IndraLab
Statements
sparser
"Recent studies showed that USP28 was involved in cancer-related pathways, and regulated physiological homeostasis of ubiquitination process, DNA-damage response, and cell cycle during genotoxic stress, which suggested that USP28 could be a promising target for cancer therapy. xref USP28 required for Myc function was screened. xref USP28 bound to Myc through an interaction with Fbw7α, and catalyzed the deubiquitination of Myc, thereby promoting its stabilization and contributing to tumor cell growth in colon and breast cancers. xref , xref USP28 can also bind to and deubiquitinate some proteins involved in DNA-damage pathways."
reach
"In a previous study, circFBXW7 was found to be downregulated in glioma, where it is translated into a 185-amino acid (aa) protein (FBXW7-185aa) that competitively interacts with the deubiquitinating enzyme USP28, preventing USP28 from binding to FBXW7 and antagonizing USP28 induced c-Myc stabilization."
USP28 is modified
3
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2
61
USP28 is phosphorylated.
3
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30
sparser
"The findings that support this conclusion are the following: (i) the binding of UCK1 to the E3 ligase KLHL2 causes its polyubiquitination at K81 and degradation; (ii) the DUB USP28 binds to UCK1 through interaction with KLHL2 and antagonizes KLHL2-mediated effect on UCK1; (iii) UCK1 deubiquitination by USP28 is dependent on the phosphorylation status of USP28; (iv) USP28 is phosphorylated by 5'-AZA-activated ATM, resulting in disassociation of KLHL2 from USP28 and UCK1 destabilization; (v) ATM also phosphorylates UCK1 at S145, significantly enhancing the KLHL2-UCK1 complex formation; (vi) the knockdown of KLHL2 not only significantly inhibits AML cell proliferation, but also sensitizes AML cells to 5'-AZA-induced apoptosis; and (vii) combinational therapies with 5'-AZA and ectopic USP28 expression enhances the effects of 5'-AZA and induces synergistic lethality at cellular level and in the AML mouse model, which is, however, observed in cells deficient in USP28."
sparser
"The USP25 activity may not be affected upon exposure to an inhibitor blocking the phosphorylation of USP28 on serine 67 and serine It could be another therapeutic option to target the binding between ATM and USP28 and reduce the phosphorylation of USP28, thus decreasing its enzymatic activity in cancer cells with increased DNA damage levels."
| PMC
sparser
"The USP25 activity may not be affected upon exposure to an inhibitor blocking the phosphorylation of USP28 on serine 67 and serine It could be another therapeutic option to target the binding between ATM and USP28 and reduce the phosphorylation of USP28, thus decreasing its enzymatic activity in cancer cells with increased DNA damage levels."
| PMC
USP28 is sumoylated.
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18
sparser
"293T cells were co-transfected with HIF-1α, HRE-driven luciferase with renilla as an internal control, and Flag-tagged vector control, Flag-tagged USP28 WT or Flag-tagged USP28 K99R. Our co-transfection data found that the highest HIF-1α luciferase activity was achieved in USP28 K99R transfection group (Fig. xref b), suggesting that USP28 SUMOylation regulates the transcriptional activity of HIF-1α."
USP28 is desumoylated.
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12
USP28 is ubiquitinated.
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1
USP28 is methylated.
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1
USP28 is produced.
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1
reach
"Moreover, upregulated TET1 directly demethylates USP28 promoter, thereby enhancing USP28 transcription and expression, which binds to CD44s protein, and remove the ubiquitin group from the ubiquitinated CD44s protein, resulting in stabilization of CD44s protein to mediate stem like property of human BC cells."
sparser
"While much remains to be learned about how the mitotic surveillance pathway functions to survey centrosomes, a plausible model is that in response to centrosome loss, 53BP1 binds to USP28 and p53 to facilitate USP28-dependent deubiquitination and activation of p53, leading to cell cycle arrest xref , xref ( xref )."
sparser
"Strikingly, unlike unstressedp21 -/- cells that mostly lacked nuclear p53, in the stressed condition, p53 not only was stabilized in the nucleus, but also formed bright nuclear foci of various sizes co-localizing with 53BP1 and USP28 in ~30% of the cell population ( xref ), suggesting that 53BP1, USP28 and p53 interact with each other after a stressed mitosis, consistent with the known interaction between 53BP1 and p53 or USP28 ( xref ; xref ; xref )."
sparser
"Several mechanisms of intrinsic resistance have been described among whom loss of PTEN, cyclin D1 amplification, loss of NF1, RAC1 P29S mutation, HGF secretion, MAP3K8 overexpression, loss of the USP28–FBW7 complex, low levels of CD8 tumor-infiltrating T cells and increased expression of the immune inhibitory molecule PD-L1 ( xref – xref )."
reach
"Other proteins regulating C-MYC stability include : CIP2A, a C-MYC-interacting protein that specifically inhibits PP2A activity against C-MYC; USP28, a de-ubiquitinating enzymes that antagonizes FBW7 and promotes C-MYC stability and TRUSS, a receptor for DDB1 (damage specific DNA binding protein 1)-CUL4 (Cullin 4) E3 ligase complex."
reach
"A study has proposed a novel mechanism by which USP28 upregulates angiogenesis by antagonizing GSK-3beta (glycogen synthase kinase-3beta) and FBW7 dependent degradation of HIF-1alpha (hypoxia inducible factor-1alpha), a major regulator of angiogenesis, carcinogenesis, and various processes by which cells adapt to hypoxic conditions."
sparser
"Recent studies showed that USP28 was involved in cancer-related pathways, and regulated physiological homeostasis of ubiquitination process, DNA-damage response, and cell cycle during genotoxic stress, which suggested that USP28 could be a promising target for cancer therapy. xref USP28 required for Myc function was screened. xref USP28 bound to Myc through an interaction with Fbw7α, and catalyzed the deubiquitination of Myc, thereby promoting its stabilization and contributing to tumor cell growth in colon and breast cancers. xref , xref USP28 can also bind to and deubiquitinate some proteins involved in DNA-damage pathways."
