP27X can also deubiquitinate and stabilize Snail1 when induced by TGF-beta and therefore promotes EMT and tumor metastasis [ 53 ] ."

33466790

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"Instead, overexpression of USP27X‐AS1 increased tumour burden, PCNA and liver metastasis nodules (each group n = 7) (Figure 3G–K)."

38279869

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reach

35018513

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reach

"In vivo studies confirmed that USP27 knockdown suppresses HCC growth and metastasis."

39746496

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"Taken together, these results suggested that USP27 might promote hepatoma metastasis."

29497124

USP27X inhibits Neoplasm Metastasis.

| 1

USP27X inhibits Neoplasm Metastasis. 1 / 1

| 1

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reach

"Down regulation of USP27 suppresses hepatocellular migration and metastasis."

29497124

USP27X affects ATXN7L3

4 | 5 1

USP27X binds ATXN7L3.

4 | 4 1

ATXN7L3 binds USP27X. 3 / 7

4 | 3

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"As expected, ATXN7L3 and ENY2 associated with USP27X and USP51, but no other SAGA components, such as GCN5 or TAF10, were observed in the immunoprecipitations (XREF_FIG, lanes 5 and 6)."

27132940

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"ATXN7L3 and ENY2 associate with USP27X and USP51."

27132940

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reach

"Like USP22, USP27X and USP51 also form complexes with ATXN7L3 and ENY2 and harbor virtually identical catalytic domains ( Atanassov et al., 2016 )."

35452621

USP27X binds ENY2 and ATXN7L3. 1 / 1

| 1

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reach

"In addition, the finding that hD1 inhibits USP27x alone as well as the USP27x/ENY2/ATXN7L3 complex suggest that hD1 inhibits DUB activity by binding directly to the catalytic domain, rather than to the ENY2 and ATXN7L3 subunits."

34936860

ATXN7L3 binds ENY2, USP, USP27X, and USP51. 1 / 1

| 1

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sparser

"A recent study showed that ATXN7L3 and ENY2 can also form complexes with two additional USP DUBs, USP27x and USP51, and target them to H2B-Ub [ xref ]."

27923209

USP27X deubiquitinates ATXN7L3.

| 1

USP27X deubiquitinates ATXN7L3. 1 / 1

| 1

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reach

"Interestingly, USP27x has been reported to deubiquitinate histone H2B-K120 in vivo and in vitro as part of a complex with ATXN7L3 and ENY2 (Atanassov et al., 2016), two of the three adapter proteins that are part of the USP22 DUB module."

34936860

ATXN7L3 affects USP27X

4 | 5 1

ATXN7L3 binds USP27X.

4 | 4 1

ATXN7L3 binds USP27X. 3 / 7

4 | 3

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reach

"As expected, ATXN7L3 and ENY2 associated with USP27X and USP51, but no other SAGA components, such as GCN5 or TAF10, were observed in the immunoprecipitations (XREF_FIG, lanes 5 and 6)."

27132940

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reach

"ATXN7L3 and ENY2 associate with USP27X and USP51."

27132940

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reach

"Like USP22, USP27X and USP51 also form complexes with ATXN7L3 and ENY2 and harbor virtually identical catalytic domains ( Atanassov et al., 2016 )."

35452621

USP27X binds ENY2 and ATXN7L3. 1 / 1

| 1

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34936860

ATXN7L3 binds ENY2, USP, USP27X, and USP51. 1 / 1

| 1

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sparser

"A recent study showed that ATXN7L3 and ENY2 can also form complexes with two additional USP DUBs, USP27x and USP51, and target them to H2B-Ub [ xref ]."

27923209

ATXN7L3 deubiquitinates USP27X.

| 1

ATXN7L3 deubiquitinates USP27X. 1 / 1

| 1

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reach

"Our results now reveal that in addition to USP22, ATXN7L3 and ENY2 activate two previously uncharacterized deubiquitinating enzymes, USP27X and USP51, which are not part of SAGA."

27132940

USP27X affects SNAI1

1 | 8

USP27X deubiquitinates SNAI1.

1 | 4

USP27X deubiquitinates SNAI1. 4 / 5

1 | 4

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"USP27X promotes EMT progression in tumors by deubiquitinating and stabilizing Snail1 [41]."

37894400

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reach

"Another deubiquitinase, USP27X, which was activated by TGFβ, could also deubiquitinate SNAIL1."

32610184

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"USP27X contributes to Snail1 deubiquitination and stabilization, and transforming growth factor-β (TGF-β) is able to promote EMT by upregulating USP27X (Lambies et al., 2019)."

38174069

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"3) Does USP27X require specific cofactors to deubiquitinate Snail1?"

30613357

USP27X activates SNAI1.

| 2

USP27X activates SNAI1. 2 / 2

| 2

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"Lambies et al. showed that in breast and pancreatic cancer cell lines, TGF-β signaling during EMT contributes to cisplatin resistance by upregulating the expression of USP27X, which increases Snail1 protein stability (38)."

38592373

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reach

"USP27X can be deubiquitinated in tumor cells and thus increase Snail1 stability ( Lambies et al., 2019 )."

37001578

USP27X increases the amount of SNAI1.

| 1

USP27X increases the amount of SNAI1. 1 / 1

| 1

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reach

"Thus, USP27X depletion reduced SNAIL1 levels and eventually prevented TGFβ-induced EMT and fibroblast activation [ 69 ]."

32610184

USP27X binds SNAI1.

| 1

SNAI1 binds USP27X. 1 / 1

| 1

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reach

"In TNBC, but not in HER2-positive tumors, there is a significant association between Snail1 and USP27X."

36179816

USP27X affects HYCC1

| 9

USP27X activates HYCC1.

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USP27X activates HYCC1. 8 / 8

| 8

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"We also found that the levels of SETD3 and USP27 increased significantly in HCC than those in the relevant adjacent tissues."

35018513

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reach

"These results indicate that depletion of USP27 also inhibited HCC cell growth in vivo."

35018513

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reach

35018513

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reach

"USP27 knockdown inhibits HCC cell growth in vivo."

35018513

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reach

"In vivo studies confirmed that USP27 knockdown suppresses HCC growth and metastasis."

39746496

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reach

"In conclusion, USP27X‐AS1 upregulated AKT protein expression by recruiting USP7 to deubiquitinate AKT.3.6 USP27X-AS1 promoted HCC progression by regulating AKT."

38279869

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"To verify whether USP27X‐AS1 promoted HCC progression via AKT, we transfected Flag‐AKT into USP27X‐AS1 knockdown cells and used AKT‐siRNA to interfere with AKT expression in USP27X‐AS1 overexpressed cells."

38279869

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reach

"To unravel the mechanism by which USP27X‐AS1 promotes HCC, we conducted RNA‐seq on HLF cells with USP27X‐AS1 overexpression and the control counterparts."

38279869

USP27X inhibits HYCC1.

| 1

USP27X inhibits HYCC1. 1 / 1

| 1

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"CCK‐8 assay, EdU assay and colony‐formation assay showed that overexpression of AKT could reverse the inhibition of HCC proliferation caused by decreasing USP27X‐AS1 (Figure 6A,B,E,F,I,J and Figure S8I,K), while USP27X‐AS1 lost the ability to promote HCC proliferation upon decreasing AKT (Figure 6C,D,G,H,K,L and Figure S8J,L)."

38279869

BCL2L11 affects USP27X

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BCL2L11 binds USP27X. 4 / 8

4 | 3 1

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37584295

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"Binding of USP27x to BIM was dependent on the 42-101 amino acid region on BIM, as mutation of these sites on BIM disrupted binding to USP27x."

37584295

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reach

"Furthermore, like βTrCP1/2, the binding of USP27x to BIM was dependent upon ERK1/2 activation."

28548464

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"USP27x, acting as a tumor suppressor, could bind to Bim upon its anti-apoptotic ERK dependent phosphorylation and counteract the following proteasomal degradation via its deubiquitinase activity."

28279784

USP27X binds ERK and BCL2L11. 1 / 1

| 1

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"Here, we report the identification of a deubiquitinase, Usp27x, that binds Bim upon its ERK-dependent phosphorylation and can upregulate its expression levels."

27013495

USP27X affects apoptotic process

| 8

USP27X activates apoptotic process.

| 7

USP27X activates apoptotic process. 6 / 6

| 6

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"Overexpression of USP27x combined with ERK1/2 activation to promote the deubiquitylation and stabilisation of BIM and increase caspase‐dependent apoptosis."

28548464

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"The deubiquitinase Usp27x stabilizes the BH3-only protein Bim and enhances apoptosis."

27013495

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"However, the authors also found that overexpression of USP27x combined with ERK1/2 pathway inhibition to promote apoptosis."

28548464

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"Finally, deletion of Usp27x reduces apoptosis in NSCLC cells treated with an EGFR inhibitor."

27013495

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"Weber et al. reported that USP27x stabilizes Bim and induces apoptosis [41]."

31901727

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"Overexpression of Usp27x induces low levels of apoptosis in melanoma and non small cell lung cancer (NSCLC) cells and substantially enhances apoptosis induced in these cells by the inhibition of ERK signalling."

