IndraLab

Statements

Delta-actitoxin-Avd1a binds OTUD6B. 10 / 609
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"To the best of our knowledge, the present study was the first to investigate the role of OTUD6B-AS1 in CRC, and to examine whether OTUD6B-AS1 could affect the proliferation, invasion and migration of CRC cells by regulating miR-3171."
33574932
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"As shown in Figures xref and xref , compared with untreated xenograft tumors, more obvious apoptosis was detected in xenograft tumors in which lncRNA OTUD6B-AS1 was overexpressed or those treated with As 2 O 3 ( P < 0.01)."
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"In conclusion, OTUD6B-AS1 which acts as a tumor suppressor inhibits the viability, migration, and invasion of thyroid carcinomas by targeting miR-183-5p and miR-21."
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"The lncRNA ovarian tumor domain containing 6B antisense RNA1 (OTUD6B-AS1) can promote GPX4-mediated ferroptosis and increase the radiosensitivity of colorectal cancer cells ( xref )."
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"A previous study revealed that lncRNA OTUD6B-AS1 promoted autophagy in triple-negative breast cancer cells by regulation of the miR-26a/MTDH pathway [ xref ]."
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"OTUD6B-AS1 is expressed at lower levels in CRC tissues and cells."
39026978
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"Recent accumulating evidence has indicated that lncRNAs, such as OTUD6B-AS1, URRCC, HOTAIRM1 and MRCCAT1, play important regulatory roles in diverse biological processes in ccRCC [ xref – xref ]."
| PMC
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"Mechanistic studies have shown that OTUD6B-AS1 inhibits CRC proliferation by sponging miR-21-5p and upregulating PNRC2 ( xref )."
39026978
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"Cai et al. suggest that the overexpression of OTUD6B-AS1 promotes apoptosis through the OTUD6B-AS1/miR-21-5p/PNRC2 axis ( xref )."
39026978
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"Additionally, the downregulation of lncRNA OTUD6B-AS1, functioning as a competing ceRNA, modulates the expression of miR-26a-5p, inhibits autophagy, and improves paclitaxel-induced cytotoxicity ( xref )."
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Delta-actitoxin-Avd1a binds OTUD6B and mtf1. 1 / 1
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"As shown in xref , the luciferase activity driven by the WT promoter sequence was markedly reduced by MTF1 knockdown, indicating that the WT sites are required for binding of MTF1 to the lncRNA OTUD6B-AS1 promoter."
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OTUD6B affects LIN28B
7 | 13 14
OTUD6B binds LIN28B.
7 | 5 14
OTUD6B binds LIN28B. 10 / 26
7 | 5 14
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"Thus, we link proteolytic ubiquitylation with post‐transcriptional regulation and nominate OTUD6B as a potential mediator of the MGUS‐multiple myeloma transition, a central regulator of MYC, and an actionable vulnerability in multiple myeloma and other tumors with an activated OTUD6B‐LIN28B axis."
36059274
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"First, we confirmed specific bi‐directional binding between LIN28B and OTUD6B using different members of the OTU DUB family as controls (Fig EV3D and E)."
36059274
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"To this end, we compared binding of OTUD6B to LIN28B in G1/S synchronized MM1.S cells and cells released from the cell cycle block."
36059274
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"These experiments revealed that binding of OTUD6B to LIN28B specifically occurs at G1/S (Fig 3A)."
36059274
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"We next investigated whether LIN28B is a G1/S‐specific deubiquitylation substrate of OTUD6B. To this end, we compared binding of OTUD6B to LIN28B in G1/S synchronized MM1."
36059274
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"These experiments revealed that binding of OTUD6B to LIN28B specifically occurs at G1/S (Fig  xref )."
36059274
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"Given the strong implication of the OTUD6B‐LIN28B axis in cell cycle progression, we next performed in vivo xenograft experiments with human MM cells to further validate this nexus as a central vulnerability in MM."
36059274
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"These data distinguish the OTUD6B‐LIN28B DUB‐substrate pair as central dependency in MM cells in vitro and in vivo ."
36059274
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"To understand how the OTUD6B‐LIN28B axis regulates the G1/S‐transition, we performed RNA‐Seq experiments in MM cells, which were transduced with shRNAs against OTUD6B, LIN28B or respective controls."
36059274
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"Strikingly, we found a significant downregulation of prominent MYC targets (Mootha et al ,  xref ; Subramanian et al ,  xref ) in OTUD6B and LIN28B depleted MM cells, suggesting a direct impact of the OTUD6B‐LIN28B axis on MYC expression and activity (Fig  xref , and Appendix Fig  xref A)."
36059274
OTUD6B deubiquitinates LIN28B.
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OTUD6B deubiquitinates LIN28B. 5 / 5
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"Although OTUD6B regulates pVHL independently of its DUB activity (Liu et al, 2020), the catalytic cysteine of OTUD6B is required to limit ubiquitination of β-TrCP (Li et al, 2023) and LIN28B (Paulmann et al, 2022), as we found for KIFC1 (Fig. 6C)."
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"Specificity of this deubiquitylation event was ascertained by overexpression of the catalytic inactive OTUD6B mutant (C158A), which deubiquitylated LIN28B to a substantially smaller extent (Fig 2C)."
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"OTUD6B readily deubiquitylated LIN28B in this in vitro reconstituted system, suggesting that LIN28B is a direct substrate (Fig 2E)."
36059274
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"Together, these data suggest that LIN28B is a cell cycle regulated protein with highest abundance at the G1/S transition and early S‐phase and that OTUD6B specifically deubiquitylates LIN28B at the G1/S transition of the cell cycle to procure its stability."
36059274
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"Together, these data suggest that MCTS1 can enhance the stability of LIN28B during the G1/S transition by interacting with OTUD6B.Using a ubiquitin-K48 specific antibody, we observed lentivirus-mediat[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
37634410
OTUD6B leads to the deubiquitination of LIN28B on E3. 1 / 1
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"In comparison, shRNA-mediated knockdown of OTUD6B drastically increased the polyubiquitination of endogenous LIN28B ( Fig. 3 E)."
37634410
OTUD6B ubiquitinates LIN28B.
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OTUD6B leads to the ubiquitination of LIN28B. 1 / 1
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"Indeed, siRNA‐mediated knockdown of OTUD6B substantially enhanced polyubiquitylation of LIN28B (Fig 2B), whereas forced expression of OTUD6B decreased LIN28B ubiquitylation (Figs 2C and EV4A)."
36059274
OTUD6B activates LIN28B.
| 1
OTUD6B activates LIN28B. 1 / 1
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"In the current study, we observed that MCTS1 could alter OTUD6B-mediated LIN28B stabilization in the G1/S transition of in LSCC cells."
37634410
OTUD6B affects VHL
4 | 9 18
OTUD6B binds VHL.
4 | 4 17
OTUD6B binds VHL. 10 / 23
4 | 4 15
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"Here, we tested the interaction between OTUD6B with pVHL mutants."
35110537
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"Otud6b can directly bind pVHL, reduce pVHL ubiquitination and proteasome degradation, and reduce HIF-1α accumulation in HCC cells under hypoxia conditions."
38878112
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"In addition, OTUD6B depletion reduced the inhibitory effects of ectopic pVHL missense mutants on cell migration and HIF-2α level, except for pVHL I151T. Thus, we speculated that I151 residue might be one of key sites of pVHL binding to OTUD6B. These results suggested that OTUD6B is an important regulator for the stability of pVHL missense mutants, which provides a potential therapeutic strategy for ccRCC with VHL mutations."
35110537
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"Thus, we speculated that I151 residue might be one of key sites of pVHL binding to OTUD6B."
35110537
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"Mechanistically, OTUD6B directly interacts with pVHL and enhances its stability."
35875077
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"The results showed that ectopic OTUD6B interacted with indicated pVHL mutants in HEK293 cells, but compared with pVHL wild type and the majority of mutants, the binding between pVHL I151T mutant with OTUD6B was markedly weakened (Fig. xref )."
35110537
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"At the same time, we observed that OTUD6B depletion reduced the inhibitory effects of pVHL wild-type and the mutants on cell migration and HIF-2α level, except for pVHL 151T mutant (Fig. xref a and b), suggesting that I151 residue might be one of key sites of pVHL binding to OTUD6B."
35110537
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"Indeed, further biochemical studies showed that, OTUD6B binds directly with pVHL rather than HIF-1α."
32323143
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"In addition, why does pVHL only bind with OTUD6B but not other OTU family members, such as OTUD6A?"
32323143
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"OTUD6B Interacts with pVHL."
32328410
OTUD6B binds cbc and VHL. 2 / 2
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"We used gel filtration chromatography assay to analyze the CBC VHL complex binding of OTUD6B. As shown in Figure xref and Figure S5F (Supporting Information), OTUD6B was detected in the same fractions with pVHL, elongin B, and elongin C, indicating that OTUD6B might be a component of CBC VHL complex."
32328410
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"In this proposed model, OTUD6B is a direct transcriptional target of HIF‐1α, and HIF‐1α is a direct ubiquitylation and degradation target of OTUD6B‐CBC VHL complex."
32328410
OTUD6B inhibits VHL.
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OTUD6B inhibits VHL. 2 / 2
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"In addition, OTUD6B depletion reduced the inhibitory effects of ectopic pVHL missense mutants on cell migration and HIF-2α level, except for pVHL I151T."
35110537
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"For instance, OTUD6B depletion also enhances cell migration and HIF-2α levels in a pVHL (Von Hippel-Lindau protein with missense point mutations)-dependent manner in clear cell renal cell carcinoma (ccRCC) [52]."
37752518
OTUD6B deubiquitinates VHL.
| 2
OTUD6B deubiquitinates VHL. 2 / 2
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"However, Otud6b limits ubiquitination of pVHL independently of its deubiquitase activity."
38878112
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"Moreover, mutant forms of OTUD6B with deletion of OTU domain or mutating the putative catalytic active sites could still suppress the ubiquitination of pVHL, which is consistent with previous report showing that OTUD6B is incapable of cutting any di-ubiquitin in vitro (Mevissen et al., 2013)."
32323143
OTUD6B ubiquitinates VHL.
| 1
OTUD6B ubiquitinates VHL. 1 / 1
| 1
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"Additionally, we observed that shRNA targeting OTUD6B increased pVHL ubiquitylation (Figure xref ), and ectopic expression of OTUD6B suppressed pVHL ubiquitylation induced by WSB1 in cells (Figure xref )."
32328410
OTUD6B activates VHL.
| 1
OTUD6B activates VHL. 1 / 1
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"Hence, these data suggest that as a transcriptional target gene of HIF, OTUD6B expression could be induced under the hypoxic condition to stabilize pVHL and promote the degradation of HIF-1α, thus forming a negative feedback loop in regulating HIF activity and oxygen sensing homeostasis.Taken together, this work reveals a new layer of molecular mechanism for the stability regulation of the pVHL tumor suppressor and reveals its potential clinical importance in HCC metastasis and treatment."
32323143
LIN28B affects OTUD6B
7 | 6 14
LIN28B binds OTUD6B.
