IndraLab

Statements

USP50 affects STS
| 15
USP50 deubiquitinates STS.
| 11
USP50 deubiquitinates STS. 9 / 9
| 9
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"In conclusion, we here demonstrate a novel regulatory mechanism regarding the ASC protein which is deubiquitinated by USP50 and provide experimental evidence emphasizing the importance of a regulatory mechanism mediated by ubiquitination and deubiquitination in inflammasome activation."
28094437
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"Wild-type USP50 and the Flag-USP50 (H322A) mutant significantly deubiquitinated the ASC protein."
28094437
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"Mechanistically, USP50 accelerates bile acid-induced NLRP3 inflammasome activation and pyroptosis via interacting with and deubiquitinating ASC in macrophages."
38469295
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"Expression of exogenous USP50 greatly decreased ASC ubiquitylation ( Figure 4E )."
38469295
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"However, the Flag-USP50 (C53S) mutant, did not affect polyubiquitination of the ASC protein, indicating that the Cys residue at position 53 is critical for the catalytic activity of USP50 deubiquitination of the ASC protein."
28094437
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"Taken together, these data suggested that USP50 physically interacted with and deubiquitinated ASC to induce ASC speck formation and oligomerization.3.5 USP50 stimulates HMGB1 release in DGR-induced gastric inflammation."
38469295
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"USP50 deubiquitinates the ASC protein."
28094437
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"To further confirm our finding that USP50 deubiquitinates the ASC protein, we performed in vitro deubiquitination assays."
28094437
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"Ubiquitination of Flag-ASC proteins was significantly decreased in the presence of Flag-USP50 protein, indicating that USP50 directly deubiquitinates the polyubiquitination of the ASC protein."
28094437
USP50-H322A deubiquitinates STS. 1 / 1
| 1
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"Wild-type USP50 and the Flag-USP50 (H322A) mutant significantly deubiquitinated the ASC protein."
28094437
Ubiquitinated USP50 leads to the deubiquitination of STS. 1 / 1
| 1
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"The NLRP3 inflammasome is also activated by TRAF3-dependent ubiquitination of ASC and USP50-mediated deubiquitination of ASC (91)."
36875130
USP50 inhibits STS.
| 2
USP50 inhibits STS. 2 / 2
| 2
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"USP50 depletion markedly impedes the formation of ASC oligomer and IL-1beta secretion in both human THP-1 macrophages and mouse BMDMs."
33627128
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"Taken together with our results that USP50 depletion decreases the formation of ASC specks as well as the secretion of IL-lbeta, our findings strongly suggest the possibility that removal of these polyubiquitin chains from ASC protein by USP50 is a crucial step for inflammasome activation."
28094437
USP50 binds STS.
| 2
USP50 binds STS. 2 / 2
| 2
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"Taken together, these data suggested that USP50 physically interacted with and deubiquitinated ASC to induce ASC speck formation and oligomerization.3.5 USP50 stimulates HMGB1 release in DGR-induced gastric inflammation."
38469295
reach
"Therefore, these results show that the binding of USP50 with ASC protein to deubiquitinate K63 linked polyubiquitination is a crucial step for inflammasome activation."
28094437
USP50 affects FlaG
| 15
USP50 binds FlaG. 10 / 15
| 15
sparser
"We used the SMART assay xref to measure the degree of exposed ssDNA directly, growing cells in the presence of the nucleotide analogue BrdU before expression, or not of the shUSP50, and FLAG-USP50 variants."
39284827
sparser
"In shUSP50-expressing cells given a short exposure to HU, we observed increased lengths of exposed BrdU, which could be suppressed by FLAG-USP50 expression but only partially suppressed by I141R-FLAG-USP50 mutant expression (Fig.  xref )."
39284827
sparser
"Moreover, 53BP1 foci were suppressed in shUSP50-expressing cells by additional expression of FLAG-USP50 but not by the I141R-FLAG-USP50 mutant (Fig.  xref )."
39284827
sparser
"To address whether USP50 is relevant to the survival of cells experiencing replicative stress, we examined the ability of shUSP50-expressing cells, complemented with FLAG-USP50, to form colonies after exposure to HU."
39284827
sparser
"Restart could be improved by FLAG-USP50 expression but not by I141R-FLAG-USP50 mutant expression (Fig.  xref ), indicating a requirement for USP50, and the Ile-141 face in the resumption of replication."
39284827
sparser
"To test whether USP50 can bind Ub we expressed FLAG-USP50 and an I141R-FLAG-USP50 mutant along with Myc-tagged Ub (Myc-Ub) and performed FLAG immunoprecipitation."
39284827
sparser
"We next generated a FLAG-tagged USP50 construct resistant to that shRNA, which was integrated into an inducible site, expressed upon doxycycline (Dox) treatment, named FLAG-USP50 hereafter."
39284827
sparser
"Further, FLAG-USP50 expression improved the number of telomeres, whereas complementation with I141R-USP50 did not (Supplementary Fig.  xref )."
39284827
sparser
"In contrast, shUSP50-expressing cells complemented with FLAG-USP50 had replication features comparable to untreated cells, whereas expression of I141R-FLAG-USP50 did not improve replication defects in shUSP50-expressing cells (Fig.  xref ), suggesting a requirement for the Ile-141 face for ongoing replication."