27013495

Modified USP27X activates apoptotic process. 1 / 1

| 1

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27013495

USP27X inhibits apoptotic process.

| 1

USP27X inhibits apoptotic process. 1 / 1

| 1

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"In addition, in NSCLC cells, depletion of USP27x reduces apoptosis when treated with an EGFR inhibitor."

28279784

USP27X affects Neoplasm Invasiveness

| 8

USP27X activates Neoplasm Invasiveness. 8 / 8

| 8

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"USP27X modulates tumor chemoresistance and invasion through deubiquitination and stabilization of Snail1 XREF_BIBR."

33391500

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reach

35018513

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"Conversely, overexpression of USP27 evidently enhanced cell invasion."

29497124

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"Taken together, these data revealed that knockdown of USP27 or SETD3 prevents liver cancer cell migration and invasion."

35018513

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reach

"USP27X promotes the proliferation, invasion, and metastasis of BC cells by up-regulating CBX2."

38030604

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reach

"Upregulation of USP27 in hepatocellular carcinoma patients leads to elevated SETD3 expression and increased cell proliferation, invasion, migration and tumorigenesis."

35018513

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"Transwell assay and wound‐healing assay indicated that the impaired migration and invasion ability caused by USP27X‐AS1 knockdown could be reversed by AKT overexpression (Figure 6M,N,Q,R and Figure S9A,C)."

38279869

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"Transwell and wound‐healing assays indicated that USP27X‐AS1 overexpression enhanced the migration and invasion abilities of HLF and Hep3B cells (Figure 2G–J and Figure S3G–J), whereas USP27X‐AS1 knockdown diminished these capabilities in MHCC97H and LM3 cells (Figure 2G–J and Figure S3G–J)."

38279869

USP27X affects AKT

| 8

USP27X activates AKT.

| 3

USP27X activates AKT. 3 / 3

| 3

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"Taken together, USP27X‐AS1 upregulated AKT signalling via interacting with AKT protein.3.5 USP27X-AS1 inhibited AKT proteasome degradation."

38279869

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reach

"In conclusion, USP27X‐AS1 upregulated AKT protein expression by recruiting USP7 to deubiquitinate AKT.3.6 USP27X-AS1 promoted HCC progression by regulating AKT."

38279869

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reach

"Results showed that USP27X‐AS1 knockdown impaired AKT protein stability (Figure 5A1,B1 and Figure S5A1,B1), while USP27X‐AS1 overexpression prolonged the half‐life of AKT (Figure 5A2,B2 and Figure S5A2,B2), suggesting that USP27X‐AS1 might inhibit AKT degradation."

38279869

USP27X increases the amount of AKT.

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USP27X increases the amount of AKT. 2 / 2

| 2

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"All these results confirmed that USP27X‐AS1 recruited USP7 to bind AKT.Furthermore, decreasing USP7 expression using siRNAs downregulated AKT protein expression (Figure 5J and Figure S6I), while overexpression of USP7 increased AKT protein expression (Figure 5K)."

38279869

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"Western blot analysis showed that USP27X‐AS1 could not upregulate AKT protein expression and poly‐ubiquitination level upon USP7 deficiency (Figure 5P and Figure S6L,M)."

38279869

USP27X decreases the amount of AKT.

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USP27X decreases the amount of AKT. 2 / 2

| 2

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38279869

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"Results showed that only MG132 could effectively restore the protein level of AKT decreased by USP27X‐AS1 knockdown (Figure 5C and Figure S5C)."

38279869

USP27X deubiquitinates AKT.

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USP27X leads to the deubiquitination of AKT. 1 / 1

| 1

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"Mechanistically, USP27X‐AS1 enhances USP7‐mediated deubiquitination and upgrading of AKT to promote HCC progression; we also showed that SP1 binds to the promoter of USP27X‐AS1, enhances USP27X‐AS1 transcription, revealing a novel regulatory axis of SP1‐USP27X‐AS1‐USP7‐AKT in HCC."

38279869

TGFB affects USP27X

| 3 5

TGFB activates USP27X.

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TGFB activates USP27X. 7 / 7

| 3 4

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"USP27X was upregulated by TGFbeta during EMT and was required for TGFbeta induced expression of Snail1 and other mesenchymal markers in epithelial cells and CAF."

30341066

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eidos

"TGFbeta enhances USP27X expression that deubiquitinates and stabilizes Snail1 , which in turn induces EMT in cancer cells and activation of CAFs ."

30613357

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eidos

"TGFbeta also induces USP27X expression , which increases SNAI1 stability by deubiquitination [ 55 ] ."

| PMC

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"In fact, DUBs involved in Snail regulation so far are shown to be induced differently, while USP27x is induced by TGF-β; DUB3/USP17L2 seems to play a role in CDK4/6-mediated activation of EMT, whereas OTUB1 is under the transcriptional regulation of oestrogen-related receptor alpha, and USP37 regulation is induced during EMT via the stimulation of the hedgehog signalling pathway."

32636467

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eidos

"USP27X can also deubiquitinate and stabilize Snail1 when induced by TGF-beta and therefore promotes EMT and tumor metastasis [ 53 ] ."

33466790

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reach

"TGFbeta activated USP27X deubiquitinase regulates cell migration and chemoresistance via stabilization of Snail1."

30341066

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"TGF-β upregulated USP27X during EMT, and it was essential for Snail1 and other mesenchymal markers to be expressed in epithelial cells and CAF."

36179816

TGFB increases the amount of USP27X.

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TGFB increases the amount of USP27X. 1 / 1

| 1

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"Specifically, DUB3 was shown to respond to IL-6-stimulated transcriptional activation and stabilize Snail1 in breast cancer cells; while USP27X expression was reported to be induced by TGFβ, which assisted the upregulation of Snail1 and other mesenchymal genes ."

32968046

GSK3B affects USP27X

| 6 2

GSK3B phosphorylates USP27X.

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GSK3B phosphorylates USP27X. 4 / 4

| 4

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"For example, glycogen synthase kinase 3 beta (GSK3β) can directly bind to and phosphorylate USP27X, thereby enhancing the interaction between USP27X and CBX2 (Xing et al. 2023)."

39522000

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reach

38030604

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"GSK3beta enhances the stability of CBX2 protein by phosphorylating USP27X."

38030604

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"Phosphorylation of USP27X by GSK3beta maintains the stability and oncogenic functions of CBX2."

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GSK3B phosphorylates USP27X. 1 / 1

| 1

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"Additionally, we have discovered a direct interaction between GSK3β and USP27X, where GSK3β phosphorylates USP27X to enhance its affinity for CBX2 and further stabilize CBX2 protein levels."

38030604

GSK3B binds USP27X.

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GSK3B binds USP27X. 2 / 2

| 2

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38030604

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"For example, glycogen synthase kinase 3 beta (GSK3β) can directly bind to and phosphorylate USP27X, thereby enhancing the interaction between USP27X and CBX2 (Xing et al. 2023)."

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GSK3B binds USP27X. 1 / 1

| 1

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"Additionally, we have discovered a direct interaction between GSK3β and USP27X, where GSK3β phosphorylates USP27X to enhance its affinity for CBX2 and further stabilize CBX2 protein levels."

38030604

CCND1 affects USP27X

1 | 7

CCND1 binds USP27X.

1 | 6

USP27X binds CCND1. 6 / 7

1 | 6

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"USP27X interacts with and stabilizes CCND1."

36001804

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"USP27X binds to and stabilizes CCND1 in a catalytically-dependent manner by negatively regulating its ubiquitination."

36001804

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"Here, we demonstrate that USP27X interacts with and stabilizes the proto-oncogene CCND1."

36001804

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reach

"As USP27X would need to physically interact with CCND1 in order to stabilize it, we next tested whether USP27X binds CCND1."

36001804

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reach

"Not only does USP27X bind to CCND1, but USP27X catalytic activity is required for reduction of CCND1 ubiquitination levels and protein stability independent of phosphorylation in cancer cells."

36001804

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36001804

CCND1 activates USP27X.

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CCND1 activates USP27X. 1 / 1

| 1

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"Additionally, expression of ectopic CCND1 almost completely rescued the growth defects in USP27X-depleted cells (Supplementary Fig. 5)."

36001804

USP27X affects TRIM28

1 | 1 5

USP27X binds TRIM28.

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USP27X binds TRIM28. 5 / 6

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"Usp27x interacts with the E3-ubiquitin ligase TRIM28, and TRIM28 deficiency blocks Usp27x-induced loss of cFLIP L level and apoptosis induction by pIC."

35044632

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"We also could not detect an interaction between endogenous Usp27x and TRIM28 in WM1158 cells (data not shown), and Usp27x-deficient WM1158 cells were not protected from pIC-induced apoptotic cell death (Fig. xref E)."

35044632

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"However, in 293FT, which express substantially more Usp27x L (Fig. xref B), the interaction between endogenous Usp27x and TRIM28 could be observed by IP (Fig. xref D)."

35044632

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"At endogenous levels, the interaction between Usp27x L and TRIM28 was detected in 293FT cells (Fig. xref D), but not in WM1158 cells (data not shown), which express substantially less Usp27x L compared to 293FT cells (Fig. xref B)."

35044632

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"Instead, Usp27x interacted with the E3-ligase TRIM28 and reduced ubiquitination of TRIM28."

35044632

USP27X deubiquitinates TRIM28.