reach
"While much remains to be learned about how the mitotic surveillance pathway functions to survey centrosomes, a plausible model is that in response to centrosome loss, 53BP1 binds to USP28 and p53 to facilitate USP28 dependent deubiquitination and activation of p53, leading to cell cycle arrest XREF_BIBR, XREF_BIBR (XREF_FIG)."
reach
"For example, the DNA damage response pathway is central to the maintenance of genomic stability and both members of a key DDR complex, the TP53BP1 and USP28 complex, which are substrates of the ATM kinase, were identified within the top 110 TSGs (q-value < 0.15, XREF_FIG, XREF_FIG)."
sparser
"While much remains to be learned about how the mitotic surveillance pathway functions to survey centrosomes, a plausible model is that in response to centrosome loss, 53BP1 binds to USP28 and p53 to facilitate USP28-dependent deubiquitination and activation of p53, leading to cell cycle arrest xref , xref ( xref )."
sparser
"Strikingly, unlike unstressedp21 -/- cells that mostly lacked nuclear p53, in the stressed condition, p53 not only was stabilized in the nucleus, but also formed bright nuclear foci of various sizes co-localizing with 53BP1 and USP28 in ~30% of the cell population ( xref ), suggesting that 53BP1, USP28 and p53 interact with each other after a stressed mitosis, consistent with the known interaction between 53BP1 and p53 or USP28 ( xref ; xref ; xref )."
reach
"While much remains to be learned about how the mitotic surveillance pathway functions to survey centrosomes, a plausible model is that in response to centrosome loss, 53BP1 binds to USP28 and p53 to facilitate USP28 dependent deubiquitination and activation of p53, leading to cell cycle arrest XREF_BIBR, XREF_BIBR (XREF_FIG)."
reach
"For example, the DNA damage response pathway is central to the maintenance of genomic stability and both members of a key DDR complex, the TP53BP1 and USP28 complex, which are substrates of the ATM kinase, were identified within the top 110 TSGs (q-value < 0.15, XREF_FIG, XREF_FIG)."
sparser
"While much remains to be learned about how the mitotic surveillance pathway functions to survey centrosomes, a plausible model is that in response to centrosome loss, 53BP1 binds to USP28 and p53 to facilitate USP28-dependent deubiquitination and activation of p53, leading to cell cycle arrest xref , xref ( xref )."
sparser
"Strikingly, unlike unstressedp21 -/- cells that mostly lacked nuclear p53, in the stressed condition, p53 not only was stabilized in the nucleus, but also formed bright nuclear foci of various sizes co-localizing with 53BP1 and USP28 in ~30% of the cell population ( xref ), suggesting that 53BP1, USP28 and p53 interact with each other after a stressed mitosis, consistent with the known interaction between 53BP1 and p53 or USP28 ( xref ; xref ; xref )."
reach
"To examine whether interaction of HDAC5 with LSD1 and USP28 complex deacetylates LSD1 or USP28, in vitro protein acetylation assays was first carried out by incubating GST tagged recombinant HDAC5 protein with cellular pull-down of LSD1-FLAG or USP28-FLAG by IP, and immunoprecipitates of IgG was incubated with recombinant HDAC5 protein as negative control of assays (XREF_FIG)."
reach
"To understand whether HDAC5 may stabilize LSD1 protein through upregulation of USP28 protein stability, a rescue study was carried out in MDA-MB-231 and MCF10A-CA1a cells using concurrent transfection of HDAC5 siRNA and USP28 expression plasmids, and showed that overexpression of USP28 completely blocked the destabilization of LSD1 by HDAC5 depletion (XREF_FIG, XREF_SUPPLEMENTARY)."
USP28 affects cell population proliferation
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1
30
USP28 activates cell population proliferation.
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1
23
USP28 inhibits cell population proliferation.
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7
sparser
"Several mechanisms of intrinsic resistance have been described among whom loss of PTEN, cyclin D1 amplification, loss of NF1, RAC1 P29S mutation, HGF secretion, MAP3K8 overexpression, loss of the USP28–FBW7 complex, low levels of CD8 tumor-infiltrating T cells and increased expression of the immune inhibitory molecule PD-L1 ( xref – xref )."
sparser
"While much remains to be learned about how the mitotic surveillance pathway functions to survey centrosomes, a plausible model is that in response to centrosome loss, 53BP1 binds to USP28 and p53 to facilitate USP28-dependent deubiquitination and activation of p53, leading to cell cycle arrest xref , xref ( xref )."
sparser
"Strikingly, unlike unstressedp21 -/- cells that mostly lacked nuclear p53, in the stressed condition, p53 not only was stabilized in the nucleus, but also formed bright nuclear foci of various sizes co-localizing with 53BP1 and USP28 in ~30% of the cell population ( xref ), suggesting that 53BP1, USP28 and p53 interact with each other after a stressed mitosis, consistent with the known interaction between 53BP1 and p53 or USP28 ( xref ; xref ; xref )."
reach
"To examine whether interaction of HDAC5 with LSD1 and USP28 complex deacetylates LSD1 or USP28, in vitro protein acetylation assays was first carried out by incubating GST tagged recombinant HDAC5 protein with cellular pull-down of LSD1-FLAG or USP28-FLAG by IP, and immunoprecipitates of IgG was incubated with recombinant HDAC5 protein as negative control of assays (XREF_FIG)."
reach
"The findings that support this conclusion are the following : (i) the binding of UCK1 to the E3 ligase KLHL2 causes its polyubiquitination at K81 and degradation; (ii) the DUB USP28 binds to UCK1 through interaction with KLHL2 and antagonizes KLHL2 mediated effect on UCK1; (iii) UCK1 deubiquitination by USP28 is dependent on the phosphorylation status of USP28; (iv) USP28 is phosphorylated by 5 '-AZA-activated ATM, resulting in disassociation of KLHL2 from USP28 and UCK1 destabilization; (v) ATM also phosphorylates UCK1 at S145, significantly enhancing the KLHL2 and UCK1 complex formation; (vi) the knockdown of KLHL2 not only significantly inhibits AML cell proliferation, but also sensitizes AML cells to 5 '-AZA-induced apoptosis; and (vii) combinational therapies with 5 '-AZA and ectopic USP28 expression enhances the effects of 5 '-AZA and induces synergistic lethality at cellular level and in the AML mouse model, which is, however, observed in cells deficient in USP28."