39284827
sparser
"We fractioned cells expressing exogenous FLAG-USP50 and noted a proportion of USP50 co-purified with chromatin, which was increased following HU treatment (Fig.  xref )."
39284827
Ubiquitin affects USP50
| 4 4
Ubiquitin binds USP50.
| 3 4
Ubiquitin binds USP50. 7 / 7
| 3 4
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"To test whether USP50 can bind Ub we expressed FLAG-USP50 and an I141R-FLAG-USP50 mutant along with Myc-tagged Ub (Myc-Ub) and performed FLAG immunoprecipitation."
39284827
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"By comparison, the mutant co-precipitated ~35% of the conjugates precipitated by the WT protein (Fig. 1B), suggesting that USP50 interaction with Ub conjugates is in part through its predicted Ub-binding face."
39284827
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"Using purified Ub, and bacterially expressed USP50, we found USP50 bound Ub chains but not free Ub (Supplementary Fig. 2A, B), suggesting a preference for conjugates.If USP50 has a role in replication, it might be expected to be associated with chromatin."
39284827
sparser
"The Alphafold USP50:Ub structure predicts a complex similar to structures reported for USP domains with Ub (e.g., PDB: 3n3k xref )."
39284827
sparser
"In the predicted USP50:Ub structure, Ub Ile44 is close to USP50 Ile-141 (Fig.  xref ), and leucine or isoleucine in USP50 is at this position in all 24 species (Supplementary Fig.  xref )."
39284827
sparser
"To test whether USP50 can bind Ub we expressed FLAG-USP50 and an I141R-FLAG-USP50 mutant along with Myc-tagged Ub (Myc-Ub) and performed FLAG immunoprecipitation."
39284827
sparser
"By comparison, the mutant co-precipitated ~35% of the conjugates precipitated by the WT protein (Fig.  xref ), suggesting that USP50 interaction with Ub conjugates is in part through its predicted Ub-binding face."
39284827
Ubiquitin activates USP50.
| 1
Ubiquitin activates USP50. 1 / 1
| 1
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"This analysis also revealed high molecular weight bands immunoreactive with anti-FLAG following MG132 treatment, suggesting USP50 is itself Ub-modified and processed through the proteasome.The increased co-purification of USP50 with chromatin observed after HU treatment suggested the potential for association at or near stalled replication forks."
39284827
USP50 affects HMGB1
| 2 6
USP50 binds HMGB1.
| 6
HMGB1 binds USP50. 6 / 6
| 6
sparser
"In order to investigate the involvement of the USP50-HMGB1 axis in DGR-induced gastric tumorigenesis, gastric cancer cell lines SNU216 and HGC27 were co-cultured with conditioned media (CM) from macrophages exposed to TDCA (TDCA-CM)."
38469295
sparser
"USP50-HMGB1 axis promotes tumor proliferation and invasion through PI3K/AKT and MAPK/ERK pathways."
38469295
sparser
"To confirm that USP50-HMGB1 axis-driven gastric tumorigenesis is mediated by the PI3K/AKT and MAPK/ERK pathways, herein we utilized ERK1/2 inhibitor SCH772984 and AKT inhibitor MK-2206."
38469295
sparser
"In summary, the USP50-HMGB1 axis facilitates gastric tumorigenesis through the PI3K/AKT and MAPK/ERK pathways."
38469295
sparser
"These results suggest that the USP50-HMGB1 axis may contribute to gastric tumorigenesis."
38469295
sparser
"USP50-HMGB1 axis contributes to DGR-induced gastric tumorigenesis."
38469295
USP50 increases the amount of HMGB1.
| 2
USP50 increases the amount of HMGB1. 2 / 2
| 2
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"Enhancing USP50 expression amplified bile acid-induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and subsequent high-mobility group box protein 1 (HMGB1) release, while USP50 deficiency resulted in the reversed alteration."
38469295
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"Our study also found HMGB1 release can be enhanced by overexpression of USP50 in macrophages with bile acids stimulated."
38469295
USP50 affects XRCC6
1 | 6
USP50 inhibits XRCC6.
| 4
USP50 inhibits XRCC6. 4 / 4
| 4
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"These data suggest that USP50 reduces Ku70 protein stability."
29101126
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"USP50 reduces Ku70 protein stability without affecting its mRNA levels."
29101126
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"Thus, we hypothesize that USP50 mediated Ku70 degradation might be through targeting a ubiquitin E3 ligase that ubiquitinates and degrades Ku70."
29101126
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"Interestingly, USP50 associates with the Ku70 protein and reduces the half-life of Ku70 protein."
29101126
USP50 binds XRCC6.
1 | 1
USP50 binds XRCC6. 1 / 2
1 | 1
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"This is also the first study to demonstrate an interaction between USP50 and Ku70."
29101126
USP50 activates XRCC6.
| 1
USP50 activates XRCC6. 1 / 1
| 1
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"Additional studies are necessary to elucidate the molecular mechanisms of USP50 mediated destabilization of Ku70 protein."