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USP27X leads to the deubiquitination of TRIM28. 1 / 1

| 1

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"Instead, Usp27x interacted with the E3-ligase TRIM28 and reduced ubiquitination of TRIM28."

35044632

USP27X affects ENY2

1 | 5 1

USP27X binds ENY2.

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ENY2 binds USP27X. 3 / 4

1 | 3

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"As expected, ATXN7L3 and ENY2 associated with USP27X and USP51, but no other SAGA components, such as GCN5 or TAF10, were observed in the immunoprecipitations (XREF_FIG, lanes 5 and 6)."

27132940

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"ATXN7L3 and ENY2 associate with USP27X and USP51."

27132940

➶

reach

"Like USP22, USP27X and USP51 also form complexes with ATXN7L3 and ENY2 and harbor virtually identical catalytic domains ( Atanassov et al., 2016 )."

35452621

USP27X binds ENY2 and ATXN7L3. 1 / 1

| 1

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34936860

ATXN7L3 binds ENY2, USP, USP27X, and USP51. 1 / 1

| 1

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"A recent study showed that ATXN7L3 and ENY2 can also form complexes with two additional USP DUBs, USP27x and USP51, and target them to H2B-Ub [ xref ]."

27923209

USP27X deubiquitinates ENY2.

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USP27X deubiquitinates ENY2. 1 / 1

| 1

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34936860

USP27X affects CGAS

| 7

USP27X deubiquitinates CGAS.

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USP27X deubiquitinates CGAS. 3 / 3

| 3

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"Guo et al. have reported that cGAS can be deubiquitinated by USP27X, thereby promoting the stability of cGAS protein and increasing cGAMP expression [22] ."

37478666

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"Cutting Edge : USP27X Deubiquitinates and Stabilizes the DNA Sensor cGAS to Regulate Cytosolic DNA Mediated Signaling."

31534008

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reach

"USP27X and USP29 have a similar mechanism for the deubiquitination of cGAS, both preventing the degradation of cGAS via the proteasomal pathway by removing the K48-linked ubiquitin chain of cGAS and maintaining cGAS protein levels."

36579404

USP27X binds CGAS.

| 3

USP27X binds CGAS and K48. 3 / 3

| 3

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"Furthermore, the deubiquitinating enzyme USP27X associates with cGAS and eliminates K48-linked polyubiquitinated chains from cGAS, leading to the stability of cGAS (24)."

40028324

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reach

"In this study, we identified that deubiquitinase USP27X could interact with cGAS and cleave K48 linked polyubiquitination chains from cGAS, leading to cGAS stabilization."

31534008

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reach

"Unlike USP14, USP27x directly interacts with cGAS and releases the K48 linked polyubiquitin chains during viral infection."

33511009

USP27X activates CGAS.

| 1

USP27X activates CGAS. 1 / 1

| 1

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"The E3 ubiquitin ligases TRIM41 and TRIM56 augment dimerization, DNA-binding activity, and cGAMP synthesis; RNF185, and the deubiquitinating enzymes USP15 and USP27X promote cGAS stability (13, 17, 19, 23, 24)."

40028324

HDAC1 affects USP27X

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HDAC1 inhibits USP27X. 7 / 7

| 2 2 3

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"As shown in xref , hD1 inhibits the USP27x complex at >25-fold higher inhibitor concentrations and modestly inhibits the USP51 complex only at >2500-fold higher concentration than that needed to inhibit the human DUB module."

34936860

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sparser

34936860

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sparser

"Since hD1 inhibits USP27x whether or not it is in complex with the other SAGA subunits, the inhibitor likely binds directly to the catalytic USP domain."

34936860

➶

eidos

"In addition , the finding that hD1 inhibits USP27x alone as well as the USP27x / ENY2 / ATXN7L3 complex suggest that hD1 inhibits DUB activity by binding directly to the catalytic domain , rather than to the ENY2 and ATXN7L3 subunits ."

34936860

➶

reach

"As shown in Figure 5B, hD1 inhibits the USP27x complex at >25-fold higher inhibitor concentrations and modestly inhibits the USP51 complex only at >2500-fold higher concentration than that needed to inhibit the human DUB module."

34936860

➶

eidos

"Since hD1 inhibits USP27x whether or not it is in complex with the other SAGA subunits , the inhibitor likely binds directly to the catalytic USP domain ."

34936860

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reach

"Since hD1 inhibits USP27x whether or not it is in complex with the other SAGA subunits, the inhibitor likely binds directly to the catalytic USP domain."

34936860

ENY2 affects USP27X

1 | 5 1

ENY2 binds USP27X.

1 | 4 1

ENY2 binds USP27X. 3 / 4

1 | 3

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"As expected, ATXN7L3 and ENY2 associated with USP27X and USP51, but no other SAGA components, such as GCN5 or TAF10, were observed in the immunoprecipitations (XREF_FIG, lanes 5 and 6)."

27132940

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reach

"ATXN7L3 and ENY2 associate with USP27X and USP51."

27132940

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reach

"Like USP22, USP27X and USP51 also form complexes with ATXN7L3 and ENY2 and harbor virtually identical catalytic domains ( Atanassov et al., 2016 )."

35452621

USP27X binds ENY2 and ATXN7L3. 1 / 1

| 1

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34936860

ATXN7L3 binds ENY2, USP, USP27X, and USP51. 1 / 1

| 1

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sparser

"A recent study showed that ATXN7L3 and ENY2 can also form complexes with two additional USP DUBs, USP27x and USP51, and target them to H2B-Ub [ xref ]."

27923209

ENY2 deubiquitinates USP27X.

| 1

ENY2 deubiquitinates USP27X. 1 / 1

| 1

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"Our results now reveal that in addition to USP22, ATXN7L3 and ENY2 activate two previously uncharacterized deubiquitinating enzymes, USP27X and USP51, which are not part of SAGA."

27132940

USP27X affects cell growth

| 6

USP27X inhibits cell growth.

| 3

USP27X inhibits cell growth. 3 / 3

| 3

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"As shown in Figures 5I, J, L and M, expression of WT USP27X led to a significant increase in colony number, while expression of the catalytically inactive DUB suppressed cell growth in both lines."

36001804

➶

reach

"Ablation of USP27X leads to enhanced CCND1 ubiquitination, a drastic reduction in CCND1 protein levels, and abrogated cell growth in several cancer cell lines, including HER2 therapy resistant breast cancer cells and xenograft tumors."

36001804

➶

reach

"These experiments confirmed that ablation of USP27X strongly impairs cell growth, whereas ATXN7L3 depletion has no impact (Supplementary Fig. 1)."

36001804

USP27X activates cell growth.

| 3

USP27X activates cell growth. 3 / 3

| 3

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reach

"These results indicate that depletion of USP27 also inhibited HCC cell growth in vivo."

35018513

➶

reach

"USP27 knockdown inhibits HCC cell growth in vivo."

35018513

➶

reach

"Herein, we demonstrate that USP27 regulates Cyclin E abundance to accelerate cell cycle progression, cell proliferation, and tumor cell growth as well."

29497124

TRIM28 affects USP27X

1 | 5

USP27X binds TRIM28. 5 / 6

1 | 5

➶

sparser

"Usp27x interacts with the E3-ubiquitin ligase TRIM28, and TRIM28 deficiency blocks Usp27x-induced loss of cFLIP L level and apoptosis induction by pIC."

35044632

➶

sparser

35044632

➶

sparser

"However, in 293FT, which express substantially more Usp27x L (Fig. xref B), the interaction between endogenous Usp27x and TRIM28 could be observed by IP (Fig. xref D)."

35044632

➶

sparser

35044632

➶

sparser

"Instead, Usp27x interacted with the E3-ligase TRIM28 and reduced ubiquitination of TRIM28."

35044632

Cyclin_E affects USP27X

| 5 1

Cyclin_E binds USP27X.

| 4 1

Cyclin_E binds USP27X. 5 / 5

| 4 1

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sparser

"Furthermore, USP27x interacts with cyclin E, resulting in stabilization [ xref ]."

31901727

➶

reach

29497124

➶

reach

"In addition, we examined whether endogenous Cyclin E interacts with USP27 in the Hep3B cells."

29497124

➶

reach

"The observation that USP27 interacts with and deubiquitinates Cyclin E led us to think that USP27 might involve in cell cycle progression by regulating Cyclin E stability."

29497124

➶

reach

"To prevent this degradation, USP27 interacts with and deubiquitinates cyclin E [66]."

30241373

Cyclin_E inhibits USP27X.

| 1

Cyclin_E inhibits USP27X. 1 / 1

| 1

➶

reach

"Interestingly, USP27 expression might also be regulated by Fbxw7, a well-known E3 ubiquitin ligase of Cyclin E, which interacts with and degrades USP27."

29497124

USP27X affects cell cycle

| 5

USP27X activates cell cycle. 5 / 5

| 5

➶

reach

"Herein, we demonstrate that USP27 regulates Cyclin E abundance to accelerate cell cycle progression, cell proliferation, and tumor cell growth as well."

29497124

➶

reach

"XREF_FIG, USP27 knockdown suppresses cell cycle progression by increasing the percentage of cells in G1/S phase but decreasing the percentage of cells in G2/M phase, similar to 5-FU treatment."

29497124

➶

reach

"We found that USP27 knockdown suppresses cell cycle progression by increasing the percentage of cells in G0/G1 phase, which can be reversed by the addition of Cyclin E expression."