7 | 5 14
OTUD6B binds LIN28B. 10 / 26
7 | 5 14
sparser
"Thus, we link proteolytic ubiquitylation with post‐transcriptional regulation and nominate OTUD6B as a potential mediator of the MGUS‐multiple myeloma transition, a central regulator of MYC, and an actionable vulnerability in multiple myeloma and other tumors with an activated OTUD6B‐LIN28B axis."
36059274
reach
"First, we confirmed specific bi‐directional binding between LIN28B and OTUD6B using different members of the OTU DUB family as controls (Fig EV3D and E)."
36059274
reach
"To this end, we compared binding of OTUD6B to LIN28B in G1/S synchronized MM1.S cells and cells released from the cell cycle block."
36059274
reach
"These experiments revealed that binding of OTUD6B to LIN28B specifically occurs at G1/S (Fig 3A)."
36059274
sparser
"We next investigated whether LIN28B is a G1/S‐specific deubiquitylation substrate of OTUD6B. To this end, we compared binding of OTUD6B to LIN28B in G1/S synchronized MM1."
36059274
sparser
"These experiments revealed that binding of OTUD6B to LIN28B specifically occurs at G1/S (Fig  xref )."
36059274
sparser
"Given the strong implication of the OTUD6B‐LIN28B axis in cell cycle progression, we next performed in vivo xenograft experiments with human MM cells to further validate this nexus as a central vulnerability in MM."
36059274
sparser
"These data distinguish the OTUD6B‐LIN28B DUB‐substrate pair as central dependency in MM cells in vitro and in vivo ."
36059274
sparser
"To understand how the OTUD6B‐LIN28B axis regulates the G1/S‐transition, we performed RNA‐Seq experiments in MM cells, which were transduced with shRNAs against OTUD6B, LIN28B or respective controls."
36059274
sparser
"Strikingly, we found a significant downregulation of prominent MYC targets (Mootha et al ,  xref ; Subramanian et al ,  xref ) in OTUD6B and LIN28B depleted MM cells, suggesting a direct impact of the OTUD6B‐LIN28B axis on MYC expression and activity (Fig  xref , and Appendix Fig  xref A)."
36059274
LIN28B inhibits OTUD6B.
| 1
LIN28B inhibits OTUD6B. 1 / 1
| 1
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"Likewise, the reduction in cell proliferation was not further enhanced by a dual knockdown of LIN28B and OTUD6B (Fig 5F), while doxycycline induced re‐expression of LIN28B partially restored MYC mRNA‐levels in OTUD6B depleted MM cells (Appendix Fig S5D)."
36059274
VHL affects OTUD6B
4 | 4 17
OTUD6B binds VHL. 10 / 23
4 | 4 15
sparser
"Here, we tested the interaction between OTUD6B with pVHL mutants."
35110537
sparser
"Otud6b can directly bind pVHL, reduce pVHL ubiquitination and proteasome degradation, and reduce HIF-1α accumulation in HCC cells under hypoxia conditions."
38878112
sparser
"In addition, OTUD6B depletion reduced the inhibitory effects of ectopic pVHL missense mutants on cell migration and HIF-2α level, except for pVHL I151T. Thus, we speculated that I151 residue might be one of key sites of pVHL binding to OTUD6B. These results suggested that OTUD6B is an important regulator for the stability of pVHL missense mutants, which provides a potential therapeutic strategy for ccRCC with VHL mutations."
35110537
reach
"Thus, we speculated that I151 residue might be one of key sites of pVHL binding to OTUD6B."
35110537
sparser
"Mechanistically, OTUD6B directly interacts with pVHL and enhances its stability."
35875077
sparser
"The results showed that ectopic OTUD6B interacted with indicated pVHL mutants in HEK293 cells, but compared with pVHL wild type and the majority of mutants, the binding between pVHL I151T mutant with OTUD6B was markedly weakened (Fig. xref )."
35110537
sparser
"At the same time, we observed that OTUD6B depletion reduced the inhibitory effects of pVHL wild-type and the mutants on cell migration and HIF-2α level, except for pVHL 151T mutant (Fig. xref a and b), suggesting that I151 residue might be one of key sites of pVHL binding to OTUD6B."
35110537
reach
"Indeed, further biochemical studies showed that, OTUD6B binds directly with pVHL rather than HIF-1α."
32323143
reach
"In addition, why does pVHL only bind with OTUD6B but not other OTU family members, such as OTUD6A?"
32323143
sparser
"OTUD6B Interacts with pVHL."
32328410
OTUD6B binds cbc and VHL. 2 / 2
| 2
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"We used gel filtration chromatography assay to analyze the CBC VHL complex binding of OTUD6B. As shown in Figure xref and Figure S5F (Supporting Information), OTUD6B was detected in the same fractions with pVHL, elongin B, and elongin C, indicating that OTUD6B might be a component of CBC VHL complex."
32328410
sparser
"In this proposed model, OTUD6B is a direct transcriptional target of HIF‐1α, and HIF‐1α is a direct ubiquitylation and degradation target of OTUD6B‐CBC VHL complex."
32328410
OTUD6B affects IRF3
2 | 1 13 7
OTUD6B binds IRF3.
2 | 7
IRF3 binds OTUD6B. 6 / 8
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"Moreover, endogenous OTUD6B and IRF3 constitutively interacted in 293T cells ( xref )."
37650650
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"Through immunoprecipitation experiments, we found that OTUD6B interacted with the IRF3 C-terminal domain (IRF3-ΔN), and not with the N-terminal domain (IRF3-ΔC), suggesting that OTUD6B catalyzing site(s) are distributed in the C-terminal of IRF3 ( xref )."
37650650
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"Mechanically, we found that OTUD6B interacts with IRF3 and directly hydrolyzes both the lysine 11 (K11)- and the lysine 33 (K33)-linked polyubiquitin chain, but only K33-linked polyubiquitin at Lys315 of IRF3 is responsible for IRF3 proteasome degradation."
37650650
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"The OTUD6B interacts with IRF3 and cleaves K11- and K33-linked ubiquitin chains of IRF3."
37650650
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"OTUD6B interacted with IRF3."
37650650
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"Immunoprecipitation experiments confirmed that OTUD6B interacted with IRF3 and not with RIG-I, MAVS, and TBK1 ( xref ), and similar results were obtained using reverse immunoprecipitation ( xref )."
37650650
OTUD6B binds IRF3 and IRF7. 1 / 1
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"Further assays indicate that otud6b interacts with irf3 and irf7 and diminishes traf6-mediated K63-linked polyubiquitination of irf3 and irf7."
34183367
OTUD6B deubiquitinates IRF3.
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OTUD6B deubiquitinates IRF3. 4 / 4
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"These findings uncover that human OTUD6B can deubiquitinate and stabilize IRF3 and enhance type I IFN antiviral immunity."
37650650
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"Our results showed that overexpression of OTUD6B, and not defective OTUD6B-C57S, dramatically attenuated the ubiquitination levels of exogenously expressed IRF3, demonstrating that OTUD6B does reduce IRF3 ubiquitination levels and its deubiquitinase activity is critical (Fig. 5C)."
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"Human OTUD6B positively regulates type I IFN antiviral innate immune responses by deubiquitinating and stabilizing IRF3."
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"In contrast, OTUD6B knockdown enhanced IRF3 ubiquitination modification levels (Fig. 5D)."
37650650
OTUD6B leads to the deubiquitination of IRF3 on K315. 2 / 2
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"OTUD6B decreased IRF3 ubiquitination at the Lys315 residue."
37650650
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"Collectively, these findings demonstrated that OTUD6B inhibits IRF3 ubiquitination at Lys315."
37650650
OTUD6B ubiquitinates IRF3.
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OTUD6B leads to the ubiquitination of IRF3. 3 / 3
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"To investigate the type of ubiquitin chain that IRF3 OTUD6B cleaves, we analyzed the type(s) of IRF3 polyubiquitination mediated by OTUD6B."
37650650
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"Our results showed that overexpression of OTUD6B, and not defective OTUD6B-C57S, dramatically attenuated the ubiquitination levels of exogenously expressed IRF3, demonstrating that OTUD6B does reduce IRF3 ubiquitination levels and its deubiquitinase activity is critical (Fig. 5C)."
37650650
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"Zebrafish otud6b Negatively Regulates Antiviral Responses by Suppressing K63-Linked Ubiquitination of irf3 and irf7."
34183367
OTUD6B increases the amount of IRF3.
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OTUD6B increases the amount of IRF3. 2 / 2
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"OTUD6B knockdown strongly downregulated cellular IRF3 protein levels but not IRF3 mRNA level (Fig. 5A)."
37650650
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"Our results showed that overexpression of OTUD6B, and not defective OTUD6B-C57S, dramatically attenuated the ubiquitination levels of exogenously expressed IRF3, demonstrating that OTUD6B does reduce IRF3 ubiquitination levels and its deubiquitinase activity is critical (Fig. 5C)."
37650650
OTUD6B decreases the amount of IRF3.
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OTUD6B decreases the amount of IRF3. 2 / 2
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"Our results showed that overexpression of OTUD6B, and not defective OTUD6B-C57S, dramatically attenuated the ubiquitination levels of exogenously expressed IRF3, demonstrating that OTUD6B does reduce IRF3 ubiquitination levels and its deubiquitinase activity is critical (Fig. 5C)."
37650650
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"In contrast, OTUD6B knockdown enhanced IRF3 ubiquitination modification levels (Fig. 5D)."
37650650
OTUD6B activates IRF3.
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OTUD6B activates IRF3. 1 / 1
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"In the present study, we found that human deubiquitinase OTUD6B positively regulates IRF3-mediated antiviral immune response."
37650650
OTUD6B affects RIPK1
| 10 7
OTUD6B binds RIPK1.
| 6 7
OTUD6B binds RIPK1. 10 / 13
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"OTUD6B can bind to RIPK1, reduce its ubiquitination level and increase its protein stability."
38880876
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"Additionally, OTUD6B can bind to RIPK1, reduce its ubiquitination level and increase its protein stability."
38880876
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"These results indicated that OTUD6B can bind to RIPK1, reduce its ubiquitination level and increase its protein stability."
38880876
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"Finally, we verified the interaction between OTUD6B and RIPK1 by performing exogenous and endogenous two-way co-immunoprecipitation (CO-IP) (Fig.  xref G–K)."
38880876
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"In our study, the interaction between the deubiquitinating enzyme OTUD6B and RIPK1 was detected by IP mass spectrometry, and the interaction between OTUD6B and RIPK1 was subsequently evaluated via endogenous and exogenous co-IP."
38880876
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"OTUD6B can bind to RIPK1, reduce its ubiquitination level and increase its protein stability."
38880876
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"Finally, an increase in the protein degradation rate confirmed that OTUD6B can bind to RIPK1, reduce its ubiquitination level and increase its protein stability."
38880876
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"Additionally, OTUD6B can bind to RIPK1, reduce its ubiquitination level and increase its protein stability."
38880876
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"Then, we used co-immunoprecipitation (IP) experiments to determine which proteins interact with OTUD6B in LUAD cells, and the results showed that RIPK1 can interact with OTUD6B in LUAD cells (Fig.  xref C, D)."