29101126
USP50 affects Ubiquitin
| 3 4
Ubiquitin binds USP50. 7 / 7
| 3 4
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"To test whether USP50 can bind Ub we expressed FLAG-USP50 and an I141R-FLAG-USP50 mutant along with Myc-tagged Ub (Myc-Ub) and performed FLAG immunoprecipitation."
39284827
reach
"By comparison, the mutant co-precipitated ~35% of the conjugates precipitated by the WT protein (Fig. 1B), suggesting that USP50 interaction with Ub conjugates is in part through its predicted Ub-binding face."
39284827
reach
"Using purified Ub, and bacterially expressed USP50, we found USP50 bound Ub chains but not free Ub (Supplementary Fig. 2A, B), suggesting a preference for conjugates.If USP50 has a role in replication, it might be expected to be associated with chromatin."
39284827
sparser
"The Alphafold USP50:Ub structure predicts a complex similar to structures reported for USP domains with Ub (e.g., PDB: 3n3k xref )."
39284827
sparser
"In the predicted USP50:Ub structure, Ub Ile44 is close to USP50 Ile-141 (Fig.  xref ), and leucine or isoleucine in USP50 is at this position in all 24 species (Supplementary Fig.  xref )."
39284827
sparser
"To test whether USP50 can bind Ub we expressed FLAG-USP50 and an I141R-FLAG-USP50 mutant along with Myc-tagged Ub (Myc-Ub) and performed FLAG immunoprecipitation."
39284827
sparser
"By comparison, the mutant co-precipitated ~35% of the conjugates precipitated by the WT protein (Fig.  xref ), suggesting that USP50 interaction with Ub conjugates is in part through its predicted Ub-binding face."
39284827
USP50 affects PYCARD
3 | 1
USP50 binds PYCARD. 1 / 7
3 | 1
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"We further identify that PM binds the Cys53 site of deubiquitinase USP50 through the Michael-acceptor and blocks the binding of USP50 to PYCARD/ASC, thereby reducing USP50-mediated cleavage of K63-linked ubiquitin chains of PYCARD/ASC."
37647255
USP50 affects CPT1A
3 | 1 3
USP50 binds CPT1A.
3 | 3
CPT1A binds USP50. 3 / 6
3 | 3
sparser
"Additionally, CPT1a interacted with USP50 in 293T cells transfected with flag-USP50 (Figure xref B)."
34976224
sparser
"These observations suggest that upon LPS treatment, mitochondrial STAT3 could induce CPT1a-USP50 binding by mediating USP50 expression, leading to CPT1a stabilization, an increase in FAO and higher ATP production."
34976224
sparser
"In comparison, in the LPS-treatedRosa26 LSL-MLS-mSTAT3 macrophage lysates, CPT1a pulled down much less USP50 (Figure xref C, IP Lane 1, xref A), suggesting that mitochondrial STAT3 could contribute to CPT1a stabilization by influencing CPT1a-USP50 binding, at least partially."
34976224
USP50 activates CPT1A.
| 1
USP50 activates CPT1A. 1 / 1
| 1
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"Our study results further suggest that the pharmacological blockade of mitochondrial STAT3 function by curcumin could be a promising treatment strategy for sepsis, metabolic disorders, and other inflammatory diseases.Although our study demonstrates that in the presence of LPS, mitochondrial STAT3 drives FAO by inducing CPT1a stabilization mediated by USP50 in macrophages, several questions emerge from our study."
34976224
USP50 affects AS-C
| 7
USP50 binds AS-C. 7 / 7
| 7
sparser
"Coimmunoprecipitation assays indicated that USP50 strongly binds to the ASC adaptor protein, although it also interacted weakly with NLRP3 (Fig. xref A)."
28094437
sparser
"Therefore, these results show that the binding of USP50 with ASC protein to deubiquitinate K63‐linked polyubiquitination is a crucial step for inflammasome activation."
28094437
sparser
"Mechanically, USP50 physically interacts with ASC, reducing its K63-linked ubiquitination and enhancing ASC oligomerization, subsequently promoting the assembly and activation of the NLRP3 inflammasome."
38469295
sparser
"USP50 binds to the ASC adaptor protein and is required for NLRP3‐induced ASC speck formation and oligomerization."
28094437
sparser
"Further investigations revealed that USP50 interacts with ASC proteins and deubiquitinates K63-linked ASC polyubiquitination ( xref )."
40028334
sparser
"Based on the interaction between USP50 and ASC protein, we next investigated whether USP50 knockdown affects inflammasome activation by analyzing the formation of ASC specks."
28094437
sparser
"A recent report further suggested that USP50 binds ASC and deubiquitinates K63-linked polyubiquitin chains on ASC (citation)."
29031697
USP50 affects ACE2
4 | 2 1
USP50 binds ACE2.
4 | 1
ACE2 binds USP50. 1 / 5
4 | 1
sparser
"VitC blocks the USP50-ACE2 interaction, thus promoting K48-linked polyubiquitination of ACE2 at Lys788 and subsequent degradation of ACE2 without affecting its transcriptional expression."