29497124

➶

reach

"To further support our notion that USP27 promotes cell cycle progression, we detected a statistically significant reduction in the growth of Hep3B and MHCC97H cells compared with that of control cells with single stable knockdown of USP27."

29497124

➶

reach

"The observation that USP27 promotes cell cycle progression and cell proliferation prompted us to imagine that depletion of USP27 expression might suppress tumor progression."

29497124

USP51 affects USP27X

| 4

USP27X binds USP51. 2 / 2

| 2

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sparser

"Interestingly, one of the USP27X and USP51 associated proteins, C1QBP, was originally described as a mitochondrial protein ( xref )."

27132940

➶

sparser

"The reduced tumor burden upon depletion of USP27X prompted us to search the The Cancer Genome Atlas (TCGA) database to see if altered expression of USP27X or USP51 is associated with certain cancer phenotypes."

27132940

USP27X binds USP51 and USP22. 1 / 1

| 1

➶

sparser

"Due to the lack of ChIP grade antibodies, we have not yet been able to define loci directly bound by USP27X, USP51, or USP22, so we cannot specify genes and pathways directly governed by these DUBs."

27132940

ATXN7L3 binds ENY2, USP, USP27X, and USP51. 1 / 1

| 1

➶

sparser

"A recent study showed that ATXN7L3 and ENY2 can also form complexes with two additional USP DUBs, USP27x and USP51, and target them to H2B-Ub [ xref ]."

27923209

USP27X affects epithelial to mesenchymal transition

| 1 3

USP27X activates epithelial to mesenchymal transition. 4 / 4

| 1 3

➶

reach

"USP27X contributes to Snail1 deubiquitination and stabilization, and transforming growth factor-β (TGF-β) is able to promote EMT by upregulating USP27X (Lambies et al., 2019)."

38174069

➶

eidos

"USP27X can also deubiquitinate and stabilize Snail1 when induced by TGF-beta and therefore promotes EMT and tumor metastasis [ 53 ] ."

33466790

➶

reach

"Depletion of USP27X inhibited TGF-β-induced EMT and fibroblast activation, which is consistent with this [ 71 ]."

36179816

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reach

"The inhibition of USP27X leads to Snail1 destabilization, suppresses EMT and renders tumor cells sensitive to chemotherapy (75)."

35616129

USP27X affects cell migration

| 4

USP27X activates cell migration.

| 3

USP27X activates cell migration. 3 / 3

| 3

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reach

"To explore the roles of the USP27–SETD3 axis in cell migration and invasion, we performed the wound-healing assay and the results showed that knockdown of SETD3 or USP27 significantly inhibited cell migration compared to that in the control cells, whereas introducing SETD3 into USP27 knockdown cells partially restored the metastatic phenotype (Fig. 6A-D)."

35018513

➶

reach

"Taken together, these data revealed that knockdown of USP27 or SETD3 prevents liver cancer cell migration and invasion."

35018513

➶

reach

"Furthermore, USP27 or SETD3 knockdown inhibits cell proliferation, cell migration and tumorigenesis, while overexpression of SETD3 in USP27-deficient HCC cells could restore cell viability."

35018513

USP27X inhibits cell migration.

| 1

USP27X inhibits cell migration. 1 / 1

| 1

➶

reach

"As shown in Figure S5A-D, depletion of USP27 expression significantly decreased cell migration compared with the control in Hep3B and MHCC97H cells using wound healing assay."

29497124

USP27X affects USP51

| 4

USP27X binds USP51. 2 / 2

| 2

➶

sparser

"Interestingly, one of the USP27X and USP51 associated proteins, C1QBP, was originally described as a mitochondrial protein ( xref )."

27132940

➶

sparser

27132940

USP27X binds USP51 and USP22. 1 / 1

| 1

➶

sparser

27132940

ATXN7L3 binds ENY2, USP, USP27X, and USP51. 1 / 1

| 1

➶

sparser

"A recent study showed that ATXN7L3 and ENY2 can also form complexes with two additional USP DUBs, USP27x and USP51, and target them to H2B-Ub [ xref ]."

27923209

USP27X affects Neoplasms

| 4

USP27X activates Neoplasms. 4 / 4

| 4

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"Importantly, dox-induced depletion of USP27X significantly impaired further tumor development."

36001804

➶

reach

"The results of this study indicate that knockdown of USP27X in MDA-MB-231 cells inhibits proliferation, whereas overexpression of USP27X in BT549 cells promotes tumor growth."

38030604

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reach

"In vivo experiments also demonstrated that knockdown of USP27X suppressed tumor proliferation in xenograft models (Fig. 4F–H), while overexpression of USP27X promoted tumor proliferation in BT549 xenograft models (Fig. 4I–K)."

38030604

➶

reach

"Collectively, we revealed that USP27 exerts tumor-promoting action by modulating the USP27–SETD3 axis.Studies have validated that USP22, the USP27 homologous protein, has similar effects with USP27 [16, 21, 22]."

35018513

USP27X affects HES1

1 | 3

USP27X deubiquitinates HES1. 3 / 4

1 | 3

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"Another study demonstrated that USP27x, Usp22, and Usp51 deubiquitinate and stabilize Hes1 protein, a transcriptional repressor necessary for the maintenance of neural stem/progenitor cells."

38952059

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reach

"We found that Hes1 was deubiquitinated and stabilized by Usp27x and its homologs ubiquitin specific protease 22 (Usp22) and ubiquitin specific protease 51 (Usp51)."

25846153

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reach

"In addition, USP27 could regulate neuronal differentiation of stem cells in the developing mouse neocortex by deubiquitinating and stabilizing Hes1 [22]."

35018513

USP27X affects Carcinogenesis

| 4

USP27X activates Carcinogenesis.

| 3

USP27X activates Carcinogenesis. 3 / 3

| 3

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35018513

➶

reach

"Furthermore, USP27 or SETD3 knockdown inhibits cell proliferation, cell migration and tumorigenesis, while overexpression of SETD3 in USP27-deficient HCC cells could restore cell viability."

35018513

➶

reach

"Upregulation of USP27 in hepatocellular carcinoma patients leads to elevated SETD3 expression and increased cell proliferation, invasion, migration and tumorigenesis."

35018513

USP27X inhibits Carcinogenesis.

| 1

USP27X inhibits Carcinogenesis. 1 / 1

| 1

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reach

"Overexpression of USP27X significantly enhances CBX2 levels by promoting deubiquitination, while deficiency of USP27X leads to CBX2 degradation, thereby inhibiting tumorigenesis."

38030604

USP22 affects USP27X

| 2 2

USP22 binds USP27X.

| 2

USP27X binds USP51 and USP22. 1 / 1

| 1

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sparser

27132940

USP27X binds USP22. 1 / 1

| 1

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sparser

"All these results indicate that USP27X and the close homologue USP22 specifically interact and stabilize Snail1."

30341066

USP22 inhibits USP27X.

| 1

USP22 inhibits USP27X. 1 / 1

| 1

➶

reach

"To determine whether USP22 blocks association of USP27X and USP51 with SAGA, we isolated GCN5 associated proteins after shRNA mediated depletion of USP22 (XREF_FIG, lanes 2 and 3 and 5 and 6)."

27132940

USP22 activates USP27X.

| 1

USP22 activates USP27X. 1 / 1

| 1

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reach

"Equal numbers of cells expressing shRNAs that specifically target USP27X or USP51, but not USP22 (XREF_FIG), or expressing control shRNA, were seeded and monitored for proliferation by cell counts 72 hours later."

27132940

ODN affects USP27X

| 4

ODN increases the amount of USP27X.

| 3

ODN increases the amount of USP27X. 3 / 3

| 3

➶

reach

"As shown in Fig. 4D, ODN markedly increased USP27x expression, but not USP9x."

31901727

➶

reach

"However, ODN only increased USP27x expression within 3 h (Fig. 4D), and KD or KO of Cat K also induced USP27x expression (Fig. 4E and F)."

31901727

➶

reach

"Furthermore, ODN-mediated mitochondrial ROS production induced USP27x expression."

31901727

ODN activates USP27X.

| 1

ODN activates USP27X. 1 / 1

| 1

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reach

"Up-regulation of USP27x by ODN is associated with the up-regulation of Bim expression, which is critical for ODN-induced chemosensitivity of cancer cells (Fig. 8)."

31901727

USP27X is modified

| 4

USP27X is phosphorylated. 4 / 4

| 4

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"The phosphorylation of USP27X was solely observed in HEK-293T cells that were transfected with the wild-type USP27X, and not with the S135A mutant (Fig. xref )."

38030604

➶

sparser

"Moreover, while our study highlights the role of GSK3β in phosphorylating USP27X and enhancing its affinity for CBX2, the downstream signaling events triggered by this interaction remain largely unexplored."

38030604

➶

sparser

"GSK3β enhances the stability of CBX2 protein by phosphorylating USP27X."

38030604

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sparser

"These findings suggest that GSK3β-mediated phosphorylation of USP27X is indispensable for its binding and deubiquitination with CBX2."

38030604

GSK3 affects USP27X

| 4

GSK3 phosphorylates USP27X. 4 / 4

| 4

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"For example, glycogen synthase kinase 3 beta (GSK3β) can directly bind to and phosphorylate USP27X, thereby enhancing the interaction between USP27X and CBX2 (Xing et al. 2023)."