38880876
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"Finally, we verified the interaction between OTUD6B and RIPK1 by performing exogenous and endogenous two-way co-immunoprecipitation (CO-IP) (Fig. 5G–K)."
38880876
OTUD6B activates RIPK1.
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OTUD6B activates RIPK1. 3 / 3
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"These findings also provide strong evidence that the deubiquitinated protein OTUD6B promotes the malignant progression of LUAD by increasing the stability of the RIPK1 protein."
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"The deubiquitinating protein OTUD6B promotes lung adenocarcinoma progression by stabilizing RIPK1."
38880876
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"In lung adenocarcinoma, the deubiquitinated protein OTUD6B promotes tumor progression by stabilizing RIPK1 [46]."
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OTUD6B increases the amount of RIPK1.
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OTUD6B increases the amount of RIPK1. 1 / 1
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"By stabilizing the protein level of RIPK1, OTUD6B promotes the progression of LUAD."
38880876
OTUD6B affects KIFC1
| 16 1
OTUD6B increases the amount of KIFC1.
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OTUD6B increases the amount of KIFC1. 6 / 6
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"As initial validation, transfection with these siRNA pools was repeated once more, confirming that depletion of USP3, OTUD6B, JOSD2, or UCHL1 decreased KIFC1 protein levels (Fig. 1E)."
39789388
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"OTUD6B modulates KIFC1 level and centrosome clustering in panel of breast cell lines."
39789388
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"The immortalised breast epithelial cell line hTERT-HME1 was used as a normal tissue comparator that has low centrosome amplification (Fig. EV1A) but, as in TNBC, OTUD6B depletion leads to reduced KIFC1 levels (Fig. EV2G)."
39789388
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"Together, these findings highlight OTUD6B as a DUB that maintains KIFC1 levels to ensure supernumerary centrosomes remain clustered, allowing cancer cells to avoid mitotic catastrophe and complete cell division.Amongst the 94 DUBs screened, we found that depletion of only OTUD6B or JOSD2 could both reduce cellular KIFC1 levels and increase multipolar spindles in TNBC cells (Figs."
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"This may also account for the observation that WT OTUD6B re-expression can rescue KIFC1 levels in interphase cells depleted of OTUD6B (Fig. 3D,E)."
39789388
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"Importantly, OTUD6B depletion could reduce KIFC1 expression in other cancer cell lines: MDA-MB-231, another TNBC cell line with moderate centrosome amplification, U2OS osteosarcoma cells that were originally used to demonstrate KIFC1 ubiquitination by the APC/C (Min et al, 2014), as well as in hTERT-HME1 as a model of immortalised normal breast epithelium (Fig. EV2E–G)."
39789388
OTUD6B deubiquitinates KIFC1.
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OTUD6B leads to the deubiquitination of KIFC1. 5 / 5
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"Whilst modulating OTUD6B had little effect on KIFC1 stability or ubiquitination in interphase cells (Fig. EV5I,J), acute ubiquitination of KIFC1 during mitosis (Appendix Fig. S7D) was decreased by overexpression of catalytically active OTUD6B (Fig. 6C) and increased by OTUD6B depletion (Fig. 6B) particularly for K11 polyubiquitin (Fig. 6E)."
39789388
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"This evidence for catalytic activity of OTUD6B towards K11-linked ubiquitin in other contexts is consistent with its ability to reduce mitotic KIFC1 polyubiquitination (Fig. 6) as the APC/C appends K11-linked and branched chains to substrates (Jin et al, 2008; Meyer and Rape, 2014)."
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"We speculate that such a mechanism may enable cancer cells to maintain a check on KIFC1 ubiquitylation during anaphase and telophase, to ensure that supernumerary centrosomes remain clustered so that chromosomes are accurately divided into daughter cells.However, we found that OTUD6B depletion could increase KIFC1 polyubiquitination not only at mitotic exit, but also in prometaphase arrested cells (Fig. 6B) when it had the strongest effect on KIFC1 degradation."
39789388
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"In the converse experiment, we found that overexpression of wild-type, but not catalytic dead, OTUD6B could decrease polyubiquitination of GFP-KIFC1 during mitotic exit (Fig. 6C)."
39789388
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"Importantly, the polyubiquitination of GFP-KIFC1 in the presence of K11-only ubiquitin was robustly increased by OTUD6B depletion (Fig. 6E)."
39789388
OTUD6B activates KIFC1.
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OTUD6B activates KIFC1. 4 / 4
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"We next asked whether this OTUD6B depletion phenotype was dependent on its effects on KIFC1 levels, and therefore could be rescued by overexpressing KIFC1."
39789388
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"We confirmed that OTUD6B depletion reduced KIFC1 in the population of uninduced cells, but that this was overcome by acute induction of KIFC1 with doxycycline (Fig. 3H,I)."
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"This observation is consistent with OTUD6B promoting KIFC1 centrosome clustering activity early in mitosis to form a pseudo-bipolar spindle, along with an ongoing requirement to maintain KIFC1 levels and prevent de-clustering during anaphase."
39789388
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"This is consistent with a model where OTUD6B modulates KIFC1 accumulation in early mitosis, when supernumerary centrosome clustering is initially required for spindle formation."
39789388
OTUD6B ubiquitinates KIFC1.
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OTUD6B leads to the ubiquitination of KIFC1. 1 / 1
| 1
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"We found that OTUD6B co-localises with KIFC1 on the mitotic spindle, interacts with KIFC1 via its N-terminal substrate binding domain, and can modulate KIFC1 polyubiquitylation and protein levels in early and late mitosis."
39789388
OTUD6B binds KIFC1.
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KIFC1 binds OTUD6B. 1 / 1
| 1
sparser
"In common with these two substrates, KIFC1 interacts with the N-terminus of OTUD6B (Fig.  xref ) (Li et al, xref ; Paulmann et al, xref )."
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OTUD6B activates cell population proliferation. 10 / 11
| 11
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"Our results revealed that knockdown of OTUD6B significantly impaired the viability, clonal expansion, and proliferation of LUAD cells (Fig. 2C–G)."
38880876
reach
"One study found that OTUD6B drives the G1/S transition and promotes the proliferation of multiple myeloma cells by suppressing microRNA biogenesis via LIN28B stabilization [ 11 ]."
37634410
reach
"Using nude mice and AMC–HN–8 as the representative cell lines, we explored how OTUD6B modulated in vivo proliferation of the tumor cells."
37634410
reach
"In CCA cells, OTUD6B knockdown reduced CCA cell proliferation and promoted apoptosis."
39192576
reach
"In the current study, using AMC–HN–8 and TU177 cells as representative LSCC models, we confirmed that OTUD6B overexpression enhanced the proliferation of LSCC in vitro and in vivo ."
37634410
reach
"In addition, lung cancer cell lines with OTUD6B knockdown significantly inhibited proliferation and invasion ability of lung cancer cells."
36052059
reach
"It is also obvious that OTUD6B silencing inhibited the proliferation, migration, and invasion of A549 and Pc9 cells ( Figures 10C–E )."
36052059
reach
"OTUD6B knockdown inhibited the proliferation of LUAD cells and enhanced apoptosis and inhibited metastasis in LUAD cells suppressed."
38880876
reach
"We found that activation of Otud6b expression with rOtud6b increased endothelial cell inflammation and apoptosis, smooth muscle cells inflammation and proliferation."
38878112
reach
"OTUD6B knockdown inhibited the proliferation of LUAD cells."
38880876
reach
"In normal and transformed cells, the expression of the OTUD6B isoform that represses protein synthesis and proliferation is quantitatively higher."
27864334
reach
"Further, lncRNA OTUD6B can inhibit ccRCC cell proliferation by suppressing the Wnt and beta-catenin pathway and the expressions of epithelial-to-mesenchymal transition related proteins."
33692953
reach
"The ability of OTUD6B to inhibit tumor proliferation was further verified in vivo in a nude mouse model ( Figure 10F )."
36052059
RIPK1 affects OTUD6B
| 6 7
OTUD6B binds RIPK1. 10 / 13
| 6 7
reach
"OTUD6B can bind to RIPK1, reduce its ubiquitination level and increase its protein stability."
38880876
sparser
"Additionally, OTUD6B can bind to RIPK1, reduce its ubiquitination level and increase its protein stability."
38880876
reach
"These results indicated that OTUD6B can bind to RIPK1, reduce its ubiquitination level and increase its protein stability."
38880876
sparser
"Finally, we verified the interaction between OTUD6B and RIPK1 by performing exogenous and endogenous two-way co-immunoprecipitation (CO-IP) (Fig.  xref G–K)."
38880876
sparser
"In our study, the interaction between the deubiquitinating enzyme OTUD6B and RIPK1 was detected by IP mass spectrometry, and the interaction between OTUD6B and RIPK1 was subsequently evaluated via endogenous and exogenous co-IP."
38880876
sparser
"OTUD6B can bind to RIPK1, reduce its ubiquitination level and increase its protein stability."
38880876
sparser
"Finally, an increase in the protein degradation rate confirmed that OTUD6B can bind to RIPK1, reduce its ubiquitination level and increase its protein stability."
38880876
reach
"Additionally, OTUD6B can bind to RIPK1, reduce its ubiquitination level and increase its protein stability."
38880876
sparser
"Then, we used co-immunoprecipitation (IP) experiments to determine which proteins interact with OTUD6B in LUAD cells, and the results showed that RIPK1 can interact with OTUD6B in LUAD cells (Fig.  xref C, D)."
38880876
reach
"Finally, we verified the interaction between OTUD6B and RIPK1 by performing exogenous and endogenous two-way co-immunoprecipitation (CO-IP) (Fig. 5G–K)."
38880876
OTUD6B affects PDLIM2
| 10 2
OTUD6B binds PDLIM2.
| 7 2
PDLIM2 binds OTUD6B. 9 / 9
| 7 2
reach
"Ji and colleagues 219 identified a circRNA called Hsa‐circ‐0003764 (circPTPN12) from the circRNA database, discovering its role in suppressing hepatocellular carcinoma progression by interacting with the PDZ domain of PDLIM2, promoting P65 ubiquitination and the assembly of the PDLIM2/OTUD6B complex, thereby highlighting the ESRP1/circPTPN12/PDLIM2/NF‐κB axis as a potential therapeutic target."
39525953
sparser
"Consistently, a Co-IP assay revealed the binding of OTUD6B to PDLIM2 (Fig.  xref A)."
38992675
reach
"Furthermore, circPTPN12 bolstered the assembly of the PDLIM2/OTUD6B complex by promoting the deubiquitination of PDLIM2."
38992675
sparser
"To investigate the role of circPTPN12 in this context, we conducted immunoprecipitation experiments and observed reduced binding of PDLIM2 and OTUD6B upon circPTPN12 knockdown, whereas overexpression of circPTPN12 resulted in increased binding of PDLIM2 and OTUD6B. We discovered that circPTPN12 serves as a scaffold, facilitating the interaction between PDLIM2 and OTUD6B, promoting PDLIM2 deubiquitination, maintaining its expression, and exerting its anti-cancer function."
38992675
reach
"Consistently, a Co-IP assay revealed the binding of OTUD6B to PDLIM2 (Fig. 5A)."