36876523
USP50 inhibits ACE2.
| 1
USP50 inhibits ACE2. 1 / 1
| 1
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"Overexpression of USP50 reduces ACE2 Lys48-linked ubiquitination and enhances ACE2 protein stability in human HEK293T cells [153]."
37608279
USP50 activates ACE2.
| 1
USP50 activates ACE2. 1 / 1
| 1
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"Overexpression of USP50 reduces ACE2 Lys48-linked ubiquitination and enhances ACE2 protein stability in human HEK293T cells [153]."
37608279
PYCARD affects USP50
3 | 1
USP50 binds PYCARD. 1 / 7
3 | 1
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"We further identify that PM binds the Cys53 site of deubiquitinase USP50 through the Michael-acceptor and blocks the binding of USP50 to PYCARD/ASC, thereby reducing USP50-mediated cleavage of K63-linked ubiquitin chains of PYCARD/ASC."
37647255
AS-C affects USP50
| 7
USP50 binds AS-C. 7 / 7
| 7
sparser
"Coimmunoprecipitation assays indicated that USP50 strongly binds to the ASC adaptor protein, although it also interacted weakly with NLRP3 (Fig. xref A)."
28094437
sparser
"Therefore, these results show that the binding of USP50 with ASC protein to deubiquitinate K63‐linked polyubiquitination is a crucial step for inflammasome activation."
28094437
sparser
"Mechanically, USP50 physically interacts with ASC, reducing its K63-linked ubiquitination and enhancing ASC oligomerization, subsequently promoting the assembly and activation of the NLRP3 inflammasome."
38469295
sparser
"USP50 binds to the ASC adaptor protein and is required for NLRP3‐induced ASC speck formation and oligomerization."
28094437
sparser
"Further investigations revealed that USP50 interacts with ASC proteins and deubiquitinates K63-linked ASC polyubiquitination ( xref )."
40028334
sparser
"Based on the interaction between USP50 and ASC protein, we next investigated whether USP50 knockdown affects inflammasome activation by analyzing the formation of ASC specks."
28094437
sparser
"A recent report further suggested that USP50 binds ASC and deubiquitinates K63-linked polyubiquitin chains on ASC (citation)."
29031697
USP50 affects WEE1
| 6
USP50 activates WEE1.
| 5
USP50 activates WEE1. 5 / 5
| 5
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"USP50 (ubiquitin specific protease 50), a deubiqitinating enzyme (DUB), prevents Wee1 degradation, thereby repressing entry into mitosis following activation of the G2/M DNA damage checkpoint."
26358502
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"In response to DNA damage, USP50 accumulates in the nucleus and may act through an HSP90 dependent mechanism to counteract CDC25B mitotic inducing activity and prevent Wee1 degradation, thereby repressing entry into mitosis following activation of the DNA damage checkpoint [XREF_BIBR]."
28031783
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"HSP90 regulates the DUB activity of USP19 and promotes USP50-mediated Wee1 stability ; however, a DUB for HSP90 has not been reported."
38307937
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"USP50 engages with HSP90 and modulates the protein abundance of Wee1, a pivotal element in G2/M cell cycle arrest (19)."
38469295
reach
"We propose that USP50 may act through a HSP90 dependent mechanism to counteract CDC25B mitotic inducing activity and prevent Wee1 degradation, thereby repressing entry into mitosis following activation of the DNA damage checkpoint."
20930503
USP50 inhibits WEE1.
| 1
USP50 inhibits WEE1. 1 / 1
| 1
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"We also demonstrate USP50 depletion causes a loss in accumulation of the HSP90 client Wee1, which is an essential component of the G2/M cell cycle arrest."
20930503
HMGB1 affects USP50
| 6
HMGB1 binds USP50. 6 / 6
| 6
sparser
"In order to investigate the involvement of the USP50-HMGB1 axis in DGR-induced gastric tumorigenesis, gastric cancer cell lines SNU216 and HGC27 were co-cultured with conditioned media (CM) from macrophages exposed to TDCA (TDCA-CM)."
38469295
sparser
"USP50-HMGB1 axis promotes tumor proliferation and invasion through PI3K/AKT and MAPK/ERK pathways."
38469295
sparser
"To confirm that USP50-HMGB1 axis-driven gastric tumorigenesis is mediated by the PI3K/AKT and MAPK/ERK pathways, herein we utilized ERK1/2 inhibitor SCH772984 and AKT inhibitor MK-2206."
38469295
sparser
"In summary, the USP50-HMGB1 axis facilitates gastric tumorigenesis through the PI3K/AKT and MAPK/ERK pathways."
38469295
sparser
"These results suggest that the USP50-HMGB1 axis may contribute to gastric tumorigenesis."
38469295
sparser
"USP50-HMGB1 axis contributes to DGR-induced gastric tumorigenesis."
38469295
CPT1A affects USP50
3 | 3
CPT1A binds USP50. 3 / 6
3 | 3
sparser
"Additionally, CPT1a interacted with USP50 in 293T cells transfected with flag-USP50 (Figure xref B)."
34976224
sparser
"These observations suggest that upon LPS treatment, mitochondrial STAT3 could induce CPT1a-USP50 binding by mediating USP50 expression, leading to CPT1a stabilization, an increase in FAO and higher ATP production."