sparser
"The findings that support this conclusion are the following: (i) the binding of UCK1 to the E3 ligase KLHL2 causes its polyubiquitination at K81 and degradation; (ii) the DUB USP28 binds to UCK1 through interaction with KLHL2 and antagonizes KLHL2-mediated effect on UCK1; (iii) UCK1 deubiquitination by USP28 is dependent on the phosphorylation status of USP28; (iv) USP28 is phosphorylated by 5'-AZA-activated ATM, resulting in disassociation of KLHL2 from USP28 and UCK1 destabilization; (v) ATM also phosphorylates UCK1 at S145, significantly enhancing the KLHL2-UCK1 complex formation; (vi) the knockdown of KLHL2 not only significantly inhibits AML cell proliferation, but also sensitizes AML cells to 5'-AZA-induced apoptosis; and (vii) combinational therapies with 5'-AZA and ectopic USP28 expression enhances the effects of 5'-AZA and induces synergistic lethality at cellular level and in the AML mouse model, which is, however, observed in cells deficient in USP28."
USP28 binds UCK1 and Hemagglutinins. 1 / 1
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1
sparser
"Once all the three conservative SQ sites (S67, S495, and S714), in USP28, were mutated to alanine, the pS/TQ antibody completely could not recognize the immunoprecipitated Flag-USP28-3S/A (Figure xref D), suggesting that in response to 5'-AZA-induced stress, ATM phosphorylates USP28 at all these three sites."
reach
"The findings that support this conclusion are the following : (i) the binding of UCK1 to the E3 ligase KLHL2 causes its polyubiquitination at K81 and degradation; (ii) the DUB USP28 binds to UCK1 through interaction with KLHL2 and antagonizes KLHL2 mediated effect on UCK1; (iii) UCK1 deubiquitination by USP28 is dependent on the phosphorylation status of USP28; (iv) USP28 is phosphorylated by 5 '-AZA-activated ATM, resulting in disassociation of KLHL2 from USP28 and UCK1 destabilization; (v) ATM also phosphorylates UCK1 at S145, significantly enhancing the KLHL2 and UCK1 complex formation; (vi) the knockdown of KLHL2 not only significantly inhibits AML cell proliferation, but also sensitizes AML cells to 5 '-AZA-induced apoptosis; and (vii) combinational therapies with 5 '-AZA and ectopic USP28 expression enhances the effects of 5 '-AZA and induces synergistic lethality at cellular level and in the AML mouse model, which is, however, observed in cells deficient in USP28."
sparser
"The findings that support this conclusion are the following: (i) the binding of UCK1 to the E3 ligase KLHL2 causes its polyubiquitination at K81 and degradation; (ii) the DUB USP28 binds to UCK1 through interaction with KLHL2 and antagonizes KLHL2-mediated effect on UCK1; (iii) UCK1 deubiquitination by USP28 is dependent on the phosphorylation status of USP28; (iv) USP28 is phosphorylated by 5'-AZA-activated ATM, resulting in disassociation of KLHL2 from USP28 and UCK1 destabilization; (v) ATM also phosphorylates UCK1 at S145, significantly enhancing the KLHL2-UCK1 complex formation; (vi) the knockdown of KLHL2 not only significantly inhibits AML cell proliferation, but also sensitizes AML cells to 5'-AZA-induced apoptosis; and (vii) combinational therapies with 5'-AZA and ectopic USP28 expression enhances the effects of 5'-AZA and induces synergistic lethality at cellular level and in the AML mouse model, which is, however, observed in cells deficient in USP28."
USP28 binds UCK1 and Hemagglutinins. 1 / 1
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1
USP28 affects cell growth
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12
1
USP28 activates cell growth.
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8
USP28 inhibits cell growth.
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4
1
MiR-3940-5p affects USP28
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12
MiR-3940-5p inhibits USP28.
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5
MiR-3940-5p activates USP28.
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5
MiR-3940-5p decreases the amount of USP28.
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2
USP28 affects apoptotic process
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12
USP28 activates apoptotic process.
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9
USP28 inhibits apoptotic process.
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3
reach
"Importantly, of the 59 patients harboring BRAF V600E mutations 27% (16/59) displayed a> 50% decrease in USP28 mRNA expression levels, suggesting that in tumors harboring BRAF alterations, loss of USP28 may further increase the tumorigenic potential of these tumors by stabilizing BRAF and enhancing downstream MAPK activation."
sparser
"While much remains to be learned about how the mitotic surveillance pathway functions to survey centrosomes, a plausible model is that in response to centrosome loss, 53BP1 binds to USP28 and p53 to facilitate USP28-dependent deubiquitination and activation of p53, leading to cell cycle arrest xref , xref ( xref )."
sparser
"Strikingly, unlike unstressedp21 -/- cells that mostly lacked nuclear p53, in the stressed condition, p53 not only was stabilized in the nucleus, but also formed bright nuclear foci of various sizes co-localizing with 53BP1 and USP28 in ~30% of the cell population ( xref ), suggesting that 53BP1, USP28 and p53 interact with each other after a stressed mitosis, consistent with the known interaction between 53BP1 and p53 or USP28 ( xref ; xref ; xref )."
USP28 affects cell cycle
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9
USP28 activates cell cycle.
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7
USP28 activates cell cycle. 7 / 7
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7
reach
"Similarly, western blot analyses revealed that the total p53 levels in 53BP1 -/- or USP28 -/- cells were kept low during acentrosomal cell division in the presence of mitotic delay (XREF_FIG), indicating that 53BP1 and USP28 function upstream of p53 to initiate cell cycle arrest in response to centrosome loss."
USP28 inhibits cell cycle.