38992675
reach
"RNA pull-down assays confirmed the association between PDLIM2, OTUD6B and circPTPN12 (Fig. 5C)."
38992675
reach
"Additionally, the Co-immunoprecipitation (Co-IP) assay showed a decrease in the binding between OTUD6B and PDLIM2 in circPTPN12 knockdown cells compared to control cells."
38992675
reach
"To investigate the role of circPTPN12 in this context, we conducted immunoprecipitation experiments and observed reduced binding of PDLIM2 and OTUD6B upon circPTPN12 knockdown, whereas overexpression of circPTPN12 resulted in increased binding of PDLIM2 and OTUD6B."
38992675
reach
"We discovered that circPTPN12 serves as a scaffold, facilitating the interaction between PDLIM2 and OTUD6B, promoting PDLIM2 deubiquitination, maintaining its expression, and exerting its anti-cancer function.The regulation of circRNA biogenesis is intricate."
38992675
OTUD6B ubiquitinates PDLIM2.
| 1
OTUD6B leads to the ubiquitination of PDLIM2. 1 / 1
| 1
reach
"Conversely, reducing OTUD6B levels and further enhancing the ubiquitination of PDLIM2 was observed upon circPTPN12 overexpression (Fig. 5J-K)."
38992675
OTUD6B increases the amount of PDLIM2.
| 1
OTUD6B increases the amount of PDLIM2. 1 / 1
| 1
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"The experimental results demonstrated that overexpressing OTUD6B notably increased PDLIM2 protein levels in HCC cells."
38992675
OTUD6B deubiquitinates PDLIM2.
| 1
OTUD6B leads to the deubiquitination of PDLIM2. 1 / 1
| 1
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"Immunoprecipitation (IP) results indicated that the knockdown of OTUD6B effectively enhanced the ubiquitylation of PDLIM2, while overexpression of OTUD6B decreased the ubiquitylation of PDLIM2 (Fig. 5F-G)."
38992675
IRF3 affects OTUD6B
2 | 1 7
IRF3 binds OTUD6B.
2 | 7
IRF3 binds OTUD6B. 6 / 8
2 | 6
sparser
"Moreover, endogenous OTUD6B and IRF3 constitutively interacted in 293T cells ( xref )."
37650650
sparser
"Through immunoprecipitation experiments, we found that OTUD6B interacted with the IRF3 C-terminal domain (IRF3-ΔN), and not with the N-terminal domain (IRF3-ΔC), suggesting that OTUD6B catalyzing site(s) are distributed in the C-terminal of IRF3 ( xref )."
37650650
sparser
"Mechanically, we found that OTUD6B interacts with IRF3 and directly hydrolyzes both the lysine 11 (K11)- and the lysine 33 (K33)-linked polyubiquitin chain, but only K33-linked polyubiquitin at Lys315 of IRF3 is responsible for IRF3 proteasome degradation."
37650650
sparser
"The OTUD6B interacts with IRF3 and cleaves K11- and K33-linked ubiquitin chains of IRF3."
37650650
sparser
"OTUD6B interacted with IRF3."
37650650
sparser
"Immunoprecipitation experiments confirmed that OTUD6B interacted with IRF3 and not with RIG-I, MAVS, and TBK1 ( xref ), and similar results were obtained using reverse immunoprecipitation ( xref )."
37650650
OTUD6B binds IRF3 and IRF7. 1 / 1
| 1
sparser
"Further assays indicate that otud6b interacts with irf3 and irf7 and diminishes traf6-mediated K63-linked polyubiquitination of irf3 and irf7."
34183367
IRF3 activates OTUD6B.
| 1
IRF3 activates OTUD6B. 1 / 1
| 1
reach
"Confocal microscopy showed that more IRF3 translocated to the nucleus with overexpressing OTUD6B upon viral infection as measured using mean fluorescence intensity (MFI), the MFI value changed from 8,965 to 11,260 (Fig. 4E and F)."
37650650
PDLIM2 affects OTUD6B
| 7 2
PDLIM2 binds OTUD6B. 9 / 9
| 7 2
reach
"Ji and colleagues 219 identified a circRNA called Hsa‐circ‐0003764 (circPTPN12) from the circRNA database, discovering its role in suppressing hepatocellular carcinoma progression by interacting with the PDZ domain of PDLIM2, promoting P65 ubiquitination and the assembly of the PDLIM2/OTUD6B complex, thereby highlighting the ESRP1/circPTPN12/PDLIM2/NF‐κB axis as a potential therapeutic target."
39525953
sparser
"Consistently, a Co-IP assay revealed the binding of OTUD6B to PDLIM2 (Fig.  xref A)."
38992675
reach
"Furthermore, circPTPN12 bolstered the assembly of the PDLIM2/OTUD6B complex by promoting the deubiquitination of PDLIM2."
38992675
sparser
"To investigate the role of circPTPN12 in this context, we conducted immunoprecipitation experiments and observed reduced binding of PDLIM2 and OTUD6B upon circPTPN12 knockdown, whereas overexpression of circPTPN12 resulted in increased binding of PDLIM2 and OTUD6B. We discovered that circPTPN12 serves as a scaffold, facilitating the interaction between PDLIM2 and OTUD6B, promoting PDLIM2 deubiquitination, maintaining its expression, and exerting its anti-cancer function."
38992675
reach
"Consistently, a Co-IP assay revealed the binding of OTUD6B to PDLIM2 (Fig. 5A)."
38992675
reach
"RNA pull-down assays confirmed the association between PDLIM2, OTUD6B and circPTPN12 (Fig. 5C)."
38992675
reach
"Additionally, the Co-immunoprecipitation (Co-IP) assay showed a decrease in the binding between OTUD6B and PDLIM2 in circPTPN12 knockdown cells compared to control cells."
38992675
reach
"To investigate the role of circPTPN12 in this context, we conducted immunoprecipitation experiments and observed reduced binding of PDLIM2 and OTUD6B upon circPTPN12 knockdown, whereas overexpression of circPTPN12 resulted in increased binding of PDLIM2 and OTUD6B."
38992675
reach
"We discovered that circPTPN12 serves as a scaffold, facilitating the interaction between PDLIM2 and OTUD6B, promoting PDLIM2 deubiquitination, maintaining its expression, and exerting its anti-cancer function.The regulation of circRNA biogenesis is intricate."
38992675
MCTS1 affects OTUD6B
3 | 4 2
MCTS1 binds OTUD6B.
3 | 2 2
OTUD6B binds MCTS1. 4 / 7
3 | 2 2
reach
"In this study, we further explored the expression of potential interaction between MCTS1 and OTUD6B and its influence on the ubiquitination and degradation of OTUD6B's substrate in LSCC.Data extractio[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
37634410
sparser
"In this study, we found a novel interaction between MCTS1 and OTUD6B-1."
37634410
sparser
"In this study, we further explored the expression of potential interaction between MCTS1 and OTUD6B and its influence on the ubiquitination and degradation of OTUD6B's substrate in LSCC."
37634410
reach
"Bioinformatics prediction using GENEMANIA ( http://genemania.org/ ) [ 14 ] and BioGRID ( https://thebiogrid.org/ ) [ 15 ] both suggested a potential binding between MCTS1 and OTUD6B."
37634410
MCTS1 activates OTUD6B.
| 2
MCTS1 activates OTUD6B. 2 / 2
| 2
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"MCTS1 enhances OTUD6B-mediated cleaving of K48-branched ubiquitin chains from LIN28B, thereby increasing LIN28B stability."
37634410
reach
"These findings imply that MCTS1 enhances OTUD6B-mediated cleaving of K48-branched ubiquitin chains from LIN28B, which determines the proteolytic substrate fate ( Fig. 3 D and E)."
37634410
reach
"First, we found that mRNA level of OTUD6B in ESCC cells treated with ATRA did not change (Figure 6J), suggesting that ATRA may upregulate OTUD6B protein via regulating its translation."
37038094
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"Since RARα has been reported to repress the translation of specific mRNAs through binding with the untranslated region (UTR) of target mRNA, and this repression can be relieved by ATRA, 18 we tested whether ATRA promoted the translation of OTUD6B by relieving the binding of RARα to the UTR of OTUD6B mRNA."
37038094
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"Using a luciferase reporter containing 5’ UTR and 3’ UTR of OTUD6B (Figure 6M), we found that ATRA promotes the luciferase translation in a RARα‐dependent manner, confirming it recognizes OTUD6B mRNA and thus regulates its translation (Figure 6N)."
37038094
reach
"Importantly, all-trans retinoic acid (ATRA) is found to promote OTUD6B translation and thus suppress ESCC tumor growth and enhance the response of ESCC tumors to anti-PD-1 immunotherapies."
37038094
reach
"Importantly, all‐trans retinoic acid (ATRA) was found to promote the OTUD6B translation, suppress the tumorigenesis and metastasis of ESCC, and enhance the response of established ESCC tumors to anti‐PD‐1 immunotherapy."
37038094
All-trans-retinoic acid increases the amount of OTUD6B.
| 2
All-trans-retinoic acid increases the amount of OTUD6B. 2 / 2
| 2
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"Indeed, ATRA treatment significantly increased OTUD6B protein level in a dose‐dependent manner and showed little effect on OTUD6A or OTUD2 expression (Figure 6A and Figure S6A, Supporting Information)."
37038094
reach
"Taken together, these results showed that ATRA upregulated the protein level of OTUD6B in ESCC cells and inhibited their TIC properties.Interestingly, we noted that the effects of ATRA in suppressing TIC properties were diminished in OTUD6B‐knockdown cells (Figure 6B–F)."
37038094
All-trans-retinoic acid inhibits OTUD6B. 1 / 1
| 1
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"26b Here, we found that ATRA suppressed ESCC tumor initiation and progression by promoting OTUD6B translation and inhibiting TIC properties of ESCC cancer cells."
37038094
OTUD6B affects apoptotic process
| 1 7
OTUD6B activates apoptotic process.
| 5
reach
"In CCA cells, OTUD6B knockdown reduced CCA cell proliferation and promoted apoptosis."
39192576
reach
"In the hormone receptor positive cell line HCC1500 (ER positive) silencing STK39 decreased survival (p = 0.03) and silencing OTUD6B increased apoptosis (p = 0.02) (XREF_FIG and XREF_FIG)."
31126858
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"In the HER2 positive cell line SKBR3, silencing all three early stage antigens decreased survival (PDHX and STK39 p < 0.0001 and OTUD6B p = 0.05) and both STK39 and OTUD6B increased apoptosis (STK39 p = 0.0002 and OTUD6B p < 0.0001)."
31126858
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"Overexpressing Otud-6B in Ba/F3 cells resulted in downregulation of proliferation and increased the frequency of apoptosis [XREF_BIBR]."
31208841
reach
"OTUD6B knockdown inhibited the proliferation of LUAD cells and enhanced apoptosis and inhibited metastasis in LUAD cells suppressed."
38880876
OTUD6B inhibits apoptotic process.
| 1 2
eidos
"In the HER2 positive cell line SKBR3 , silencing all three early stage antigens decreased survival ( PDHX and STK39 p < 0.0001 and OTUD6B p =0 .05 ) and both STK39 and OTUD6B increased apoptosis ( STK39 p =0 .0002 and OTUD6B p < 0.0001 ) ."