34976224
sparser
"In comparison, in the LPS-treatedRosa26 LSL-MLS-mSTAT3 macrophage lysates, CPT1a pulled down much less USP50 (Figure xref C, IP Lane 1, xref A), suggesting that mitochondrial STAT3 could contribute to CPT1a stabilization by influencing CPT1a-USP50 binding, at least partially."
34976224
USP50 affects DNA2
| 5
USP50 activates DNA2.
| 3
USP50 activates DNA2. 3 / 3
| 3
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"USP50 suppresses alternative RecQ helicase use and deleterious DNA2 activity during replication."
39284827
reach
"We found that DNA2 or RECQL4/5 depletion, like USP50 loss, reduced cell survival (Fig. 5J)."
39284827
reach
"USP50 suppresses alternative RecQ helicase use and deleterious DNA2 activity during replication."
38260523
USP50 inhibits DNA2.
| 2
USP50 inhibits DNA2. 2 / 2
| 2
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"Further, since cells lacking FEN1 also show DNA2 and RECQL4/5-dependent suppression of replication restart, we suggest a model where USP50’s support of FEN1 restricts DNA2 and RECQL4/5 usage (Fig. 6A)."
39284827
reach
"In summary, in USP50-depleted cells, RECQL4, RECQL5 and DNA2 show aberrant localisation, suppress ongoing replication and promote spontaneous 53BP1 foci, they also suppress restart and increase ssDNA following exposure to HU."
39284827
ACE2 affects USP50
4 | 1
ACE2 binds USP50. 1 / 5
4 | 1
sparser
"VitC blocks the USP50-ACE2 interaction, thus promoting K48-linked polyubiquitination of ACE2 at Lys788 and subsequent degradation of ACE2 without affecting its transcriptional expression."
36876523
USP50 affects FEN1
| 4
USP50 activates FEN1. 4 / 4
| 4
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"USP50 supports WRN:FEN1 at stalled replication forks, suppresses MUS81-dependent fork collapse and restricts double-strand DNA breaks at GC-rich sequences."
38260523
reach
"USP50 supports FEN1 localisation at stalled forks."
39284827
reach
"Further, since cells lacking FEN1 also show DNA2 and RECQL4/5-dependent suppression of replication restart, we suggest a model where USP50’s support of FEN1 restricts DNA2 and RECQL4/5 usage (Fig. 6A)."
39284827
reach
"Thus, USP50 promotes FEN1 presence at stalled forks."
39284827
USP8 affects USP50
| 3
USP50 binds USP8. 3 / 3
| 3
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"Taken together, these results indicate that USP-50/USP8 recruitment dissociates RABX-5 from endosomes, and subsequently diminish Rab5 signaling."
39576689
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"In conclusion, we propose that the recruitment of USP-50/USP8, dependent on Rabex5, dissociates Rabex5 from EEs."
39576689
reach
"Instead of stabilizing Rabex5, the USP-50/USP8 recruitment dissociates Rabex5 from endosomes and meanwhile enrolls the Rab7 GEF SAND-1/Mon1."
39576689
USP50 affects TP53BP1
| 3
USP50 inhibits TP53BP1. 3 / 3
| 3
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"Moreover, 53BP1 foci were suppressed in shUSP50-expressing cells by additional expression of FLAG-USP50 but not by the I141R-FLAG-USP50 mutant (Fig. 2F)."
39284827
reach
"These data show both human and murine USP50 can act to suppress 53BP1 accumulations, implying a conserved role for USP50 in promoting replication.To address whether USP50 is relevant to the survival of cells experiencing replicative stress, we examined the ability of shUSP50-expressing cells, complemented with FLAG-USP50, to form colonies after exposure to HU."
39284827
reach
"In summary, in USP50-depleted cells, RECQL4, RECQL5 and DNA2 show aberrant localisation, suppress ongoing replication and promote spontaneous 53BP1 foci, they also suppress restart and increase ssDNA following exposure to HU."
39284827
XRCC6 affects USP50
1 | 1
USP50 binds XRCC6. 1 / 2
1 | 1
reach
"This is also the first study to demonstrate an interaction between USP50 and Ku70."
29101126
USP50 affects helicase
| 2
USP50 inhibits helicase. 2 / 2
| 2
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"USP50 suppresses alternative RecQ helicase use and deleterious DNA2 activity during replication."
39284827
reach
"USP50 suppresses alternative RecQ helicase use and deleterious DNA2 activity during replication."
38260523
USP50 affects WRN
| 2
USP50 activates WRN. 2 / 2
| 2
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"USP50 supports WRN:FEN1 at stalled replication forks, suppresses MUS81-dependent fork collapse and restricts double-strand DNA breaks at GC-rich sequences."
38260523
reach
"These data suggest that USP50 promotes the ability of WRN to associate with chromatin and with the 9-1-1.We were curious to test whether USP50 impacts WRN turnover and treated cells with the translation-inhibitor cycloheximide to observe WRN degradation rates."
39284827
USP50 affects RABX-5
| 2
USP50 binds RABX-5. 2 / 2
| 2
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"By searching the putative USP-50-binding partners, we found that USP-50 can bind to RABX-5, the worm homolog of Rabex5 protein (Figure 4A and B)."