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2
reach
"A study has proposed a novel mechanism by which USP28 upregulates angiogenesis by antagonizing GSK-3beta (glycogen synthase kinase-3beta) and FBW7 dependent degradation of HIF-1alpha (hypoxia inducible factor-1alpha), a major regulator of angiogenesis, carcinogenesis, and various processes by which cells adapt to hypoxic conditions."
sparser
"While much remains to be learned about how the mitotic surveillance pathway functions to survey centrosomes, a plausible model is that in response to centrosome loss, 53BP1 binds to USP28 and p53 to facilitate USP28-dependent deubiquitination and activation of p53, leading to cell cycle arrest xref , xref ( xref )."
sparser
"Strikingly, unlike unstressedp21 -/- cells that mostly lacked nuclear p53, in the stressed condition, p53 not only was stabilized in the nucleus, but also formed bright nuclear foci of various sizes co-localizing with 53BP1 and USP28 in ~30% of the cell population ( xref ), suggesting that 53BP1, USP28 and p53 interact with each other after a stressed mitosis, consistent with the known interaction between 53BP1 and p53 or USP28 ( xref ; xref ; xref )."
∆NP63 affects USP28
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7
sparser
"To investigate a therapeutic potential of targeting the USP28‐∆Np63 axis in SCC cells of different origins, we used a set of human cancer cell lines, comprising the pancreas lines PANC‐1 (ADC) and BXPC‐3 (SCC); cervical cancer cell lines HeLa (ADC), SiHa and Ca Ski (SCC); the head‐and‐neck cell line Detroit 562 (SCC); and the lung cell lines H1299 (ADC) and LUDLU‐1 adh (SCC)."
Valproic acid affects USP28
7
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Valproic acid increases the amount of USP28.
6
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Valproic acid increases the amount of USP28. 6 / 6
6
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Valproic acid methylates USP28.
1
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USP28 affects ∆NP63
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7
sparser
"To investigate a therapeutic potential of targeting the USP28‐∆Np63 axis in SCC cells of different origins, we used a set of human cancer cell lines, comprising the pancreas lines PANC‐1 (ADC) and BXPC‐3 (SCC); cervical cancer cell lines HeLa (ADC), SiHa and Ca Ski (SCC); the head‐and‐neck cell line Detroit 562 (SCC); and the lung cell lines H1299 (ADC) and LUDLU‐1 adh (SCC)."
USP28 affects miR-3940-5p
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7
reach
"In combination with a significant negative correlation between expressions of miR-3940-5p versus CCND1 mRNA and USP28 mRNA in NSCLC tissues, these results suggest that CCND1 and USP28 are functional targets of miR-3940-5p and miR-3940-5p affects proliferation and apoptosis in A549 cells by targeting CCND1 and USP28."
USP28 affects angiogenesis
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7
USP28 activates angiogenesis.
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6
USP28 activates angiogenesis. 6 / 6
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6
reach
"A study has proposed a novel mechanism by which USP28 upregulates angiogenesis by antagonizing GSK-3β (glycogen synthase kinase-3β) and FBW7-dependent degradation of HIF-1α (hypoxia-inducible factor-1α), a major regulator of angiogenesis, carcinogenesis, and various processes by which cells adapt to hypoxic conditions."
reach
"USP28 also upregulates angiogenesis by antagonizing GSK-3β (glycogen synthase kinase-3β) and FBW7-dependent degradation of HIF-1α (hypoxia-inducible factor-1α), a major regulator of angiogenesis, carcinogenesis, and various processes by which the cell adapts to hypoxic conditions."
reach
"A study has proposed a novel mechanism by which USP28 upregulates angiogenesis by antagonizing GSK-3beta (glycogen synthase kinase-3beta) and FBW7 dependent degradation of HIF-1alpha (hypoxia inducible factor-1alpha), a major regulator of angiogenesis, carcinogenesis, and various processes by which cells adapt to hypoxic conditions."
USP28 inhibits angiogenesis.
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1
USP28 inhibits angiogenesis. 1 / 1
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1
reach
"Importantly, of the 59 patients harboring BRAF V600E mutations 27% (16/59) displayed a> 50% decrease in USP28 mRNA expression levels, suggesting that in tumors harboring BRAF alterations, loss of USP28 may further increase the tumorigenic potential of these tumors by stabilizing BRAF and enhancing downstream MAPK activation."
sparser
"Consistent with our data, computational modeling of structures predicted by the ZDOCK and PyMol software showed that Ser145 is the critical amino acid mediating the direct binding of UCK1 to KLHL2 (Figure xref J) while Ser67 phosphorylation disrupts the interaction between USP28 and KLHL2 (Figure xref K)."
sparser
"The findings that support this conclusion are the following: (i) the binding of UCK1 to the E3 ligase KLHL2 causes its polyubiquitination at K81 and degradation; (ii) the DUB USP28 binds to UCK1 through interaction with KLHL2 and antagonizes KLHL2-mediated effect on UCK1; (iii) UCK1 deubiquitination by USP28 is dependent on the phosphorylation status of USP28; (iv) USP28 is phosphorylated by 5'-AZA-activated ATM, resulting in disassociation of KLHL2 from USP28 and UCK1 destabilization; (v) ATM also phosphorylates UCK1 at S145, significantly enhancing the KLHL2-UCK1 complex formation; (vi) the knockdown of KLHL2 not only significantly inhibits AML cell proliferation, but also sensitizes AML cells to 5'-AZA-induced apoptosis; and (vii) combinational therapies with 5'-AZA and ectopic USP28 expression enhances the effects of 5'-AZA and induces synergistic lethality at cellular level and in the AML mouse model, which is, however, observed in cells deficient in USP28."
sparser
"Consistent with our data, computational modeling of structures predicted by the ZDOCK and PyMol software showed that Ser145 is the critical amino acid mediating the direct binding of UCK1 to KLHL2 (Figure xref J) while Ser67 phosphorylation disrupts the interaction between USP28 and KLHL2 (Figure xref K)."