39522000

➶

reach

"These findings suggest that GSK3β-mediated phosphorylation of USP27X is indispensable for its binding and deubiquitination with CBX2."

38030604

➶

reach

"Additionally, we have discovered a direct interaction between GSK3β and USP27X, where GSK3β phosphorylates USP27X to enhance its affinity for CBX2 and further stabilize CBX2 protein levels."

38030604

➶

reach

"Our study also elucidates the involvement of GSK3β in modulating the GSK3β-USP27X-CBX2 axis, revealing that GSK3β can directly interact with and phosphorylate USP27X, thereby enhancing its binding affinity for CBX2."

38030604

USP27X affects glycolytic process

| 3

USP27X activates glycolytic process. 3 / 3

| 3

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"Knockdown of USP27 or CTCF in HCC cells considerably decreased glycolysis and proliferation, while overexpression had the opposite effect."

39746496

➶

reach

"USP27 promotes glycolysis and hepatocellular carcinoma progression by stabilizing PFKFB3 through deubiquitination."

39746496

➶

reach

"Phosphorylation of USP27X by PIM2 promotes glycolysis and breast cancer progression via deubiquitylation of MYC."

38969771

USP27X affects RIGI

1 | 2

USP27X deubiquitinates RIGI.

1 | 1

USP27X leads to the deubiquitination of RIGI. 1 / 2

1 | 1

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"Additionally, ubiquitination assays demonstrated that USP27X reduced RIG-I ubiquitination, specifically the K63-ubiquitin linkage type."

33530371

USP27X ubiquitinates RIGI.

| 1

USP27X leads to the ubiquitination of RIGI. 1 / 1

| 1

➶

reach

"USP27X negatively regulates antiviral signaling by deubiquitinating RIG-I."

32027733

USP27X affects K48

| 3

USP27X binds CGAS and K48. 3 / 3

| 3

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reach

"Furthermore, the deubiquitinating enzyme USP27X associates with cGAS and eliminates K48-linked polyubiquitinated chains from cGAS, leading to the stability of cGAS (24)."

40028324

➶

reach

"In this study, we identified that deubiquitinase USP27X could interact with cGAS and cleave K48 linked polyubiquitination chains from cGAS, leading to cGAS stabilization."

31534008

➶

reach

"Unlike USP14, USP27x directly interacts with cGAS and releases the K48 linked polyubiquitin chains during viral infection."

33511009

USP27X affects Histone_H2B

| 3

USP27X deubiquitinates Histone_H2B. 3 / 3

| 3

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"The requirement of ATXN7L3 for H2B deubiquitination by USP22, USP27x, and USP51 suggests that all three use the ATXN7L3 zinc finger to dock the H2A and H2B acidic patch in a manner similar to that shown in the structure of the yeast DUB module bound to ubiquitinated nucleosomes."

27923209

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reach

"Remarkably, this inhibitor also showed greater activity on USP22 than on two other DUBs, USP27x and USP51, that also deubiquitinate histone H2B and form complexes with two of the SAGA DUB module adaptor subunits."

34936860

➶

reach

"Furthermore, USP27X mediates histone H2B deubiquitylation, which is critical for development (Weake et al, 2008)."

38182161

USP27X affects GSK3B

| 2 1

GSK3B binds USP27X. 2 / 2

| 2

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reach

38030604

➶

reach

"For example, glycogen synthase kinase 3 beta (GSK3β) can directly bind to and phosphorylate USP27X, thereby enhancing the interaction between USP27X and CBX2 (Xing et al. 2023)."

39522000

GSK3B binds USP27X. 1 / 1

| 1

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sparser

"Additionally, we have discovered a direct interaction between GSK3β and USP27X, where GSK3β phosphorylates USP27X to enhance its affinity for CBX2 and further stabilize CBX2 protein levels."

38030604

PLEC affects USP27X

| 3

PLEC inhibits USP27X. 3 / 3

| 3

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sparser

"Since hD1 inhibits USP27x whether or not it is in complex with the other SAGA subunits, the inhibitor likely binds directly to the catalytic USP domain."

34936860

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sparser

34936860

➶

sparser

34936860

K48 affects USP27X

| 3

USP27X binds CGAS and K48. 3 / 3

| 3

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reach

"Furthermore, the deubiquitinating enzyme USP27X associates with cGAS and eliminates K48-linked polyubiquitinated chains from cGAS, leading to the stability of cGAS (24)."

40028324

➶

reach

"In this study, we identified that deubiquitinase USP27X could interact with cGAS and cleave K48 linked polyubiquitination chains from cGAS, leading to cGAS stabilization."

31534008

➶

reach

"Unlike USP14, USP27x directly interacts with cGAS and releases the K48 linked polyubiquitin chains during viral infection."

33511009

USP27X affects Ubiquitin

| 2

USP27X inhibits Ubiquitin.

| 1

USP27X inhibits Ubiquitin. 1 / 1

| 1

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reach

"In the past year, two other deubiquitinating enzymes, USP27X and USP1, have been reported to impede ubiquitin mediated degradation of Snail1 in various biological contexts XREF_BIBR, XREF_BIBR."

33391500

USP27X activates Ubiquitin.

| 1

USP27X activates Ubiquitin. 1 / 1

| 1

➶

reach

"The overexpression of DUB ubiquitin-specific protease 27 X-Linked (USP27X) leads to the loss of the CFLAR protein and sensitizes extrinsic apoptosis in melanoma cells."

36551253

USP27X affects USP27X

| 2

USP27X inhibits USP27X.

| 1

USP27X inhibits USP27X-S135A. 1 / 1

| 1

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38030604

USP27X activates USP27X.

| 1

USP27X activates USP27X-S135Q. 1 / 1

| 1

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reach

38030604

USP27X affects USP22

| 2

USP27X binds USP51 and USP22. 1 / 1

| 1

➶

sparser

27132940

USP27X binds USP22. 1 / 1

| 1

➶

sparser

"All these results indicate that USP27X and the close homologue USP22 specifically interact and stabilize Snail1."

30341066

USP27X affects USP

| 2

USP27X binds USP. 1 / 1

| 1

➶

sparser

"Additionally, our findings suggest that Ser135 may be phosphorylated by GSK3β as it binds to the USP structural domain of USP27X (Supplementary Fig. xref )."

38030604

ATXN7L3 binds ENY2, USP, USP27X, and USP51. 1 / 1

| 1

➶

sparser

"A recent study showed that ATXN7L3 and ENY2 can also form complexes with two additional USP DUBs, USP27x and USP51, and target them to H2B-Ub [ xref ]."

27923209

USP27X affects ITCH

1 | 1

USP27X binds ITCH. 1 / 2

1 | 1

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sparser

"Although we did not detect binding between Usp27x L and CHIP by co-IP, there was a clear interaction of Usp27x L with Itch and also (although less pronounced) with DTX1 (Supplementary Fig. S6B)."

35044632

USP27X affects Histone

| 2

USP27X deubiquitinates Histone. 2 / 2

| 2

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reach

"Interestingly, our previous studies demonstrated that USP27X is inactive in insolation and cannot deubiquitinate histones or digest artificial substrates (such as Ub-AMC) in vitro unless bound by ATXN7L3 (23)."

36001804

➶

reach

"Our previous work uncovered USP27X as an epigenetic modifier that deubiquitinates histone 2B (H2Bub1) and regulates gene transcription (23)."

36001804

USP27X affects H2Bub1

| 2

USP27X deubiquitinates H2Bub1. 2 / 2

| 2

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reach

"Our previous work uncovered USP27X as an epigenetic modifier that deubiquitinates histone 2B (H2Bub1) and regulates gene transcription (23)."

36001804

➶

reach

"USP22, USP27X, or USP51 require ATXN7L3 and ENY2 for their full activity and are unable to deubiquitinate H2Bub1 alone."

35806465

USP27X affects Deubiquitinase

| 2

USP27X activates Deubiquitinase. 2 / 2

| 2

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reach

"The overexpression of DUB ubiquitin-specific protease 27 X-Linked (USP27X) leads to the loss of the CFLAR protein and sensitizes extrinsic apoptosis in melanoma cells."

36551253

➶

reach

"Knockouts of additional members of the SAGA DUB modules, ATXN7L3 and ENY2, or potential USP22 replacements in the DUB module USP27X or USP51 , also did not improve reprogramming efficiency."

40102626

USP affects USP27X

| 2

USP27X binds USP. 1 / 1

| 1

➶

sparser

"Additionally, our findings suggest that Ser135 may be phosphorylated by GSK3β as it binds to the USP structural domain of USP27X (Supplementary Fig. xref )."

38030604

ATXN7L3 binds ENY2, USP, USP27X, and USP51. 1 / 1

| 1

➶

sparser

"A recent study showed that ATXN7L3 and ENY2 can also form complexes with two additional USP DUBs, USP27x and USP51, and target them to H2B-Ub [ xref ]."

27923209

SETD3 affects USP27X

| 2

SETD3 inhibits USP27X.

| 1

SETD3 inhibits USP27X. 1 / 1

| 1

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reach

"Similarly, the decreased proliferation was also confirmed by Ki67 immunofluorescence staining as the proportions of Ki67-positive proliferating cells were significantly lower in USP27 or SETD3 knockdown cells, while SETD3 overexpression could increase Ki67-positive proliferating cells in USP27-deficient cells (Supplementary Fig. S2)."