39576689
reach
"Further including Vps9 domain enhances the molecular interaction between RABX-5 and USP-50 (Figure 4C and D)."
39576689
USP50 affects RAB5A
| 2
USP50 inhibits RAB5A.
| 1
USP50 inhibits RAB5A. 1 / 1
| 1
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"Overexpression of RAB-7 rescued the enlarged EE phenotype of usp-50 mutants (Figure 6U–X), further supporting the idea that USP-50/USP8 downregulates Rab5 signaling and meanwhile promotes Rab7 activation, thus facilitating the EE-to-LE conversion."
39576689
USP50 increases the amount of RAB5A.
| 1
Mutated USP50 increases the amount of RAB5A. 1 / 1
| 1
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"In addition, the total RAB-5 protein level is increased by usp-50 mutation (Figure 5—figure supplement 2G and H), which implies that RAB-5 activation may stabilize RAB-5 protein."
39576689
USP50 affects NLRP3
| 2
USP50 activates NLRP3. 1 / 1
| 1
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"IL-1β ( Figures 3C-F ) and IL-18 ( Figures 3G-J ) levels measured by ELISA further corroborated the positive regulation of USP50 on bile acid-induced NLRP3 inflammasome activation.The basic levels of the members of NLRP3 inflammasome were not affected by modulating USP50 expression without TDCA treatment."
38469295
Ubiquitinated USP50 activates NLRP3. 1 / 1
| 1
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"The NLRP3 inflammasome is also activated by TRAF3-dependent ubiquitination of ASC and USP50-mediated deubiquitination of ASC (91)."
36875130
USP50 affects NLRP3 inflammasome
| 1
USP50 inhibits NLRP3 inflammasome. 1 / 2
| 1
eidos
"In addition , USP50 can also inhibit NLRP3 inflammasome degradation through the autophagy pathway as mentioned above ( Lee et al ., 2017 ) ."
34966378
USP50 affects IL1B
| 2
USP50 inhibits IL1B. 2 / 2
| 2
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"USP50 depletion markedly impedes the formation of ASC oligomer and IL-1beta secretion in both human THP-1 macrophages and mouse BMDMs."
33627128
reach
"In contrast, USP50 depletion significantly decreased IL-1beta secretion, suggesting the possibility that USP50 is a positive regulator in inflammasome activation."
28094437
USP50 affects IKBKB
| 1 1
USP50 binds IKBKB. 2 / 2
| 1 1
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"As binding of IKBKB to Usp50 can cause I kappa B kinase beta (Ikkβ) ubiquitination, inhibition of IKBKB and Usp50 caused a reduction in Ikkβ ubiquitination, which in turn blocked NF-κB and hedgehog signaling pathway activation, reversing EMT progression."
37810708
sparser
"As binding of IKBKB to Usp50 can cause I kappa B kinase beta (Ikkβ) ubiquitination, inhibition of IKBKB and Usp50 caused a reduction in Ikkβ ubiquitination, which in turn blocked NF-κB and hedgehog signaling pathway activation, reversing EMT progression."
37810708
STS affects USP50
| 2
USP50 binds STS. 2 / 2
| 2
reach
"Taken together, these data suggested that USP50 physically interacted with and deubiquitinated ASC to induce ASC speck formation and oligomerization.3.5 USP50 stimulates HMGB1 release in DGR-induced gastric inflammation."
38469295
reach
"Therefore, these results show that the binding of USP50 with ASC protein to deubiquitinate K63 linked polyubiquitination is a crucial step for inflammasome activation."
28094437
RABX-5 affects USP50
| 2
USP50 binds RABX-5. 2 / 2
| 2
reach
"By searching the putative USP-50-binding partners, we found that USP-50 can bind to RABX-5, the worm homolog of Rabex5 protein (Figure 4A and B)."
39576689
reach
"Further including Vps9 domain enhances the molecular interaction between RABX-5 and USP-50 (Figure 4C and D)."
39576689
IKBKB affects USP50
| 1 1
USP50 binds IKBKB. 2 / 2
| 1 1
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"As binding of IKBKB to Usp50 can cause I kappa B kinase beta (Ikkβ) ubiquitination, inhibition of IKBKB and Usp50 caused a reduction in Ikkβ ubiquitination, which in turn blocked NF-κB and hedgehog signaling pathway activation, reversing EMT progression."
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"As binding of IKBKB to Usp50 can cause I kappa B kinase beta (Ikkβ) ubiquitination, inhibition of IKBKB and Usp50 caused a reduction in Ikkβ ubiquitination, which in turn blocked NF-κB and hedgehog signaling pathway activation, reversing EMT progression."
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Tdc affects USP50
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Tdc increases the amount of USP50. 1 / 1
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"Additionally, in PMA-differentiated U937 and RAW264.7 macrophages, TDCA significantly enhanced the expression of USP50 at both mRNA and protein levels, following a pattern reliant on time or dosage ( Figures 2F-I ; Supplementary Figures 2D, E )."