sparser
"The findings that support this conclusion are the following: (i) the binding of UCK1 to the E3 ligase KLHL2 causes its polyubiquitination at K81 and degradation; (ii) the DUB USP28 binds to UCK1 through interaction with KLHL2 and antagonizes KLHL2-mediated effect on UCK1; (iii) UCK1 deubiquitination by USP28 is dependent on the phosphorylation status of USP28; (iv) USP28 is phosphorylated by 5'-AZA-activated ATM, resulting in disassociation of KLHL2 from USP28 and UCK1 destabilization; (v) ATM also phosphorylates UCK1 at S145, significantly enhancing the KLHL2-UCK1 complex formation; (vi) the knockdown of KLHL2 not only significantly inhibits AML cell proliferation, but also sensitizes AML cells to 5'-AZA-induced apoptosis; and (vii) combinational therapies with 5'-AZA and ectopic USP28 expression enhances the effects of 5'-AZA and induces synergistic lethality at cellular level and in the AML mouse model, which is, however, observed in cells deficient in USP28."
reach
"Herein, we found that specific knockdown ATG7 resulted in usp28 promoter hypermethylation as comparison to scramble nonsense transfectants in human BC cells, and increased USP28 expression with 5-aza-2-deoxycytidine treatment, strongly indicating that the promoter hypermethylation was responsible for USP28 transcription downregulation due to ATG7 knockdown."
USP28 affects proteolysis
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6
USP28 activates proteolysis.
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5
USP28 inhibits proteolysis.
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1
USP28 inhibits proteolysis. 1 / 1
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1
reach
"The identification of several DUB inhibitors, including inhibitors of USP28, which regulate various oncogenes (e.g., c-Myc) and USP25, which regulates TRAF (tumor necrosis factor receptor-associated factor) signalling, provide alternative approaches to induce degradation of potential “un-druggable” molecules in cancer.Gerry Melino (University of Cambridge, UK) presented data demonstrating the p53 family protein TAp73, facilitates ubiquitin-dependent degradation of HIF1α, thereby suppressing tumor progression."
reach
"Moreover, upregulated TET1 directly demethylates USP28 promoter, thereby enhancing USP28 transcription and expression, which binds to CD44s protein, and remove the ubiquitin group from the ubiquitinated CD44s protein, resulting in stabilization of CD44s protein to mediate stem like property of human BC cells."
reach
"Collectively, our results strongly demonstrate that ATG7 overexpression mediated TET1 upregulation contributes to usp28 promoter demethylation, thereby increasing USP28 expression, consequently resulting in CD44s protein accumulation, and finally enhancing BC stem sphere formation, invasion, and lung metastatic activity."
reach
"Collectively, our results strongly demonstrate that ATG7 overexpression mediated TET1 upregulation contributes to usp28 promoter demethylation, thereby increasing USP28 expression, consequently resulting in CD44s protein accumulation, and finally enhancing BC stem sphere formation, invasion, and lung metastatic activity."
reach
"Collectively, our results demonstrate that ATG7 autophagic removal of AUF1 promotes tet1 mRNA stabilization, which demethylates usp28 promoter, and in turn resulting in accumulation of CD44s protein, finally promoting cancer stem like properties, invasion and lung metastatic activity of human high invasive BC cells as shown in XREF_FIG."
Nickel(2+) affects USP28
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5
Nickel(2+) decreases the amount of USP28.
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4
Nickel(2+) increases the amount of USP28.
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1
Nickel(2+) increases the amount of USP28. 1 / 1
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1
MiR-4295 affects USP28
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5
reach
"The USP25 activity may not be affected upon exposure to an inhibitor blocking the phosphorylation of USP28 on serine 67 and serine It could be another therapeutic option to target the binding between ATM and USP28 and reduce the phosphorylation of USP28, thus decreasing its enzymatic activity in cancer cells with increased DNA damage levels."
| PMC
reach
"The USP25 activity may not be affected upon exposure to an inhibitor blocking the phosphorylation of USP28 on serine 67 and serine It could be another therapeutic option to target the binding between ATM and USP28 and reduce the phosphorylation of USP28, thus decreasing its enzymatic activity in cancer cells with increased DNA damage levels."
| PMC
SGH affects USP28
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1
4
SGH inhibits USP28.
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1
2
reach
"In terms of mechanism of action, SGH downregulated cell cycle- and nucleotide synthesis related proteins to block cell cycle at G0/G1 phase, reduced the expression levels of glycolytic metabolic enzymes to inhibit glycolysis, and downregulated the important cancer transcription factor c-Myc and the therapeutic target deubiquitinase USP28."
SGH decreases the amount of USP28.
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2
Vismodegib affects USP28
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4
Vismodegib binds USP28.
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3
Vismodegib inhibits USP28.
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1
Vismodegib inhibits USP28. 1 / 1
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1
USP28 affects glycolytic process
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4
USP28 affects Wnt signaling pathway
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3
1
USP28 activates Wnt signaling pathway. 4 / 4
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3
1
eidos
"Our results show that USP28 contributes to the activity of the Wnt signaling pathway through stabilizing TCF7L2 ( Figure 7 ) , at least partially , as it also regulates other members of the TCF / LEF family transcription factors ( Figure 2A ) as well as Forkhead box protein M1 ( FOXM1 ) , another transcription factor involved in Wnt signaling ."
USP28 binds FOXC1.
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1
USP28 affects E3_Ub_ligase
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2
2
USP28 inhibits E3_Ub_ligase.
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2
USP28 binds E3_Ub_ligase.
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2
Trichostatin A affects USP28
3
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3
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Lipopolysaccharide, E coli O55-B5 increases the amount of USP28.
2
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Lipopolysaccharide, E coli O55-B5 decreases the amount of USP28.
1
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USP28 affects vismodegib
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3
USP28 affects cell differentiation
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3
USP28 affects Neoplastic Stem Cells
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3
USP28 activates Neoplastic Stem Cells.
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2
USP28 inhibits Neoplastic Stem Cells.