35018513

SETD3 binds USP27X.

| 1

SETD3 binds USP27X. 1 / 1

| 1

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reach

35018513

PIM2 affects USP27X

| 2

PIM2 phosphorylates USP27X. 2 / 2

| 2

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"PIM2 phosphorylates USP27X, and promotes its deubiquitylation activity for MYC, which promotes its protein stability and leads to increase HK2-mediated aerobic glycolysis in breast cancer."

38969771

➶

reach

"Phosphorylation of USP27X by PIM2 promotes glycolysis and breast cancer progression via deubiquitylation of MYC."

38969771

ITCH affects USP27X

1 | 1

USP27X binds ITCH. 1 / 2

1 | 1

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"Although we did not detect binding between Usp27x L and CHIP by co-IP, there was a clear interaction of Usp27x L with Itch and also (although less pronounced) with DTX1 (Supplementary Fig. S6B)."

35044632

ENY2 affects ATXN7L3

| 1 1

USP27X binds ENY2 and ATXN7L3. 1 / 1

| 1

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reach

34936860

ATXN7L3 binds ENY2, USP, USP27X, and USP51. 1 / 1

| 1

➶

sparser

"A recent study showed that ATXN7L3 and ENY2 can also form complexes with two additional USP DUBs, USP27x and USP51, and target them to H2B-Ub [ xref ]."

27923209

EGFR inhibitor affects USP27X

| 2

EGFR inhibitor inhibits USP27X.

| 1

EGFR inhibitor inhibits USP27X. 1 / 1

| 1

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reach

"Finally, deletion of Usp27x reduces apoptosis in NSCLC cells treated with an EGFR inhibitor."

27013495

EGFR inhibitor activates USP27X.

| 1

EGFR inhibitor activates USP27X. 1 / 1

| 1

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reach

"In addition, in NSCLC cells, depletion of USP27x reduces apoptosis when treated with an EGFR inhibitor."

28279784

ATXN7L3 affects ENY2

| 1 1

USP27X binds ENY2 and ATXN7L3. 1 / 1

| 1

➶

reach

34936860

ATXN7L3 binds ENY2, USP, USP27X, and USP51. 1 / 1

| 1

➶

sparser

"A recent study showed that ATXN7L3 and ENY2 can also form complexes with two additional USP DUBs, USP27x and USP51, and target them to H2B-Ub [ xref ]."

27923209

AKT affects USP27X

| 2

AKT activates USP27X. 2 / 2

| 2

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"Silencing of AKT eliminated the promoter functions of USP27X‐AS1, including migration and invasion (Figure 6O,P,S,T and Figure S9B,D)."

38279869

➶

reach

"After treating USP27X‐AS1 knockdown or overexpression cells with MG132, AKT protein level only restored in knockdown cell lines, indicating USP27X‐AS1 inhibited AKT proteasome degradation (Figure 5D,E and Figure S5D,E)."

38279869

5-formyluracil affects USP27X

| 2

5-formyluracil inhibits USP27X.

| 1

5-formyluracil inhibits USP27X. 1 / 1

| 1

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reach

"In our study, we found that both USP27 and Cyclin E are downregulated by 5-FU treatment in a dose dependent manner."

29497124

5-formyluracil decreases the amount of USP27X.

| 1

5-formyluracil decreases the amount of USP27X. 1 / 1

| 1

➶

reach

"Anti-cancer drug 5-FU regulates cell cycle progression and inhibits hepatocellular proliferation by downregulating USP27 expression."

29497124

ΒTrCP affects USP27X

| 1

USP27X binds βTrCP. 1 / 1

| 1

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reach

"Interestingly, binding of USP27x and βTrCP to BIM is independent, as knockdown of βTrCP did not reduce the association of BIM with USP27x."

37584295

Superoxide affects USP27X

| 1

Superoxide inhibits USP27X. 1 / 1

| 1

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reach

"Down-regulation of Raptor expression increased mitochondrial ROS production, and mitochondria specific superoxide scavengers prevented USP27x-mediated stabilization of Bim by inhibition of Cat K. Moreover, combined treatment with Cat K inhibitor (odanacatib) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) reduced tumor growth and induced cell death in a xenograft model."

31901727

Proteasome inhibitor affects USP27X

| 1

Proteasome inhibitor activates USP27X. 1 / 1

| 1

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reach

"XREF_FIG, MG132 (proteasome inhibitor) treatment could rescue the USP27 knockdown mediated degradation of Cyclin E protein."

29497124

MiR-214-5p affects USP27X

| 1

MiR-214-5p activates USP27X. 1 / 1

| 1

➶

reach

"In conclusion, our research results show that miR-214-5p promotes the antitumor effect of NK cells by regulating the USP27X/Bim pathway, thereby inhibiting CRC liver metastasis."

39435421

CGAS affects USP27X

| 1

USP27X binds cGAS. 1 / 1

| 1

➶

sparser

"Unlike USP14, USP27x directly interacts with cGAS and releases the K48‐linked polyubiquitin chains during viral infection. [ xref ] Recently, a study reported that USP29 interacts with cGAS, hydrolyzes K48‐linked polyubiquitin chains on cGAS, and stabilizes cGAS in uninfected cells, or after HSV‐1 stimulation. [ xref ] Following HSV‐1 infection, USP29 knockout mice were shown to be hypersensitive to HSV‐1 and produced less type I IFNs and proinflammatory cytokines than the wildtype control."

33511009

XLID105 variants affects USP27X

| 1

XLID105 variants inhibits USP27X. 1 / 1

| 1

➶

reach

"We demonstrated that most XLID105 variants disrupt distinct aspects of USP27X protein biology that could perturb its function."

38182161

XLID105 missense variants affects USP27X

| 1

XLID105 missense variants inhibits USP27X. 1 / 1

| 1

➶

reach

"These data indicate that most of the XLID105 missense variants disrupt USP27X catalytic activity, which may represent a major pathogenic mechanism in this disorder.To further characterize these variants, we used a DUB activity-based probe."

38182161

VSIR affects USP27X

| 1

VSIR inhibits USP27X. 1 / 1

| 1

➶

reach

"We then focused on SP1: qRT‐PCR and Western blot analysis showed that siSP1 decreased USP27X‐AS1 expression, and vice versa (Figure 7E–H and Figure S10A–D)."

38279869

USP51 affects USP22

| 1

USP27X binds USP51 and USP22. 1 / 1

| 1

➶

sparser

27132940

USP51 affects USP

| 1

ATXN7L3 binds ENY2, USP, USP27X, and USP51. 1 / 1

| 1

➶

sparser

"A recent study showed that ATXN7L3 and ENY2 can also form complexes with two additional USP DUBs, USP27x and USP51, and target them to H2B-Ub [ xref ]."

27923209

USP27X affects βTrCP

| 1

USP27X binds βTrCP. 1 / 1

| 1

➶

reach

"Interestingly, binding of USP27x and βTrCP to BIM is independent, as knockdown of βTrCP did not reduce the association of BIM with USP27x."

37584295

USP27X affects ~3

| 1

USP27X inhibits ~3. 1 / 1

| 1

➶

reach

"USP27X-depleted tumors weighed ~3 fold less than control tumors (Supplementary Fig. 4)."

36001804

USP27X affects tumor cell growth

| 1

USP27X activates tumor cell growth. 1 / 1

| 1

➶

eidos

"Here , we reported that ubiquitin-specific peptidase 27 ( USP27 ) promotes tumor cell growth by specifically interacting with SETD3 , negatively regulating its ubiquitination , and enhancing its stability ."

35018513

USP27X affects stabilization Bim

| 1

USP27X activates stabilization Bim. 1 / 1

| 1

➶

eidos

"Weber et al. reported that USP27x induced stabilization of Bim [ 27 ] ."

31817696

USP27X affects signal transduction

| 1

USP27X activates signal transduction. 1 / 1

| 1

➶

reach

"The obtained results conclusively verify that USP27X‐AS1 promotes both cell proliferation and metastasis of HCC in vivo.3.4 USP27X-AS1 regulated the PI3K-AKT signalling pathway."

38279869

USP27X affects proteasome complex disassembly

| 1

USP27X activates proteasome complex disassembly. 1 / 1

| 1

➶

reach

"Taken together, USP27X‐AS1 upregulated AKT signalling via interacting with AKT protein.3.5 USP27X-AS1 inhibited AKT proteasome degradation."

38279869

USP27X affects opening molecules

| 1

USP27X inhibits opening molecules. 1 / 1

| 1

➶

eidos

"Inhibition of USP27X enhanced cell death promoted by exposition to cisplatin [ 5 ] , opening the possibility to use small molecules against this enzyme to restore or potentiate chemosensitivy to cisplatin or other drugs ."

30613357

USP27X affects neurogenesis

| 1

USP27X inhibits neurogenesis. 1 / 1

| 1

➶

reach

"Knockout mice have not been generated; however, overexpression of Usp27x inhibits neurogenesis in mice (44)."