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Pyridostatin affects USP50
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Pyridostatin inhibits USP50. 1 / 1
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"Suppression of DNA2 improves HU resistance and telomere stability, and RECQL4 and RECQL5 suppression improves pyridostatin resistance of USP50-depleted cells."
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Melatonin affects USP50
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Melatonin increases the amount of USP50. 1 / 1
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"Melatonin upregulates the expression of Bcl-2 interacting mediator of cell death (Bim), a proapoptotic protein [48], as well as DUBs such as OTUD1, USP2, and USP50."
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VCP affects USP50
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VCP inhibits USP50. 1 / 1
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"MG132 treatment, but not VCP suppression, also increased the chromatin association of USP50 (Fig. 1D)."
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USP50 affects oligomer IL-1beta secretion human THP-1 macrophages mouse BMDMs
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USP50 activates oligomer IL-1beta secretion human THP-1 macrophages mouse BMDMs. 1 / 1
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"USP50 depletion markedly impedes the formation of ASC oligomer and IL-1beta secretion in both human THP-1 macrophages and mouse BMDMs ."
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USP50 affects group box protein 1
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USP50 increases the amount of group box protein 1. 1 / 1
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"Enhancing USP50 expression amplified bile acid-induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and subsequent high-mobility group box protein 1 (HMGB1) release, while USP50 deficiency resulted in the reversed alteration."
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USP50 affects apoptotic process
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USP50 inhibits apoptotic process. 1 / 1
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"Taken together, these findings suggest a model where USP50 and Ku70 may stabilize Mcl-1 and prevent apoptosis in the late stages of erythropoiesis."
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USP50 affects WRN-FEN1
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USP50 activates WRN-FEN1. 1 / 1
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"We find that USP50 supports proper WRN-FEN1 localisation at or near stalled replication forks."
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USP50 affects USP50
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USP50 inhibits USP50. 1 / 1
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"Intriguingly, the slowing/stalling of forks in RECQL5-depleted cells was restored by loss of USP50, suggesting USP50 presence is harmful to ongoing replication when RECQL5 is reduced."
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USP50 affects RECQL5
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USP50 inhibits RECQL5. 1 / 1
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"In summary, in USP50-depleted cells, RECQL4, RECQL5 and DNA2 show aberrant localisation, suppress ongoing replication and promote spontaneous 53BP1 foci, they also suppress restart and increase ssDNA following exposure to HU."
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USP50 affects RECQL4/5
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USP50 activates RECQL4/5. 1 / 1
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"We found that DNA2 or RECQL4/5 depletion, like USP50 loss, reduced cell survival (Fig. 5J)."
39284827
USP50 affects RECQL4/5 usage
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USP50 inhibits RECQL4/5 usage. 1 / 1
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"Further, since cells lacking FEN1 also show DNA2 and RECQL4/5-dependent suppression of replication restart, we suggest a model where USP50’s support of FEN1 restricts DNA2 and RECQL4/5 usage (Fig. 6A)."
39284827
USP50 affects RECQL4
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USP50 inhibits RECQL4. 1 / 1
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"In summary, in USP50-depleted cells, RECQL4, RECQL5 and DNA2 show aberrant localisation, suppress ongoing replication and promote spontaneous 53BP1 foci, they also suppress restart and increase ssDNA following exposure to HU."
39284827
USP50 affects Pristimerin
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Pristimerin binds USP50 and Cys53. 1 / 1
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"We further identify that PM binds the Cys53 site of deubiquitinase USP50 through the Michael-acceptor and blocks the binding of USP50 to PYCARD/ASC, thereby reducing USP50-mediated cleavage of K63-linked ubiquitin chains of PYCARD/ASC."
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"Furthermore, silencing USP50 suppressed the OCR (Figure 7F)."
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USP50 affects NFkappaB
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NFkappaB binds USP50. 1 / 1
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"The ChIP assays revealed that NF-κB bound the USP50 promoter."
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USP50 affects MYC
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USP50 binds MYC. 1 / 1
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"However, the levels of polyubiquitinated CPT1a protein were decreased in the 293T cells transfected with flag-CPT1a, myc-USP50 and HA-ubiquitin (Figure xref E)."
34976224
USP50 affects MCOLN1
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USP50 inhibits mutated MCOLN1. 1 / 1
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"It was recently reported that, in C. elegans, depletion of the ESCRT associated de-ubiquitination factors did2, usp50 (UBPY in humans) and ego-2 (HD-PTP in humans) rescues the embryonic lethality of T[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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USP50 affects INDUCE-seq
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USP50 inhibits INDUCE-seq. 1 / 1
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"To understand whether specific regions of DNA are sensitive to USP50 loss, we identified the sequences adjacent to DNA DSB sites in control and USP50-depleted cells by employing INDUCE-seq."
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USP50 affects IL1
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USP50 activates IL1. 1 / 1
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"Consistently, USP50 depletion impeded the induction of caspase-1 cleavage and IL-1β/IL-18 maturation ( Figure 3B ; Supplementary Figures 3E, F )."
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USP50 affects IL-lbeta
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USP50 inhibits IL-lbeta. 1 / 1
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"Taken together with our results that USP50 depletion decreases the formation of ASC specks as well as the secretion of IL-lbeta, our findings strongly suggest the possibility that removal of these polyubiquitin chains from ASC protein by USP50 is a crucial step for inflammasome activation."