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1
USP28 inhibits Neoplastic Stem Cells. 1 / 1
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1
eidos
"APC , adenomatous polyposis coli ; DVL , Disheveled ; Fz , frizzled ; GSK3 , glycogen synthase kinase-3 ; LRP , lipoprotein receptor-related ; USP28 , ubiquitin-specific protease 28 As Usp28-deficient mice develop normally , the role of Usp28 in the normal Wnt signaling during embryonic development must be minimal or its absence could be mitigated by unspecified redundant mechanisms , for example , suppressing GSK3beta activity so that TCF7L2 is not ubiquitinated in the first place ."
reach
"A study has proposed a novel mechanism by which USP28 upregulates angiogenesis by antagonizing GSK-3beta (glycogen synthase kinase-3beta) and FBW7 dependent degradation of HIF-1alpha (hypoxia inducible factor-1alpha), a major regulator of angiogenesis, carcinogenesis, and various processes by which cells adapt to hypoxic conditions."
USP28 affects FBXW7-185aa
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3
sparser
"The findings that support this conclusion are the following: (i) the binding of UCK1 to the E3 ligase KLHL2 causes its polyubiquitination at K81 and degradation; (ii) the DUB USP28 binds to UCK1 through interaction with KLHL2 and antagonizes KLHL2-mediated effect on UCK1; (iii) UCK1 deubiquitination by USP28 is dependent on the phosphorylation status of USP28; (iv) USP28 is phosphorylated by 5'-AZA-activated ATM, resulting in disassociation of KLHL2 from USP28 and UCK1 destabilization; (v) ATM also phosphorylates UCK1 at S145, significantly enhancing the KLHL2-UCK1 complex formation; (vi) the knockdown of KLHL2 not only significantly inhibits AML cell proliferation, but also sensitizes AML cells to 5'-AZA-induced apoptosis; and (vii) combinational therapies with 5'-AZA and ectopic USP28 expression enhances the effects of 5'-AZA and induces synergistic lethality at cellular level and in the AML mouse model, which is, however, observed in cells deficient in USP28."
sparser
"The findings that support this conclusion are the following: (i) the binding of UCK1 to the E3 ligase KLHL2 causes its polyubiquitination at K81 and degradation; (ii) the DUB USP28 binds to UCK1 through interaction with KLHL2 and antagonizes KLHL2-mediated effect on UCK1; (iii) UCK1 deubiquitination by USP28 is dependent on the phosphorylation status of USP28; (iv) USP28 is phosphorylated by 5'-AZA-activated ATM, resulting in disassociation of KLHL2 from USP28 and UCK1 destabilization; (v) ATM also phosphorylates UCK1 at S145, significantly enhancing the KLHL2-UCK1 complex formation; (vi) the knockdown of KLHL2 not only significantly inhibits AML cell proliferation, but also sensitizes AML cells to 5'-AZA-induced apoptosis; and (vii) combinational therapies with 5'-AZA and ectopic USP28 expression enhances the effects of 5'-AZA and induces synergistic lethality at cellular level and in the AML mouse model, which is, however, observed in cells deficient in USP28."
FBXW7-185aa affects USP28
|
3
Vemurafenib affects USP28
|
2
Phenylmercury acetate affects USP28
2
|
Panobinostat affects USP28
2
|
P-chloromercuribenzoic acid affects USP28
2
|
MiR-500a-5p affects USP28
|
1
1
MiR-216b affects USP28
|
2
Mercury dibromide affects USP28
2
|
Hsa-miR-363-3p affects USP28
2
|
Entinostat affects USP28
2
|
Bisphenol A affects USP28
2
|
Belinostat affects USP28
2
|
USP28 affects vemurafenib
|
2
USP28 activates vemurafenib. 2 / 2
|
2
USP28 affects ubiquitination
|
2
USP28 affects tumor growth
|
2
USP28 affects signaling
|
2
USP28 affects miR-500a-5p
|
2
USP28 affects cell migration
|
2
USP28 affects cell death
|
1
1
USP28 affects cell adhesion
|
2
USP28 inhibits cell adhesion. 2 / 2
|
2
reach
"In contrast, in a detailed study on the function of USP28 in breast cancer XREF_BIBR, Richter et al. found that USP28 deficiency in breast cancer cells enhances conversion toward a more aggressive phenotype by promoting EMT, proliferation, migration, angiogenesis, and decreased adhesion."
USP28 affects Wnt signaling
|
2
eidos
"To explore how USP28 might be involved in HCC development , we undertook a Gene Set Enrichment Analysis and found a significant positive correlation between USP28 expression and the expression of Wnt signaling pathway genes ( Figure 1D ) , suggesting that USP28 might contribute to Wnt signaling ."
USP28 affects Pancreatic Neoplasms
|
2
USP28 activates Pancreatic Neoplasms. 2 / 2
|
2
USP28 affects Neoplasm Metastasis
|
2
USP28 activates Neoplasm Metastasis. 2 / 2
|
2
USP28 affects JUN_family
|
2
USP28 affects Hemagglutinins
|
2
USP28 affects Fbw7α
|
2
USP28 affects Fbw7alpha
|
2
USP28 affects Cell Survival
|
2
USP28 affects Carcinogenesis
|
1
1
USP28 affects CD44s
|
2
USP28 affects CD44s protein
|
2
USP28 affects CD44 protein stability
|
2
eidos
"ISO attenuated CD44 protein stability by down-regulating USP28 in human BC cells Because ISO treatment not only inhibited endogenous CD44 expression but also reduced ectopic CD44 protein expression in T24T cell , the study next examined if down-regulation of CD44 expression due to ISO was a result of changes in degradation of CD44 protein ."
USP28 affects C-Cdh1
|
2
USP28 affects C-Cdh1 targets
|
2
reach
"This early disassembly of the MRN complex could be prevented by altering the ubiquitination site of Nbs1 or by expressing a deubiquitinase, Usp28, which sufficiently restored homologous recombination repair and ATM, a major checkpoint kinase against DNA DSBs, activation abilities in RTS and RecQL4-depleted cells."