35662507

USP27X affects inflammatory response

| 1

USP27X activates inflammatory response. 1 / 1

| 1

➶

reach

"Hence, USP27X and USP29 promote the production of cGAMP and downstream IFNs to mediate inflammation and autoimmune responses (Guo et al., 2019; Zhang et al., 2020b)."

36579404

USP27X affects fibroblast activation

| 1

USP27X activates fibroblast activation. 1 / 1

| 1

➶

reach

"Depletion of USP27X inhibited TGF-β-induced EMT and fibroblast activation, which is consistent with this [ 71 ]."

36179816

USP27X affects cisplatin

| 1

USP27X activates cisplatin. 1 / 1

| 1

➶

reach

"USP27X depletion impaired Snail1 dependent cell migration and invasion and metastasis formation and increased cellular sensitivity to cisplatin."

30341066

USP27X affects cell tumorigenesis carcinoma

| 1

USP27X activates cell tumorigenesis carcinoma. 1 / 1

| 1

➶

eidos

"Inhibition of USP27 expression led to the downregulation of SETD3 protein level , the blockade of the cell proliferation and tumorigenesis of hepatocellular carcinoma ( HCC ) cells ."

35018513

USP27X affects cell differentiation

| 1

USP27X inhibits cell differentiation. 1 / 1

| 1

➶

reach

"Knockdown of Usp22 shortened the half-life of Hes1, delayed its oscillation, and enhanced neuronal differentiation in mouse developing brain, whereas mis expression of Usp27x reduced neuronal differentiation."

25846153

USP27X affects cell death

| 1

USP27X inhibits cell death. 1 / 1

| 1

➶

reach

"Inhibition of USP27X enhanced cell death promoted by exposition to cisplatin [5], opening the possibility to use small molecules against this enzyme to restore or potentiate chemosensitivy to cisplatin or other drugs.Recently, Dub3 was also described as a deubiquitinase of Snail1 [9]."

30613357

USP27X affects cell death exposition

| 1

USP27X inhibits cell death exposition. 1 / 1

| 1

➶

eidos

30613357

USP27X affects cdk-4

| 1

USP27X increases the amount of cdk-4. 1 / 1

| 1

➶

reach

"Figure 2F confirms that USP27X loss causes a substantial reduction of CCND1, but not CCND3, CCNE1, or CDK4/6 protein levels in these cells."

36001804

USP27X affects cGAS

| 1

USP27X binds cGAS. 1 / 1

| 1

➶

sparser

33511009

USP27X affects USP7

| 1

USP27X decreases the amount of USP7. 1 / 1

| 1

➶

reach

38279869

USP27X affects USP27X-AS1

| 1

USP27X increases the amount of USP27X-AS1. 1 / 1

| 1

➶

reach

"These data proved that USP27X‐AS1 promoted HCC progression via the AKT signalling pathway.3.7 SP1 upregulated USP27X-AS1 transcription."

38279869

USP27X affects TBCEL

| 1

TBCEL binds USP27X. 1 / 1

| 1

➶

sparser

"Furthermore, like βTrCP1/2, the binding of USP27x to BIM EL was dependent upon ERK1/2 activation."

28548464

USP27X affects Snail1

| 1

USP27X deubiquitinates Snail1. 1 / 1

| 1

➶

reach

"USP27X can also deubiquitinate and stabilize Snail1 when induced by TGF-beta and therefore promotes EMT and tumor metastasis [XREF_BIBR]."

33466790

USP27X affects Snail1 protein

| 1

USP27X inhibits Snail1 protein. 1 / 1

| 1

➶

reach

"Accordingly, downregulation of USP27X decreased Snail1 protein in several tumor cell lines."

30341066

USP27X affects SP1

| 1

SP1 binds USP27X. 1 / 1

| 1

➶

reach

"55 , 56 In this study, we confirmed that SP1 binds to the USP27X‐AS1 promoter, activating USP27X‐AS1 transcription and resulting in elevated expression in HCC tissues."

38279869

USP27X affects SNAI1 stability

| 1

USP27X activates SNAI1 stability. 1 / 1

| 1

➶

eidos

"TGFbeta also induces USP27X expression , which increases SNAI1 stability by deubiquitination [ 55 ] ."

| PMC

USP27X affects SETD3 protein

| 1

USP27X activates SETD3 protein. 1 / 1

| 1

➶

eidos

"Inhibition of USP27 expression led to the downregulation of SETD3 protein level , the blockade of the cell proliferation and tumorigenesis of hepatocellular carcinoma ( HCC ) cells ."

35018513

USP27X affects RTL10

| 1

USP27X deubiquitinates RTL10. 1 / 1

| 1

➶

reach

"Moreover, USP27 deubiquitinates and stabilizes the BH3-only protein Bim, subsequently enhancing apoptosis [14]."

35018513

USP27X affects RPTOR

| 1

USP27X inhibits RPTOR. 1 / 1

| 1

➶

reach

"These data indicated that inhibition of Cat K increases Bim stabilization via up-regulation of USP27x expression.3.5 Down-regulation of raptor is a critical role for Bim stabilization in ODN -treated cells."

31901727

USP27X affects RNF168

| 1

USP27X activates RNF168. 1 / 1

| 1

➶

reach

"Interestingly, the DUBs USP26 and USP27 were found to modulate RNF168 mediated protein ubiquitylation at DSB sites, preventing excessive spreading of RAP80-BRCA1, promoting association of BRCA1 with P[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

29499138

USP27X affects RIG-I ubiquitination

| 1

USP27X inhibits RIG-I ubiquitination. 1 / 1

| 1

➶

eidos

"Additionally , ubiquitination assays demonstrated that USP27X reduced RIG-I ubiquitination , specifically the K63-ubiquitin linkage type ."

33530371

USP27X affects RB1

| 1

USP27X leads to the phosphorylation of RB1. 1 / 1

| 1

➶

reach

"As expected, USP27X depletion substantially reduced both CCND1 levels and Rb1 phosphorylation in these cells (Fig. 5E, compare lane 1 to 2)."

36001804

USP27X affects RAF

| 1

USP27X inhibits RAF. 1 / 1

| 1

➶

reach

"Loss of endogenous Usp27x enhances the Bim degrading activity of oncogenic Raf."

27013495

USP27X affects Protease

| 1

USP27X activates Protease. 1 / 1

| 1

➶

reach

"The overexpression of DUB ubiquitin-specific protease 27 X-Linked (USP27X) leads to the loss of the CFLAR protein and sensitizes extrinsic apoptosis in melanoma cells."

36551253

USP27X affects PLK1

| 1

USP27X increases the amount of PLK1. 1 / 1

| 1

➶

reach

"For instance, the USP27-mediated stability of the SETD3 protein promotes PLK1 gene transcription by binding to the promoter, resulting in cell proliferation and migration and HCC tumorigenesis (42, 53)."

38272222

USP27X affects PI3K-AKT

| 1

USP27X activates PI3K-AKT. 1 / 1

| 1

➶

reach

"The obtained results conclusively verify that USP27X‐AS1 promotes both cell proliferation and metastasis of HCC in vivo.3.4 USP27X-AS1 regulated the PI3K-AKT signalling pathway."

38279869

USP27X affects PFKFB3

| 1

USP27X activates PFKFB3. 1 / 1

| 1

➶

reach

"USP27 promotes glycolysis and hepatocellular carcinoma progression by stabilizing PFKFB3 through deubiquitination."

39746496

USP27X affects PCNA

| 1

USP27X activates PCNA. 1 / 1

| 1

➶

reach

"Instead, overexpression of USP27X‐AS1 increased tumour burden, PCNA and liver metastasis nodules (each group n = 7) (Figure 3G–K)."

38279869

USP27X affects Osteosarcoma

| 1

USP27X inhibits Osteosarcoma. 1 / 1

| 1

➶

reach

"Overexpression of the Ubiquitin Specific Proteases USP43, USP41, USP27x and USP6 in Osteosarcoma Cell Lines: Inhibition of Osteosarcoma Tumor Growth and Lung Metastasis Development by the USP Antagonist PR619."

34571917

USP27X affects N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal

| 1

USP27X inhibits N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal. 1 / 1

| 1

➶

reach

38279869

USP27X affects Mice

| 1

USP27X inhibits Mice. 1 / 1

| 1

➶

reach

"Knockout mice have not been generated; however, overexpression of Usp27x inhibits neurogenesis in mice (44)."

35662507

USP27X affects Interferon

| 1

USP27X activates Interferon. 1 / 1

| 1

➶

reach

"Among the DUBs that interact with cGAS or MDA5, USP27X (98) and USP29 (99) stabilize cGAS and thus positively regulate IFN production and antiviral activities."

34707613

USP27X affects IFNs

| 1

USP27X activates IFNs. 1 / 1

| 1

➶

reach

"Hence, USP27X and USP29 promote the production of cGAMP and downstream IFNs to mediate inflammation and autoimmune responses (Guo et al., 2019; Zhang et al., 2020b)."

36579404

USP27X affects IFNB1

| 1

USP27X activates IFNB1. 1 / 1

| 1

➶

reach

"Additionally, the activation of USP27X induces cGAMP-dependent production of IFN-β in response to cytosolic DNA [102]."