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USP50 affects IKK_complex
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USP50 leads to the ubiquitination of IKK_complex. 1 / 1
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"As binding of IKBKB to Usp50 can cause I kappa B kinase beta (Ikkβ) ubiquitination, inhibition of IKBKB and Usp50 caused a reduction in Ikkβ ubiquitination, which in turn blocked NF-κB and hedgehog signaling pathway activation, reversing EMT progression."
37810708
USP50 affects Flag
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USP50 binds Flag. 1 / 1
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"Flag-USP50 was stable expressed in U937 cells via lentiviral transfection and then co-IP was conducted with anti-Flag antibody."
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USP50 affects ERK
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USP50 activates phosphorylated ERK. 1 / 1
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"Depletion of USP50 in macrophages impaired the elevation of p-AKT (S473) and p-ERK1/2 (T202/Y204) induced by the co-culture exposed to TDCA-CM ( Figure 7B ; Supplementary Figures 5C, D )."
38469295
USP50 affects Cys53
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Pristimerin binds USP50 and Cys53. 1 / 1
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"We further identify that PM binds the Cys53 site of deubiquitinase USP50 through the Michael-acceptor and blocks the binding of USP50 to PYCARD/ASC, thereby reducing USP50-mediated cleavage of K63-linked ubiquitin chains of PYCARD/ASC."
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USP50 affects Carcinogenesis
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USP50 activates Carcinogenesis. 1 / 1
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"USP50 regulates NLRP3 inflammasome activation in duodenogastric reflux-induced gastric tumorigenesis."
38469295
USP50 affects CPT1a-USP50 binding
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USP50 activates CPT1a-USP50 binding. 1 / 1
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eidos
"These observations suggest that upon LPS treatment , mitochondrial STAT3 could induce CPT1a-USP50 binding by mediating USP50 expression , leading to CPT1a stabilization , an increase in FAO and higher ATP production ."
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USP50 affects CPT1a stabilization
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USP50 activates CPT1a stabilization. 1 / 1
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"Upon the LPS stimulation , mitochondrial STAT3 could induce CPT1a stabilization by promoting USP50 expression and facilitating CPT1a-USP50 binding , leading to a switch from glucose to an increased reliance on FAO for ATP production , which , in turn , further enhanced NF-kappaB nuclear localization , leading to a great amount of cytokine production ."
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USP50 affects CASP1
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USP50 inhibits CASP1. 1 / 1
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"Consistently, USP50 depletion impeded the induction of caspase-1 cleavage and IL-1β/IL-18 maturation ( Figure 3B ; Supplementary Figures 3E, F )."
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USP50 affects AKT
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USP50 activates phosphorylated AKT. 1 / 1
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"Depletion of USP50 in macrophages impaired the elevation of p-AKT (S473) and p-ERK1/2 (T202/Y204) induced by the co-culture exposed to TDCA-CM ( Figure 7B ; Supplementary Figures 5C, D )."
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USP50 inhibits 5-bromo-2'-deoxyuridine. 1 / 1
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"In shUSP50-expressing cells given a short exposure to HU, we observed increased lengths of exposed BrdU, which could be suppressed by FLAG-USP50 expression but only partially suppressed by I141R-FLAG-USP50 mutant expression (Fig. 2E)."
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STAT3 affects USP50
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STAT3 increases the amount of USP50. 1 / 1
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"Upon the LPS stimulation, mitochondrial STAT3 could induce CPT1a stabilization by promoting USP50 expression and facilitating CPT1a-USP50 binding, leading to a switch from glucose to an increased reliance on FAO for ATP production, which, in turn, further enhanced NF-κB nuclear localization, leading to a great amount of cytokine production."
34976224
Pristimerin affects USP50
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Pristimerin binds USP50 and Cys53. 1 / 1
| 1
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"We further identify that PM binds the Cys53 site of deubiquitinase USP50 through the Michael-acceptor and blocks the binding of USP50 to PYCARD/ASC, thereby reducing USP50-mediated cleavage of K63-linked ubiquitin chains of PYCARD/ASC."
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NFkappaB affects USP50
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NFkappaB binds USP50. 1 / 1
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"The ChIP assays revealed that NF-κB bound the USP50 promoter."
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MYC affects USP50
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USP50 binds MYC. 1 / 1
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"However, the levels of polyubiquitinated CPT1a protein were decreased in the 293T cells transfected with flag-CPT1a, myc-USP50 and HA-ubiquitin (Figure xref E)."
34976224
Flag affects USP50
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USP50 binds Flag. 1 / 1
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"Flag-USP50 was stable expressed in U937 cells via lentiviral transfection and then co-IP was conducted with anti-Flag antibody."
38469295
Cys53 affects USP50
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Pristimerin binds USP50 and Cys53. 1 / 1
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"We further identify that PM binds the Cys53 site of deubiquitinase USP50 through the Michael-acceptor and blocks the binding of USP50 to PYCARD/ASC, thereby reducing USP50-mediated cleavage of K63-linked ubiquitin chains of PYCARD/ASC."
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