31126858
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"OTUD6B knockdown enhanced apoptosis and inhibited metastasis in LUAD cells."
38880876
reach
"TUNEL staining revealed that knockdown of OTUD6B can induce apoptosis in LUAD cells (Fig. 2H, I)."
38880876
OTUD6B affects SNAI1
| 8
OTUD6B decreases the amount of SNAI1.
| 3
OTUD6B decreases the amount of SNAI1. 3 / 3
| 3
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"In support of the notion that OTUD6B enhances β‐TrCP protein stability and thus decreases SNAIL protein level, we found a significant positive correlation between OTUD6B and β‐TrCP protein levels in ESCC tissues (Figure 5C) and a negative correlation between OTUD6B and SNAIL protein levels (Figure 5D)."
37038094
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"Consistent with the notion that OTUD6B enhances β‐TrCP protein stability and decreases SNAIL protein level, ATRA treatment upregulated the level of β‐TrCP and downregulated the expression of SNAIL (Figure 6A)."
37038094
reach
"Knockdown of OTUD6B increases SNAIL expression through decreasing β‐TrCP protein stability, and accelerates ESCC tumor progression through the OTUD6B‐β‐TrCP‐SNAIL axis (Figure 7L)."
37038094
OTUD6B increases the amount of SNAI1.
| 2
OTUD6B increases the amount of SNAI1. 2 / 2
| 2
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"As expected, overexpression of OTUD6B increased, while knockdown of OTUD6B decreased, the ubiquitination level and degradation of SNAIL in ESCC cells (Figure 4D–G and Figure S4C–F, Supporting Information)."
37038094
reach
"Moreover, low OTUD6B expression is significantly correlated with decreased β‐TrCP and increased SNAIL protein level in ESCC tissues and predicts a poor prognosis in ESCC patients."
37038094
OTUD6B activates SNAI1.
| 2
OTUD6B activates SNAI1. 2 / 2
| 2
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"Thus, these results demonstrated that OTUD6B inhibited TIC properties of ESCC cells by decreasing SNAIL stability.2.5 Reduced OTUD6B Predicts a Poor Prognosis in Esophageal Squamous Cell Carcinoma Patients."
37038094
reach
"These results indicate that in an immune‐competent setting, OTUD6B still functions as an important tumor suppressor of ESCC development.2.4 OTUD6B Promotes the Degradation of SNAIL."
37038094
OTUD6B binds SNAI1.
| 1
OTUD6B binds SNAI1. 1 / 1
| 1
reach
"The results showed that OTUD6B could bind with SNAIL but not β‐catenin or IκBα (Figure 4C)."
37038094
OTUD6B affects OTUB1
5 | 3
OTUD6B binds OTUB1. 3 / 8
5 | 3
sparser
"Studying OTUD6B-OTUB1 Protein-Protein Interaction by Low-Throughput GFP-Trap Assays and High-Throughput AlphaScreen Assays."
33421002
sparser
"We describe the GFP-Trap immunoprecipitation as a cell-based method to analyze the OTUD6B-OTUB1 interaction in the cellular context and the AlphaScreen (amplified luminescent proximity homogeneous assay) assay as a tool to detect direct interactions and to search for PPI inhibitors."
33421002
sparser
"Meanwhile, in the present study we found that OTUD6B was closely associated with OTUB1, implying its potential role in immune response."
36052059
OTUD6B affects MCTS1
3 | 3 2
OTUD6B binds MCTS1.
3 | 2 2
OTUD6B binds MCTS1. 4 / 7
3 | 2 2
reach
"In this study, we further explored the expression of potential interaction between MCTS1 and OTUD6B and its influence on the ubiquitination and degradation of OTUD6B's substrate in LSCC.Data extractio[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
37634410
sparser
"In this study, we found a novel interaction between MCTS1 and OTUD6B-1."
37634410
sparser
"In this study, we further explored the expression of potential interaction between MCTS1 and OTUD6B and its influence on the ubiquitination and degradation of OTUD6B's substrate in LSCC."
37634410
reach
"Bioinformatics prediction using GENEMANIA ( http://genemania.org/ ) [ 14 ] and BioGRID ( https://thebiogrid.org/ ) [ 15 ] both suggested a potential binding between MCTS1 and OTUD6B."
37634410
OTUD6B increases the amount of MCTS1.
| 1
OTUD6B increases the amount of MCTS1. 1 / 1
| 1
reach
"However, OTUD6B or LIN28B shRNA only weakened but could not abrogate MCTS1 overexpression-induced cyclin D1 and c-Myc protein expression ( Fig. 4 B)."
37634410
OTUB1 affects OTUD6B
5 | 3
OTUD6B binds OTUB1. 3 / 8
5 | 3
sparser
"Studying OTUD6B-OTUB1 Protein-Protein Interaction by Low-Throughput GFP-Trap Assays and High-Throughput AlphaScreen Assays."
33421002
sparser
"We describe the GFP-Trap immunoprecipitation as a cell-based method to analyze the OTUD6B-OTUB1 interaction in the cellular context and the AlphaScreen (amplified luminescent proximity homogeneous assay) assay as a tool to detect direct interactions and to search for PPI inhibitors."
33421002
sparser
"Meanwhile, in the present study we found that OTUD6B was closely associated with OTUB1, implying its potential role in immune response."
36052059
OTUD6B affects Mice
| 7
OTUD6B activates Mice. 7 / 7
| 7
reach
"Otud6b deficiency inhibits PAH development in hypoxia mice models."
38878112
reach
"Furthermore, we found that human OTUD6B enhances type I IFN antiviral immune response in mice upon viral infection."
37650650
reach
"As shown in the figure, expressions of Calpain-1, Otud6b, and HIF-1α proteins were increased in hypoxia induced mice and HPAECs, while not seen in siOtud6b treated mice and HPAECs."
38878112
reach
"Thereafter, we intranasally infected OTUD6B-upregulated mice with VSV and found that IFN-β production was significantly increased in the lung tissue (Fig. 8B) and serum (Fig. 8C) of OTUD6B-upregulated mice compared with that in control vector-injected mice."
37650650
reach
"Consistently, ISG expression was higher in OTUD6B-upregulated mice (Fig. 8B), and less viral infection was detected in their lung tissue (Fig. 8D) and serum (Fig. 8E) than in control mice 3 days post infection."
37650650
reach
"When viral infection was extended to 10 days, survival results showed that OTUD6B-upregulated mice were more resistant to VSV infection than control vector-injected mice (Fig. 8F)."
37650650
reach
"Collectively, our data suggested that OTUD6B-upregulated mice possess a more potent type I IFN antiviral defense against VSV infection."
37650650
OTUD6B affects MYC
| 6 1
OTUD6B activates MYC.
| 3
OTUD6B activates MYC. 3 / 3
| 3
reach
"From a cell biological point of view, the OTUD6B‐LIN28B nexus links proteolytic ubiquitylation to mRNA biogenesis and eventually directs MYC activity to the G1/S cell cycle transition, a previously unappreciated crosstalk (Hildebrandt et al, 2017)."
36059274
reach
"OTUD6B activates MYC via LIN28B ."
36059274
reach
"Depletion of OTUD6B significantly reduced MYC mRNA and protein levels in various MM cell lines to a similar extent irrespective of the nature of MYC aberrations present in the individual lines (Fig 5C; Dib et al, 2008; Quentmeier et al, 2019)."
36059274
OTUD6B increases the amount of MYC.
| 2
OTUD6B increases the amount of MYC. 2 / 2
| 2
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"Simultaneous depletion of OTUD6B and LIN28B did not further reduce MYC expression compared with the single knockdowns, supporting the notion that LIN28B functions downstream of OTUD6B (Fig 5D and E)."
36059274
reach
"These data suggest that OTUD6B augments MYC protein expression via LIN28B and serves as a regulator of MYC by linking the UPS with post‐transcriptional control."
36059274
OTUD6B decreases the amount of MYC.
| 1
OTUD6B decreases the amount of MYC. 1 / 1
| 1
reach
"Strikingly, we found a significant downregulation of prominent MYC targets (Mootha et al, 2003; Subramanian et al, 2005) in OTUD6B and LIN28B depleted MM cells, suggesting a direct impact of the OTUD6B‐LIN28B axis on MYC expression and activity (Fig 5A and B, and Appendix Fig S4A)."
36059274
OTUD6B binds MYC.
| 1
OTUD6B binds MYC. 1 / 1
| 1
sparser
"We constructed overexpression plasmids Myc-UCHL-1, Myc-CPT1B, and Myc-OTUD6B. Then, these plasmids were co-transfected with Flag-Metrnl in HEK293T cell lines, respectively."
38745648
OTUD6B affects cell migration
| 6
OTUD6B inhibits cell migration. 6 / 6
| 6
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"Functionally, we revealed that OTUD6B depletion enhanced cell migration and HIF-2α level in ccRCC cells in a pVHL dependent manner."
35110537
reach
"Correction to: Deubiquitylase OTUD6B stabilizes the mutated pVHL and suppresses cell migration in clear cell renal cell carcinoma."
35650190
reach
"For instance, OTUD6B depletion also enhances cell migration and HIF-2α levels in a pVHL (Von Hippel-Lindau protein with missense point mutations)-dependent manner in clear cell renal cell carcinoma (ccRCC) [52]."
37752518
reach
"Deubiquitylase OTUD6B stabilizes the mutated pVHL and suppresses cell migration in clear cell renal cell carcinoma."
35110537
reach
"The deubiquitinase OTUD6B inhibits cell migration in clear cell renal cell carcinoma and hepatocellular carcinoma by stabilizing mutated pVHL [16]."
38880876
reach
"Consistent with this mechanism, over-expression of pVHL could antagonize OTUD6B depletion-induced effects in HCC cell migration and metastasis."
32323143
OTUD6B affects Neoplasms
| 6
OTUD6B activates Neoplasms.
| 4
OTUD6B activates Neoplasms. 4 / 4
| 4
reach
"Knockdown of OTUD6B in lung cancer cells inhibits tumor self-renewal."
36052059
reach
"OTUD6B knockdown suppressed LUAD tumor growth in a mouse model."
38880876
reach
"Although OTUD6B has been reported to promote tumor progression, the specific substrate OTUD6B, a member of the deubiquitinase family, has not been studied."
38880876
reach
"In lung adenocarcinoma, the deubiquitinated protein OTUD6B promotes tumor progression by stabilizing RIPK1 [46]."
40170095
OTUD6B inhibits Neoplasms.
| 2
OTUD6B inhibits Neoplasms. 2 / 2
| 2
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"The ability of OTUD6B to inhibit tumor proliferation was further verified in vivo in a nude mouse model ( Figure 10F )."
36052059
reach
"Collectively, these results suggest that OTUD6B functions as a bona fide DUB that directly targeting and stabilizing β‐TrCP.2.3 OTUD6B Reduces Tumor-Initiating Cell Properties of Esophageal Squamous Cell Carcinoma Cells via beta-TrCP."