MYC affects Fbw7α
|
2
Hydrogen-Ion Concentration affects USP28
|
2
Hemagglutinins affects USP28
|
2
Fbw7α affects USP28
|
2
E3_Ub_ligase affects USP28
|
2
CD44s affects USP28
|
2
Vorinostat affects USP28
1
|
Unspecified redundant mechanisms affects USP28
|
1
eidos
"APC , adenomatous polyposis coli ; DVL , Disheveled ; Fz , frizzled ; GSK3 , glycogen synthase kinase-3 ; LRP , lipoprotein receptor-related ; USP28 , ubiquitin-specific protease 28 As Usp28-deficient mice develop normally , the role of Usp28 in the normal Wnt signaling during embryonic development must be minimal or its absence could be mitigated by unspecified redundant mechanisms , for example , suppressing GSK3beta activity so that TCF7L2 is not ubiquitinated in the first place ."
Tributylstannane affects USP28
1
|
Sodium arsenite affects USP28
1
|
ShRNA-mediated affects USP28
|
1
Set benzylaminoethanol affects USP28
|
1
Rigosertib sodium affects USP28
|
1
Rigosertib sodium activates mutated USP28. 1 / 1
|
1
Nickel sulfate affects USP28
1
|
Nickel atom affects USP28
1
|
New affects USP28
|
1
Mono(2-ethylhexyl) phthalate affects USP28
1
|
MiR-92b-3p affects USP28
|
1
MiR-4295 maturation affects USP28
|
1
eidos
"The present study found that ISO treatment led to time-dependent increases in Dicer protein abundance , which , in turn , subsequently promoted miR-4295 maturation that resulted in down-regulation of USP28 , acceleration of CD44 protein degradation , and ultimately brought about a significant reduction in stem-like properties of the human BC cells ."
MiR-363-3p affects USP28
|
1
MiR-143-3p affects USP28
|
1
Methylmercury chloride affects USP28
1
|
Leflunomide affects USP28
1
|
Hsa-miR-93-5p affects USP28
1
|
Hsa-miR-92a-3p affects USP28
1
|
Hsa-miR-615-3p affects USP28
1
|
Hsa-miR-5589-3p affects USP28
1
|
Hsa-miR-519d-3p affects USP28
1
|
Hsa-miR-493-5p affects USP28
1
|
Hsa-miR-4729 affects USP28
1
|
Hsa-miR-4668-3p affects USP28
1
|
Hsa-miR-3940-5p affects USP28
1
|
Hsa-miR-367-3p affects USP28
1
|
Hsa-miR-340-5p affects USP28
1
|
Hsa-miR-32-5p affects USP28
1
|
Hsa-miR-25-3p affects USP28
1
|
Hsa-miR-221-3p affects USP28
1
|
Hsa-miR-20b-5p affects USP28
1
|
Hsa-miR-20a-5p affects USP28
1
|
Hsa-miR-20a-3p affects USP28
1
|
Hsa-miR-181a-5p affects USP28
1
|
Hsa-miR-17-5p affects USP28
1
|
Hsa-miR-153-3p affects USP28
1
|
Hsa-miR-1301-3p affects USP28
1
|
Hsa-miR-129-5p affects USP28
1
|
Hsa-miR-122-5p affects USP28
1
|
Hsa-miR-106b-5p affects USP28
1
|
Hsa-let-7g-3p affects USP28
1
|
Hsa-let-7c-3p affects USP28
1
|
Hsa-let-7a-2-3p affects USP28
1
|
H treatment SGH muM PC9 cells muM H157 cells affects USP28
|
1
Formaldehyde affects USP28
1
|
Dorsomorphin affects USP28
1
|
Diclofenac affects USP28
1
|
Decabromodiphenyl ether affects USP28
1
|
D pyrimidine derivative affects USP28
|
1
CircRNA FBXW7 affects USP28
|
1
CircMED27 affects USP28
|
1
Chloroquine affects USP28
1
|
Cadmium dichloride affects USP28
1
|
Brought stem-like properties human BC cells affects USP28
|
1
eidos
"The present study found that ISO treatment led to time-dependent increases in Dicer protein abundance , which , in turn , subsequently promoted miR-4295 maturation that resulted in down-regulation of USP28 , acceleration of CD44 protein degradation , and ultimately brought about a significant reduction in stem-like properties of the human BC cells ."
1
|
Benzo[a]pyrene affects USP28
1
|
Aluminium atom affects USP28
1
|
UbV.USP28 affects USP28
|
1
UbV.28 affects USP28
|
1
USP28Delta 53BP1Delta affects USP28
|
1
1
|
USP28 affects vincristine
|
1
USP28 activates vincristine. 1 / 1
|
1
USP28 affects viability gastric cancer cells
|
1
USP28 affects ubiquitination transcription 7-like TCF7L2
|
1
USP28 affects ubiquitination modification c-Myc
|
1
USP28 affects ubiquitination LEF1
|
1
USP28 affects turnover
|
1
USP28 affects tumor-suppressor genes
|
1
USP28 affects treatment tumors
|
1
USP28 affects translation
|
1
USP28 inhibits translation. 1 / 1
|
1
USP28 affects target c-MYC
|
1
USP28 affects stability PIM1 hypoxia
|
1
USP28 affects stability FBW7-substrates cancer cells
|
1
USP28 affects stability CHK2
|
1
USP28 affects radiosensitivity esophageal cancer cells
|
1
USP28 affects protein stability c-Myc
|
1
USP28 affects protein deubiquitination
|
1
USP28 activates protein deubiquitination. 1 / 1
|
1
USP28 affects p53 protein stability
|
1
USP28 affects p21-dependent cell cycle
|
1
USP28 affects p-Chk1 protein
|
1
USP28 affects oncogenic transformation respiratory cells
|
1
USP28 affects oncogenic reprogramming
|
1
USP28 affects miR-500a-5p breast cancer cell metastasis
|
1
USP28 affects melanoma cell resistance
|
1
USP28 affects localization
|
1
USP28 activates localization. 1 / 1
|
1
USP28 affects lifespans
|
1
USP28 affects inhibition potentiates molecular therapy targeting mutant BRAF PI3K
|
1
USP28 affects homologous recombination
|
1
USP28 activates homologous recombination. 1 / 1
|
1
reach
"This early disassembly of the MRN complex could be prevented by altering the ubiquitination site of Nbs1 or by expressing a deubiquitinase, Usp28, which sufficiently restored homologous recombination repair and ATM, a major checkpoint kinase against DNA DSBs, activation abilities in RTS and RecQL4-depleted cells."