38675916

USP27X affects HLF

| 1

USP27X activates HLF. 1 / 1

| 1

➶

reach

38279869

USP27X affects H2Aub1

| 1

USP27X deubiquitinates H2Aub1. 1 / 1

| 1

➶

reach

"As was previously shown for the USP22 DUBm, both USP27X and USP51 DUBm also deubiquitinated nucleosomal or free H2Aub1 (XREF_FIG and XREF_SUPPLEMENTARY)."

27132940

USP27X affects Guo

| 1

USP27X activates Guo. 1 / 1

| 1

➶

reach

"Hence, USP27X and USP29 promote the production of cGAMP and downstream IFNs to mediate inflammation and autoimmune responses (Guo et al., 2019; Zhang et al., 2020b)."

36579404

USP27X affects ERK

| 1

USP27X binds ERK and BCL2L11. 1 / 1

| 1

➶

sparser

"Here, we report the identification of a deubiquitinase, Usp27x, that binds Bim upon its ERK-dependent phosphorylation and can upregulate its expression levels."

27013495

USP27X affects E3-ligase tripartite motif containing 28

| 1

USP27X binds E3-ligase tripartite motif containing 28. 1 / 1

| 1

➶

reach

"USP27X interacts with the E3-ligase tripartite motif containing 28 (TRIM28) and reduces the ubiquitination of E3-ligases TRIM28, but not ITCH and DTX1, which leads to decreased CFLAR protein [17]."

36551253

USP27X affects Cell Survival

| 1

USP27X activates Cell Survival. 1 / 1

| 1

➶

reach

"As shown in Fig. 4A and B, USP27 knockdown markedly reduce the cell viability of Hep3B and MHCC97H cells."

35018513

USP27X affects Caspase

| 1

USP27X activates Caspase. 1 / 1

| 1

➶

reach

"Overexpression of USP27x combined with ERK1/2 activation to promote the deubiquitylation and stabilisation of BIM and increase caspase‐dependent apoptosis."

28548464

USP27X affects Carcinoma, Hepatocellular

| 1

USP27X activates Carcinoma, Hepatocellular. 1 / 1

| 1

➶

reach

"USP27 promotes glycolysis and hepatocellular carcinoma progression by stabilizing PFKFB3 through deubiquitination."

39746496

USP27X affects CFLAR

| 1

USP27X decreases the amount of CFLAR. 1 / 1

| 1

➶

reach

"Here, we report that enhanced expression of Usp27x in human melanoma cells leads to the loss of cellular FLICE-like inhibitory protein (cFLIP) and sensitizes to Tumor necrosis factor receptor 1 (TNF-R1) or Toll-like receptor 3 (TLR3)-induced extrinsic apoptosis through enabling enhanced processing of caspase-8."

35044632

USP27X affects BTRC

| 1

USP27X binds BTRC. 1 / 1

| 1

➶

sparser

"IκBα-degradation is achieved through the activity of the E3-ubiquitin ligase complex SCF β-TRCP [ xref ], and it has been reported that Usp27x can bind β-TrCP [ xref , xref ]."

35044632

USP27X affects BC

| 1

USP27X activates BC. 1 / 1

| 1

➶

reach

"Our findings suggest that USP27X promotes BC progression through CBX2."

38030604

USP22 affects USP51

| 1

USP27X binds USP51 and USP22. 1 / 1

| 1

➶

sparser

27132940

USP affects USP51

| 1

ATXN7L3 binds ENY2, USP, USP27X, and USP51. 1 / 1

| 1

➶

sparser

"A recent study showed that ATXN7L3 and ENY2 can also form complexes with two additional USP DUBs, USP27x and USP51, and target them to H2B-Ub [ xref ]."

27923209

TBCEL affects USP27X

| 1

TBCEL binds USP27X. 1 / 1

| 1

➶

sparser

"Furthermore, like βTrCP1/2, the binding of USP27x to BIM EL was dependent upon ERK1/2 activation."

28548464

SP1.4 DISCUSSION affects USP27X

| 1

SP1.4 DISCUSSION increases the amount of USP27X. 1 / 1

| 1

➶

reach

"Thus, binding sites 1, 2 and 3 were deemed critical to activating USP27X‐AS1 transcription by SP1.4 DISCUSSION."

38279869

SP1 affects USP27X

| 1

SP1 binds USP27X. 1 / 1

| 1

➶

reach

"55 , 56 In this study, we confirmed that SP1 binds to the USP27X‐AS1 promoter, activating USP27X‐AS1 transcription and resulting in elevated expression in HCC tissues."

38279869

SNAI1 affects USP27X

| 1

SNAI1 binds USP27X. 1 / 1

| 1

➶

reach

"In TNBC, but not in HER2-positive tumors, there is a significant association between Snail1 and USP27X."

36179816

Reactive Oxygen Species affects USP27X

| 1

Reactive Oxygen Species increases the amount of USP27X. 1 / 1

| 1

➶

reach

"Furthermore, ODN-mediated mitochondrial ROS production induced USP27x expression."

31901727

RPTOR affects USP27X

| 1

RPTOR increases the amount of USP27X. 1 / 1

| 1

➶

reach

"In addition, overexpression of Raptor and blockers of mitochondrial ROS blocked ODN-induced USP27x expression (Fig. 6L and M)."

31901727

MiR-214-5p affects USP27X

| 1

MiR-214-5p activates USP27X. 1 / 1

| 1

➶

reach

"MiR-214-5p promotes the anti-tumor activity of NK cells by regulating the USP27X/Bim pathway, thereby inhibiting colorectal cancer (CRC) liver metastasis [35]."

40098140

HYCC1 affects USP27X

| 1

HYCC1 activates USP27X. 1 / 1

| 1

➶

reach

"All these results confirmed the HCC‐promoting ability of USP27X‐AS1.3.3 USP27X-AS1 promoted HCC progression in vivo."

38279869

ERK affects USP27X

| 1

USP27X binds ERK and BCL2L11. 1 / 1

| 1

➶

sparser

"Here, we report the identification of a deubiquitinase, Usp27x, that binds Bim upon its ERK-dependent phosphorylation and can upregulate its expression levels."

27013495

ENY2 affects USP51

| 1

ATXN7L3 binds ENY2, USP, USP27X, and USP51. 1 / 1

| 1

➶

sparser

"A recent study showed that ATXN7L3 and ENY2 can also form complexes with two additional USP DUBs, USP27x and USP51, and target them to H2B-Ub [ xref ]."

27923209

E3-ligase tripartite motif containing 28 affects USP27X

| 1

USP27X binds E3-ligase tripartite motif containing 28. 1 / 1

| 1

➶

reach

"USP27X interacts with the E3-ligase tripartite motif containing 28 (TRIM28) and reduces the ubiquitination of E3-ligases TRIM28, but not ITCH and DTX1, which leads to decreased CFLAR protein [17]."

36551253

Dbi affects USP27X

| 1

Dbi increases the amount of USP27X. 1 / 1

| 1

➶

sparser

"In addition, overexpression of Raptor and blockers of mitochondrial ROS blocked ODN-induced USP27x expression ( xref L and M)."

31901727

CAT affects USP27X

| 1

CAT increases the amount of USP27X. 1 / 1

| 1

➶

reach

"However, ODN only increased USP27x expression within 3 h (Fig. 4D), and KD or KO of Cat K also induced USP27x expression (Fig. 4E and F)."

31901727

BTRC affects USP27X

| 1

USP27X binds BTRC. 1 / 1

| 1

➶

sparser

"IκBα-degradation is achieved through the activity of the E3-ubiquitin ligase complex SCF β-TRCP [ xref ], and it has been reported that Usp27x can bind β-TrCP [ xref , xref ]."

35044632

BCL2L11 affects ERK, and USP27X

| 1

USP27X binds ERK and BCL2L11. 1 / 1

| 1

➶

sparser

"Here, we report the identification of a deubiquitinase, Usp27x, that binds Bim upon its ERK-dependent phosphorylation and can upregulate its expression levels."

27013495

AuGCT affects USP27X

| 1

AuGCT activates USP27X. 1 / 1

| 1

➶

reach

"AuGCT (AuGCT DNA‐SYN Biotechnology Co., Ltd) produced the full‐length human USP27X‐AS1 cDNA (2304 bp), which was then cloned into the expression vector pcDNA3.1(+) from Add‐gene."

38279869

ATXN7L3 affects USP51

| 1

ATXN7L3 binds ENY2, USP, USP27X, and USP51. 1 / 1

| 1

➶

sparser

"A recent study showed that ATXN7L3 and ENY2 can also form complexes with two additional USP DUBs, USP27x and USP51, and target them to H2B-Ub [ xref ]."

27923209

ATXN7L3 affects ENY2, and USP27X

| 1

USP27X binds ENY2 and ATXN7L3. 1 / 1

| 1

➶

reach

34936860

ATXN7L3 affects ENY2, USP, USP27X, and USP51

| 1

ATXN7L3 binds ENY2, USP, USP27X, and USP51. 1 / 1

| 1

➶

sparser

"A recent study showed that ATXN7L3 and ENY2 can also form complexes with two additional USP DUBs, USP27x and USP51, and target them to H2B-Ub [ xref ]."

27923209

5-fluorouracil affects USP27X

| 1

5-fluorouracil decreases the amount of USP27X. 1 / 1

| 1

➶

reach

"Treatment with 5-fluorouracil (5-FU) decreases USP27x expression, and then induces degradation of cyclin E [56]."

31901727