37038094
OTUD6B activates Pulmonary Arterial Hypertension. 4 / 4
| 4
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"However, whether Calpain-1 is involved in Otud6b mediated PAH has not been reported in the literature.Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that is activated under hypoxia conditions and consists of β and α subunits [22]."
38878112
reach
"Otud6b deficiency inhibits PAH development in hypoxia mice models."
38878112
reach
"The knock-down effect of siOtud6b#1 is stronger than siOtud6b#2 and siOtud6b#3.To test whether the reduction of Otud6b inhibits PAH development, we targeted Otud6b (siOtud6b, GGGAATGAAGAACGCCGTT) and non-targeted control (siNC) modified anti-siRNA oligonucleotides by trachea infusion for 3 weeks."
38878112
reach
"Our study shows that increased Otud6b expression during hypoxia promotes the development of PAH models through a positive feedback loop between HIF-1alpha and Calpain-1."
38878112
reach
"The results showed that in both models, the expression of Otud6b in pulmonary vascular was upregulated, and in addition, Otud6b gene knock-down attenuated PAH development."
38878112
OTUD6B affects HIF1A
| 2 3
OTUD6B binds HIF1A.
| 3
OTUD6B binds HIF1A. 3 / 3
| 3
sparser
"However, OTUD6B did not bind to HIF-1α but instead directly bound to pVHL."
34201062
sparser
"Liu et al. showed that Otud6b can interact with HIF-1α to coordinate various cellular process responses under hypoxia."
38878112
sparser
"Through luciferase reporter assay and chromatin immunoprecipitation assay, the authors found that HIF-1α binds with the promoter of OTUD6B . Hence, these data suggest that as a transcriptional target gene of HIF, OTUD6B expression could be induced under the hypoxic condition to stabilize pVHL and promote the degradation of HIF-1α, thus forming a negative feedback loop in regulating HIF activity and oxygen sensing homeostasis."
32323143
OTUD6B activates HIF1A.
| 2
OTUD6B activates HIF1A. 2 / 2
| 2
reach
"Otud6b increases HPAECs production of HIF-1alpha, ET-1 and VEGF."
38878112
reach
"Otud6b induces pulmonary arterial hypertension by mediating the Calpain-1/HIF-1alpha signaling pathway."
38878112
OTUD6B affects PTK2
1 | 2 1
OTUD6B binds PTK2.
1 | 1
OTUD6B binds PTK2. 1 / 2
1 | 1
sparser
"It is possible that some of the OTUD6B-related features are partly a result of defective interaction between the OTUD6B and PTK2 genes."
| PMC
OTUD6B ubiquitinates PTK2.
| 1
OTUD6B ubiquitinates PTK2. 1 / 1
| 1
reach
"Our study demonstrates that OTUD6B knockdown participates in the ubiquitination of PTK2 and phosphorylation of STAT3 to alleviate the process of CCA."
39192576
OTUD6B deubiquitinates PTK2.
| 1
OTUD6B deubiquitinates PTK2. 1 / 1
| 1
reach
"Mechanistically, OTUD6B is involved in the deubiquitination of PTK2."
39192576
OTUD6B affects AS
| 4
AS binds OTUD6B. 3 / 3
| 3
sparser
"To confirm whether OTUD6B-AS knockdown exerts a tumour-inhibition role in viv o, we performed xenograft tumour experiment using nude mice."
32682012
sparser
"Plate colony formation assay showed that colony formation of MCF-7 cells decreased after silencing YTHDF3-AS1, LINC00839, and OTUD6B-AS and increased after silencing NIFK-AS1 and TOLLIP-AS1 ( xref )."
37529698
sparser
"Overall, these data confirm that OTUD6B-AS knockdown exerts a tumour-inhibition role in HCC in vivo ."
32682012
sparser
"In addition, the differential expression levels of lncRNAs included TSIX, NRIR, ncRNA00201, OTUD6B-AS, CTBP1-AS2, AGAP2-AS1, and HIFA-AS1, which can target mRNAs and might also involve pathogenesis and pathological changes in patients with SSc."
| PMC
HIF1A affects OTUD6B
| 1 3
HIF1A binds OTUD6B.
| 3
OTUD6B binds HIF1A. 3 / 3
| 3
sparser
"However, OTUD6B did not bind to HIF-1α but instead directly bound to pVHL."
34201062
sparser
"Liu et al. showed that Otud6b can interact with HIF-1α to coordinate various cellular process responses under hypoxia."
38878112
sparser
"Through luciferase reporter assay and chromatin immunoprecipitation assay, the authors found that HIF-1α binds with the promoter of OTUD6B . Hence, these data suggest that as a transcriptional target gene of HIF, OTUD6B expression could be induced under the hypoxic condition to stabilize pVHL and promote the degradation of HIF-1α, thus forming a negative feedback loop in regulating HIF activity and oxygen sensing homeostasis."
32323143
HIF1A increases the amount of OTUD6B.
| 1
HIF1A increases the amount of OTUD6B. 1 / 1
| 1
reach
"At the same time, we also found that blocking Calpain-1 reduced the effect of Otud6b on HIF-1alpha, and inhibiting HIF-1alpha reduced the expression of Calpain-1 and Otud6b."
38878112
AS affects OTUD6B
| 4
AS binds OTUD6B. 3 / 3
| 3
sparser
"To confirm whether OTUD6B-AS knockdown exerts a tumour-inhibition role in viv o, we performed xenograft tumour experiment using nude mice."
32682012
sparser
"Plate colony formation assay showed that colony formation of MCF-7 cells decreased after silencing YTHDF3-AS1, LINC00839, and OTUD6B-AS and increased after silencing NIFK-AS1 and TOLLIP-AS1 ( xref )."
37529698
sparser
"Overall, these data confirm that OTUD6B-AS knockdown exerts a tumour-inhibition role in HCC in vivo ."
32682012
sparser
"In addition, the differential expression levels of lncRNAs included TSIX, NRIR, ncRNA00201, OTUD6B-AS, CTBP1-AS2, AGAP2-AS1, and HIFA-AS1, which can target mRNAs and might also involve pathogenesis and pathological changes in patients with SSc."
| PMC
Cbc affects OTUD6B
| 3
OTUD6B binds cbc and VHL. 2 / 2
| 2
sparser
"We used gel filtration chromatography assay to analyze the CBC VHL complex binding of OTUD6B. As shown in Figure xref and Figure S5F (Supporting Information), OTUD6B was detected in the same fractions with pVHL, elongin B, and elongin C, indicating that OTUD6B might be a component of CBC VHL complex."
32328410
sparser
"In this proposed model, OTUD6B is a direct transcriptional target of HIF‐1α, and HIF‐1α is a direct ubiquitylation and degradation target of OTUD6B‐CBC VHL complex."
32328410
Cbc binds OTUD6B. 1 / 1
| 1
sparser
"In this proposed model, OTUD6B is a direct transcriptional target of HIF‐1α, and HIF‐1α is a direct ubiquitylation and degradation target of OTUD6B‐CBC VHL complex."
32328410
OTUD6B activates type I interferon production. 3 / 3
| 3
reach
"It was shown that IFN-β reporter luciferase activity was no longer enhanced by overexpressing IRF3/5D in the presence of OTUD6B (Fig. 4A), suggesting that OTUD6B might promote type I IFN production via IRF3."
37650650
reach
"Furthermore, we demonstrated that OTUD6B can promote type I IFN production and cellular antiviral responses in vivo, which may provide a potential target for enhancing type I IFN antiviral therapy in clinical settings."
37650650
reach
"OTUD6B promoted type I IFN production in response to viral infection."
37650650
reach
"Thus, unlike the previous report that zebrafish OTUD6B negatively regulates the antiviral response by suppressing K63-linked ubiquitination of IRF3 and IRF7, we demonstrate that human OTUD6B actually enhances type I IFN response and has the potential for antiviral therapy."
37650650
reach
"The function of OTUD6B in response to viral infection has rarely been reported, except that a recent study found that OTUD6B from zebrafish can negatively regulate the antiviral response by suppressing K63-linked ubiquitination of IRF3 and IRF7 (28)."
37650650
reach
"Over-expression of Otud6b in zebrafish attenuated induction of viral and chemical IFN signaling, whereas loss of otud6b strongly promoted the antiviral response."
35923854
OTUD6B affects cbc
| 3
OTUD6B binds cbc and VHL. 2 / 2
| 2
sparser
"We used gel filtration chromatography assay to analyze the CBC VHL complex binding of OTUD6B. As shown in Figure xref and Figure S5F (Supporting Information), OTUD6B was detected in the same fractions with pVHL, elongin B, and elongin C, indicating that OTUD6B might be a component of CBC VHL complex."
32328410
sparser
"In this proposed model, OTUD6B is a direct transcriptional target of HIF‐1α, and HIF‐1α is a direct ubiquitylation and degradation target of OTUD6B‐CBC VHL complex."
32328410
Cbc binds OTUD6B. 1 / 1
| 1
sparser
"In this proposed model, OTUD6B is a direct transcriptional target of HIF‐1α, and HIF‐1α is a direct ubiquitylation and degradation target of OTUD6B‐CBC VHL complex."
32328410
reach
"It is also obvious that OTUD6B silencing inhibited the proliferation, migration, and invasion of A549 and Pc9 cells ( Figures 10C–E )."
36052059
reach
"In addition, lung cancer cell lines with OTUD6B knockdown significantly inhibited proliferation and invasion ability of lung cancer cells."
36052059
reach
"In addition, in our transwell experiments, A549 and H1395 cells transfected with shOTUD6B lacked the ability to migrate to the lower chamber, indicating that knockdown of OTUD6B expression can significantly inhibit the invasion and migration of LUAD cells (Fig. 2J, K)."
38880876
OTUD6B affects Multiple Myeloma
| 3
OTUD6B activates Multiple Myeloma.
| 2
OTUD6B activates Multiple Myeloma. 2 / 2
| 2
reach
"Silencing OTUD6B or LIN28B inhibits multiple myeloma outgrowth in vivo and high OTUD6B expression evolves in patients that progress to symptomatic multiple myeloma and results in an adverse outcome of the disease."
36059274
reach
"One study found that OTUD6B drives the G1/S transition and promotes the proliferation of multiple myeloma cells by suppressing microRNA biogenesis via LIN28B stabilization [ 11 ]."
37634410
OTUD6B inhibits Multiple Myeloma.
| 1
OTUD6B inhibits Multiple Myeloma. 1 / 1
| 1
reach
"Inactivation of OTUD6B almost completely eliminates the growth of multiple myeloma (MM) in vivo through cell cycle arrest at the G1/S checkpoint, which is consistent with the associated loss of MYC expression [14]."
38880876
OTUD6B affects LUAD
| 3
OTUD6B activates LUAD. 3 / 3
| 3
reach
"OTUD6B knockdown suppressed LUAD tumor growth in a mouse model."
38880876
reach
"Overexpressing OTUD6B promotes LUAD progression."
38880876
reach
"These findings also provide strong evidence that the deubiquitinated protein OTUD6B promotes the malignant progression of LUAD by increasing the stability of the RIPK1 protein."