USP28 affects growth lung cancer cells
|
1
USP28 affects growth HepG2 Figures 1F S2A B HuH6 Figures 1G
|
1
USP28 affects different isoforms
|
1
USP28 affects cellular MYC
|
1
USP28 affects cell viability HGC-27 cells
|
1
USP28 affects c-MYC ubiquitylation
|
1
USP28 affects breast cancer cell
|
1
USP28 affects aerobic glycolysis
|
1
USP28 affects aerobic glycolysis colorectal cancer
|
1
USP28 affects accumulate HIF-1alpha protein cells
|
1
USP28 affects Wnt/β-catenin
|
1
USP28 affects Ubiquitination
|
1
USP28 inhibits Ubiquitination. 1 / 1
|
1
USP28 affects UbV.28
|
1
USP28 affects USP28Delta cells
|
1
USP28 affects USP
|
1
USP28 affects TRUSS
|
1
reach
"Other proteins regulating C-MYC stability include : CIP2A, a C-MYC-interacting protein that specifically inhibits PP2A activity against C-MYC; USP28, a de-ubiquitinating enzymes that antagonizes FBW7 and promotes C-MYC stability and TRUSS, a receptor for DDB1 (damage specific DNA binding protein 1)-CUL4 (Cullin 4) E3 ligase complex."
USP28 affects Snail1
|
1
USP28 affects RP23-446O17.1
1
|
USP28 affects RP23-437L13.2
1
|
USP28 affects Proto-Oncogenes
|
1
USP28 activates Proto-Oncogenes. 1 / 1
|
1
USP28 affects Proteasome
|
1
USP28 activates Proteasome. 1 / 1
|
1
|
1
USP28 activates Polycystic Kidney, Autosomal Dominant. 1 / 1
|
1
USP28 affects PIM1/2
|
1
USP28 affects Neoplasm Invasiveness
|
1
USP28 inhibits Neoplasm Invasiveness. 1 / 1
|
1
USP28 affects NSCLC
|
1
reach
"However, in contrast to the results in KRAS positive CRC cell lines, in WI-38 cells KRAS failed to increase ZNF304 protein levels (XREF_FIG) or significantly stimulate USP28 and PRKD1 transcription (XREF_FIG), explaining at least in part why KRAS expression does not result in INK4-ARF silencing."
USP28 affects ISO-induced BC cell sphere
|
1
reach
"A study has proposed a novel mechanism by which USP28 upregulates angiogenesis by antagonizing GSK-3beta (glycogen synthase kinase-3beta) and FBW7 dependent degradation of HIF-1alpha (hypoxia inducible factor-1alpha), a major regulator of angiogenesis, carcinogenesis, and various processes by which cells adapt to hypoxic conditions."
USP28 affects G1
|
1
USP28 affects FBW7alpha
|
1
USP28 affects E3-ligases
|
1
USP28 affects Deubiquitinase
|
1
USP28 inhibits Deubiquitinase. 1 / 1
|
1
USP28 affects Carcinoma, Hepatocellular
|
1
USP28 inhibits Carcinoma, Hepatocellular. 1 / 1
|
1
eidos
"While reports have indicated that a lack of USP28 could reduce colon cancer in mice [ 114 ] and that USP28 could also be a prognostic marker in bladder [ 115 ] and gastric cancers [ 116 ] , a lack of USP28 promoted liver cancer and correlated with a worse survival of patients with invasive ductal breast carcinoma : Mouse xenograft experiments with USP28-lacking breast cancer cells supported these findings [ 117 ] ."
reach
"This early disassembly of the MRN complex could be prevented by altering the ubiquitination site of Nbs1 or by expressing a deubiquitinase, Usp28, which sufficiently restored homologous recombination repair and ATM, a major checkpoint kinase against DNA DSBs, activation abilities in RTS and RecQL4-depleted cells."
USP28 affects C171
|
1
USP28 affects Breast Neoplasms
|
1
USP28 inhibits Breast Neoplasms. 1 / 1
|
1
USP28 affects BRAF protein
|
1
USP28 affects BRAF inhibitor
|
1
USP affects USP28
|
1
UCK1 affects Hemagglutinins
|
1
Streptoglutarimide H affects USP28
|
1
RP23-446O17.1 affects USP28
1
|
RP23-437L13.2 affects USP28
1
|
RNAi affects USP28
|
1
PR-619 affects USP28
|
1
PIM1/2 affects USP28
|
1
MYC affects C171
|
1
reach
"However, in contrast to the results in KRAS positive CRC cell lines, in WI-38 cells KRAS failed to increase ZNF304 protein levels (XREF_FIG) or significantly stimulate USP28 and PRKD1 transcription (XREF_FIG), explaining at least in part why KRAS expression does not result in INK4-ARF silencing."
ISO affects USP28
|
1
Hemagglutinins affects UCK1, and USP28
|
1
Graphical abstract new affects USP28
|
1
Fbw7alpha affects USP28
|
1
FOXC1 affects USP28
|
1
FBW7alpha affects USP28
|
1
E3_Ub_ligase affects TP53
|
1
E3-ligases affects USP28
|
1
|
1
DNA damage response, detection of DNA damage phosphorylates USP28. 1 / 1
|
1
C171 affects USP28
|
1
Air Pollutants, Occupational affects USP28
1
|
ATM/IR affects USP28
|
1
6-propyl-2-thiouracil affects USP28
1
|
3-hydroxyisovaleric acid affects USP28
1
|
1
|
1,3-dinitrobenzene affects USP28
1
|
(R)-adrenaline affects USP28
|
1
(R)-adrenaline increases the amount of USP28. 1 / 1
|
1
2,3',4,4',5-pentachlorobiphenyl affects USP28
1
|
1
|