38880876
OTUD6B affects Interferon
| 3
OTUD6B inhibits Interferon.
| 2
OTUD6B inhibits Interferon. 2 / 2
| 2
reach
"Over-expression of Otud6b in zebrafish attenuated induction of viral and chemical IFN signaling, whereas loss of otud6b strongly promoted the antiviral response."
35923854
reach
"For instance, zebrafish ubiquitin-specific protease (USP) 5 positively regulates the type I IFN response, while sea perch USP5, orange-spotted grouper USP14, salmon A20, and zebrafish ovarian tumor do[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
38670412
OTUD6B activates Interferon.
| 1
OTUD6B activates Interferon. 1 / 1
| 1
reach
"Thus, unlike the previous report that zebrafish OTUD6B negatively regulates the antiviral response by suppressing K63-linked ubiquitination of IRF3 and IRF7, we demonstrate that human OTUD6B actually enhances type I IFN response and has the potential for antiviral therapy."
37650650
reach
"Biallelic mutations in the OTUD6B (Ovarian tumor domain-containing 6B) gene were recently described to cause an intellectual disability syndrome characterized by seizures and dysmorphic features in six families worldwide (Santiago-Sim et al., 2017; Online Mendelian Inheritance in Men, OMIM, #617452)."
30364145
reach
"Biallelic mutations in the ovarian tumor domain-containing 6B (OTUD6B) gene, coding for a deubiquitinating enzyme, were recently described to cause an intellectual disability syndrome characterized by seizures and dysmorphic features in six families worldwide."
30364145
Mutated OTUD6B activates Intellectual Disability. 1 / 1
| 1
reach
"In 2017, Autosomal recessive mutations of OTUD6B were first described to cause intellectual disability associated with seizure, dysmorphic features, and congenital malformations, including distal limb abnormalities."
| PMC
OTUD6B affects IRF7
| 1 1 1
OTUD6B binds IRF7.
| 1 1
OTUD6B binds IRF3 and IRF7. 1 / 1
| 1
sparser
"Further assays indicate that otud6b interacts with irf3 and irf7 and diminishes traf6-mediated K63-linked polyubiquitination of irf3 and irf7."
34183367
OTUD6B binds IRF7 and K63. 1 / 1
| 1
reach
"Further assays indicate that otud6b interacts with irf3 and irf7 and diminishes traf6 mediated K63 linked polyubiquitination of irf3 and irf7."
34183367
OTUD6B ubiquitinates IRF7.
| 1
OTUD6B ubiquitinates IRF7. 1 / 1
| 1
trips
"Zebrafish otud6b Negatively Regulates Antiviral Responses by Suppressing K63-Linked Ubiquitination of irf3 and irf7."
34183367
OTUD6B affects Hypoxia
| 3
OTUD6B activates Hypoxia. 3 / 3
| 3
reach
"Thus, Otud6b can modulate acute and chronic hypoxia responses."
38878112
reach
"Otud6b deficiency inhibits PAH development in hypoxia mice models."
38878112
reach
"According to the results of previous proteomic studies in our laboratory, the expression of Otud6b protein in the lung tissue of hypoxia induced PAH mice was significantly increased in the hypoxia group compared with the normal group."
38878112
OTUD6B affects HIF1
| 3
OTUD6B inhibits HIF1.
| 2
OTUD6B bound to VHL inhibits HIF1. 1 / 1
| 1
reach
"Otud6b can directly bind pVHL, reduce pVHL ubiquitination and proteasome degradation, and reduce HIF-1α accumulation in HCC cells under hypoxia conditions."
38878112
OTUD6B inhibits HIF1. 1 / 1
| 1
reach
"While in Hepatocellular carcinoma (HCC), OTUD6B decreases HIF-1α accumulation in HCC cells under hypoxia via directly interacting with pVHL to reduce its ubiquitination and proteasomal degradation, thereby inhibiting HCC cell metastasis [53]."
37752518
OTUD6B increases the amount of HIF1.
| 1
OTUD6B increases the amount of HIF1. 1 / 1
| 1
reach
"Our results also suggest that Otud6b can mediate HIF-1α protein expression."
38878112
OTUD6B affects GST
| 3
OTUD6B binds GST. 3 / 3
| 3
sparser
"Bacterial‐expressed GST and GST‐OTUD6B protein bound to glutathione‐sepharose 4B beads (from GE) was incubated with pVHL expressed in HEK293T cells for overnight at 4 °C. Then the beads were washed with PBS four times, followed by western blotting."
32328410
sparser
"To this end, we purified GST‐OTUD6B from bacteria and confirmed direct binding thereof to LIN28B (Fig  xref )."
36059274
sparser
"Next, GST‐OTUD6B was inserted into a reaction with FLAG‐purified ubiquitylated LIN28B from 293T cells."
36059274
Hypoxia affects OTUD6B
| 3
Hypoxia increases the amount of OTUD6B.
| 2
Hypoxia increases the amount of OTUD6B. 2 / 2
| 2
reach
"The expression of Otud6b in lung tissues of C57BL/6 mice was increased by hypoxia."
38878112
reach
"Compared with Nor group, hypoxia treatment significantly increased the expression levels of Otud6b protein and mRNA, which was consistent with the proteomic results."
38878112
Hypoxia decreases the amount of OTUD6B.
| 1
Hypoxia decreases the amount of OTUD6B. 1 / 1
| 1
reach
"Compared with hypoxia group, hypoxia + Calpain-1 knockout group not only improved the pathological changes of PAH, but also significantly reduced the protein expression of Otud6b, suggesting that Calpain-1 plays an important role in the regulation of Otud6b.Calpain is a conservative family of calcium dependent cysteine proteases that are commonly expressed in all cells [16, 17]."
38878112
GST affects OTUD6B
| 3
OTUD6B binds GST. 3 / 3
| 3
sparser
"Bacterial‐expressed GST and GST‐OTUD6B protein bound to glutathione‐sepharose 4B beads (from GE) was incubated with pVHL expressed in HEK293T cells for overnight at 4 °C. Then the beads were washed with PBS four times, followed by western blotting."
32328410
sparser
"To this end, we purified GST‐OTUD6B from bacteria and confirmed direct binding thereof to LIN28B (Fig  xref )."
36059274
sparser
"Next, GST‐OTUD6B was inserted into a reaction with FLAG‐purified ubiquitylated LIN28B from 293T cells."
36059274
Retinoic acid affects OTUD6B
| 2
reach
"Importantly, all‐trans retinoic acid (ATRA) was found to promote the OTUD6B translation, suppress the tumorigenesis and metastasis of ESCC, and enhance the response of established ESCC tumors to anti‐PD‐1 immunotherapy."
37038094
reach
"Importantly, all-trans retinoic acid (ATRA) is found to promote OTUD6B translation and thus suppress ESCC tumor growth and enhance the response of ESCC tumors to anti-PD-1 immunotherapies."
37038094
CircPTPN12 affects OTUD6B
| 2
CircPTPN12 binds OTUD6B. 2 / 2
| 2
reach
"RNA pull-down assays confirmed the association between PDLIM2, OTUD6B and circPTPN12 (Fig. 5C)."
38992675
reach
"Based on these findings, we propose the hypothesis that circPTPN12 facilitates the deubiquitination of PDLIM2 by binding to OTUD6B."
38992675
Cbc affects VHL
| 2
OTUD6B binds cbc and VHL. 2 / 2
| 2
sparser
"We used gel filtration chromatography assay to analyze the CBC VHL complex binding of OTUD6B. As shown in Figure xref and Figure S5F (Supporting Information), OTUD6B was detected in the same fractions with pVHL, elongin B, and elongin C, indicating that OTUD6B might be a component of CBC VHL complex."
32328410
sparser
"In this proposed model, OTUD6B is a direct transcriptional target of HIF‐1α, and HIF‐1α is a direct ubiquitylation and degradation target of OTUD6B‐CBC VHL complex."
32328410
PTK2 affects OTUD6B
1 | 1
OTUD6B binds PTK2. 1 / 2
1 | 1
sparser
"It is possible that some of the OTUD6B-related features are partly a result of defective interaction between the OTUD6B and PTK2 genes."
| PMC
OTUD6B affects viral process
| 2
OTUD6B inhibits viral process.
| 1
reach
"Collectively, these findings suggested that OTUD6B can inhibit viral infection."
37650650
OTUD6B activates viral process.
| 1
reach
"OTUD6B promoted type I IFN production in response to viral infection."
37650650
OTUD6B affects spindle assembly
| 2
reach
"We next sought to investigate whether the requirement for OTUD6B to limit multipolar spindle formation was linked to centrosome clustering, rather than to the maintenance of centrosome number or to centriole stability."
39789388
reach
"As in our previous experiments, OTUD6B depletion induced multipolar spindle formation, and this could be partially rescued by induction of KIFC1 (Fig. 3J)."
39789388
OTUD6B affects pathway
| 2
OTUD6B inhibits pathway.
| 1
OTUD6B inhibits pathway. 1 / 1
| 1
sparser
"Mechanistically, OTUD6B-AS1 inactivates the Wnt/β-catenin pathway and suppresses the expression of epithelial-to-mesenchymal transition-related proteins, including E-cadherin, N-cadherin and Snail in RCC cells [ xref ]."
33593347
OTUD6B activates pathway.
| 1
OTUD6B activates pathway. 1 / 1
| 1
sparser
"Interestingly, the RNA‐seq data suggested that depletion of OTUD6B remarkably activated HIF pathway in HCC cells (Figure S2C,D, Supporting Information)."
32328410
OTUD6B affects immune response
| 2
OTUD6B activates immune response. 2 / 2
| 2
reach
"OTUD6B promoted the type I IFN antiviral immune response in vivo ."
37650650
reach
"Furthermore, we found that human OTUD6B enhances type I IFN antiviral immune response in mice upon viral infection."
37650650
OTUD6B affects circPTPN12
| 2
CircPTPN12 binds OTUD6B. 2 / 2
| 2
reach
"RNA pull-down assays confirmed the association between PDLIM2, OTUD6B and circPTPN12 (Fig. 5C)."
38992675
reach
"Based on these findings, we propose the hypothesis that circPTPN12 facilitates the deubiquitination of PDLIM2 by binding to OTUD6B."
38992675
reach
"From a cell biological point of view, the OTUD6B‐LIN28B nexus links proteolytic ubiquitylation to mRNA biogenesis and eventually directs MYC activity to the G1/S cell cycle transition, a previously unappreciated crosstalk (Hildebrandt et al, 2017)."
36059274
reach
"Identification of OTUD6B as a dependency in MM that promotes the G1/S cell cycle transition."
36059274
OTUD6B affects autophagy
| 2
OTUD6B inhibits autophagy.
| 1
OTUD6B inhibits autophagy. 1 / 1
| 1
reach
"In addition, in triple-negative breast cancer, OTUD6B can activate autophagy and DDR inhibition through the OTUD6BAS1/miR-26a-5p/MTDH axis, thereby mediating genomic instability and promoting the development of PTX drug resistance [18]."
38880876
OTUD6B activates autophagy.
| 1
OTUD6B activates autophagy. 1 / 1
| 1
reach
"9 Moreover, lncRNA OTUD6B‐AS1 promotes paclitaxel resistance in TNBC by regulation of miR‐26a‐5p/MTDH pathway‐mediated autophagy."
37096846
reach
"Furthermore, NSCLC exposure to Torin-1 (an mTOR inhibitor, which target the mTOR catalytic site) abolished OTUD6B depletion enhanced AHA incorporation in these cells (XREF_FIG)."
27864334
reach
"Additionally, OTUD6B depletion increased AHA incorporation in H1734 and H1437 cells, and in transformed or primary cells other than NSCLC, specifically the mesothelioma cell line ME16, HaCaT immortalized human keratinocytes, and primary lung fibroblasts WI38 (XREF_FIG)."
27864334
OTUD6B affects VHL, and cbc
| 2
OTUD6B binds cbc and VHL. 2 / 2
| 2
sparser
"We used gel filtration chromatography assay to analyze the CBC VHL complex binding of OTUD6B. As shown in Figure xref and Figure S5F (Supporting Information), OTUD6B was detected in the same fractions with pVHL, elongin B, and elongin C, indicating that OTUD6B might be a component of CBC VHL complex."
32328410
sparser
"In this proposed model, OTUD6B is a direct transcriptional target of HIF‐1α, and HIF‐1α is a direct ubiquitylation and degradation target of OTUD6B‐CBC VHL complex."
32328410
OTUD6B affects Ubiquitin
| 1 1
OTUD6B inhibits Ubiquitin.
| 1
OTUD6B inhibits Ubiquitin. 1 / 1
| 1
reach
"24 Here we show that OTUD6B reduces Ub(n)‐ubiquitinylated substrates, especially polyubiquitin chains, demonstrating that it is a bona fide DUB."
37038094
OTUD6B binds Ubiquitin.
| 1
sparser
"However, in cells OTUD6B binds ubiquitin active site-directed probes (Catic et al, xref ; Pinto-Fernandez et al, xref ) and exhibits enzymatic activity towards Ub-Met-β-gal that is reliant upon the catalytic cysteine (Xu et al, xref ), confirming it as an active DUB."
39789388
OTUD6B inhibits Triple Negative Breast Neoplasms. 2 / 2
| 2
reach
"In breast cancer, over-expression of OTUD6B‐AS1 has been found to promote autophagy and thus genomic instability via the lncRNA OTUD6B-AS1/miR-26a-5p/MTDH signalling pathway, this lncRNA promotes the progression of triple-negative breast cancer 19."
37781080
reach
"In addition, in triple-negative breast cancer, OTUD6B can activate autophagy and DDR inhibition through the OTUD6BAS1/miR-26a-5p/MTDH axis, thereby mediating genomic instability and promoting the development of PTX drug resistance [18]."
38880876
OTUD6B affects Syndrome
| 2
OTUD6B activates Syndrome. 2 / 2
| 2
reach
"Biallelic mutations in the ovarian tumor domain-containing 6B (OTUD6B) gene, coding for a deubiquitinating enzyme, were recently described to cause an intellectual disability syndrome characterized by seizures and dysmorphic features in six families worldwide."
30364145
reach
"Biallelic mutations in the OTUD6B (Ovarian tumor domain-containing 6B) gene were recently described to cause an intellectual disability syndrome characterized by seizures and dysmorphic features in six families worldwide (Santiago-Sim et al., 2017; Online Mendelian Inheritance in Men, OMIM, #617452)."
30364145
OTUD6B affects PSD4
| 2
OTUD6B inhibits PSD4. 2 / 2
| 2
reach
"Thus, these results demonstrated that OTUD6B inhibited TIC properties of ESCC cells by decreasing SNAIL stability.2.5 Reduced OTUD6B Predicts a Poor Prognosis in Esophageal Squamous Cell Carcinoma Patients."
37038094
reach
"Taken together, these results showed that ATRA upregulated the protein level of OTUD6B in ESCC cells and inhibited their TIC properties.Interestingly, we noted that the effects of ATRA in suppressing TIC properties were diminished in OTUD6B‐knockdown cells (Figure 6B–F)."
37038094
OTUD6B affects PAH mice
| 2
OTUD6B activates PAH mice. 2 / 2
| 2
reach
"We detected Otud6b expression levels in a hypoxia induced PAH mice model."
38878112
reach
"Therefore, our results indicate increased Otud6b expression in hypoxia induced PAH mice models."
38878112
OTUD6B inhibits Neoplasm Metastasis. 2 / 2
| 2
reach
"OTUD6B knockdown enhanced apoptosis and inhibited metastasis in LUAD cells."
38880876
reach
"Consistent with this mechanism, over-expression of pVHL could antagonize OTUD6B depletion-induced effects in HCC cell migration and metastasis."
32323143
OTUD6B affects HYCC1
| 2
OTUD6B bound to VHL inhibits HYCC1. 1 / 1
| 1
reach
"Otud6b can directly bind pVHL, reduce pVHL ubiquitination and proteasome degradation, and reduce HIF-1α accumulation in HCC cells under hypoxia conditions."
38878112
OTUD6B inhibits HYCC1. 1 / 1
| 1
reach
"While in Hepatocellular carcinoma (HCC), OTUD6B decreases HIF-1α accumulation in HCC cells under hypoxia via directly interacting with pVHL to reduce its ubiquitination and proteasomal degradation, thereby inhibiting HCC cell metastasis [53]."
37752518
OTUD6B affects HIF
| 1 1
OTUD6B increases the amount of HIF.
| 1
OTUD6B increases the amount of HIF. 1 / 1
| 1
reach
"Although this study did not specifically examine whether the activation of HIF itself through hypoxia is regulated by Otud6b, we found that activation of Otud6b expression with rOtud6b does increase HIF expression, which further regulates the transcription of cytokines and important proteins (such as VEGF, ET-1, etc.), which contribute to the development of PAH.We further discussed the regulatory relationship between Otud6b and HIF-1α."
38878112
OTUD6B binds HIF.
| 1
OTUD6B binds HIF. 1 / 1
| 1
sparser
"In the cytoplasm, Otud6b interacts with HIF, which mediates the cell’s transcriptional response to hypoxia."
38878112
OTUD6B affects Fig. 5F-G
| 2
OTUD6B ubiquitinates Fig. 5F-G.
| 1
OTUD6B leads to the ubiquitination of Fig. 5F-G. 1 / 1
| 1
reach
"Immunoprecipitation (IP) results indicated that the knockdown of OTUD6B effectively enhanced the ubiquitylation of PDLIM2, while overexpression of OTUD6B decreased the ubiquitylation of PDLIM2 (Fig. 5F-G)."
38992675
OTUD6B deubiquitinates Fig. 5F-G.
| 1
OTUD6B leads to the deubiquitination of Fig. 5F-G. 1 / 1
| 1
reach
"Immunoprecipitation (IP) results indicated that the knockdown of OTUD6B effectively enhanced the ubiquitylation of PDLIM2, while overexpression of OTUD6B decreased the ubiquitylation of PDLIM2 (Fig. 5F-G)."
38992675
OTUD6B inhibits Carcinoma, Renal Cell. 2 / 2
| 2
reach
"It has reported that OTUD6B downregulated in kidney clear cell renal cell carcinoma, kidney renal papillary cell carcinoma compared to healthy sample (Zhao G. et al., 2022), (Guo et al., 2022), and its expression level correlated with survival in VHL missense mutation patients."
40034749
reach
"The deubiquitinase OTUD6B inhibits cell migration in clear cell renal cell carcinoma and hepatocellular carcinoma by stabilizing mutated pVHL [16]."
38880876
OTUD6B activates Adenocarcinoma of Lung. 2 / 2
| 2
reach
"The deubiquitinating protein OTUD6B promotes lung adenocarcinoma progression by stabilizing RIPK1."
38880876
reach
"In lung adenocarcinoma, the deubiquitinated protein OTUD6B promotes tumor progression by stabilizing RIPK1 [46]."
40170095
IRF7 affects OTUD6B
| 1 1
OTUD6B binds IRF3 and IRF7. 1 / 1
| 1
sparser
"Further assays indicate that otud6b interacts with irf3 and irf7 and diminishes traf6-mediated K63-linked polyubiquitination of irf3 and irf7."
34183367
OTUD6B binds IRF7 and K63. 1 / 1
| 1
reach
"Further assays indicate that otud6b interacts with irf3 and irf7 and diminishes traf6 mediated K63 linked polyubiquitination of irf3 and irf7."
34183367
Calpain-1 inhibitor affects OTUD6B
| 2
Calpain-1 inhibitor inhibits OTUD6B.
| 1
Calpain-1 inhibitor inhibits OTUD6B. 1 / 1
| 1
reach
"6I-J and 7D-E) showed that the Calpain-1 inhibitor MDL could reduce the mRNA and protein expression levels of Otud6b in HPAECs and HPASMCs compared with the Hypoxia group."
38878112
Calpain-1 inhibitor decreases the amount of OTUD6B.
| 1
Calpain-1 inhibitor decreases the amount of OTUD6B. 1 / 1
| 1
reach
"Calpain-1 inhibitor reduce the expression of Otud6b in HPAECs and HPASMCs of hypoxia induced vitro model."
38878112
PVHL affects OTUD6B
| 1
OTUD6B binds pVHL. 1 / 1
| 1
isi
"OTUD6B directly interacts with pVHL, decreases its ubiquitylation and proteasomal degradation to reduce HIF-1alpha accumulation in HCC cells under hypoxia."
32328410
Oxide affects OTUD6B
| 1
Oxide activates OTUD6B. 1 / 1
| 1
reach
"To explore the role of OTUD6B in regulating ESCC progression, we induced ESCC tumors by 4‐nitroquinoline 1‐oxide (4NQO) in Otud6b WT and cKO backgrounds 14 (Figure 3M)."
37038094
Omacetaxine mepesuccinate activates OTUD6B. 1 / 1
| 1
reach
"siRNAs to OTUD6B were unable to modify AHA incorporation when cells were treated with cycloheximide or homoharringtonine (XREF_FIG, left)."
27864334
Mtf1 affects OTUD6B
| 1
Delta-actitoxin-Avd1a binds OTUD6B and mtf1. 1 / 1
| 1
sparser
"As shown in xref , the luciferase activity driven by the WT promoter sequence was markedly reduced by MTF1 knockdown, indicating that the WT sites are required for binding of MTF1 to the lncRNA OTUD6B-AS1 promoter."
32952848
MdlB affects OTUD6B
| 1
MdlB decreases the amount of OTUD6B. 1 / 1
| 1
reach
"Calpain-1 KO mice and Calpain-1 inhibitor MDL inhibited Calpain-1 protein expression, decreased Otud6b protein expression, and further improved PAH."
38878112
Bortezomib affects OTUD6B
| 1
Bortezomib inhibits OTUD6B. 1 / 1
| 1
reach
"By contrast, we speculate that OTUD6B inhibition outweighs the net effect of bortezomib treatment on LIN28B under clinically achievable bortezomib levels and that this effect adds to the general proteotoxic stress induced by bortezomib in order to explain the observed synergy of OTUD6B inhibition and proteasomal inhibition.Unbiased screening identified OTUD6B as a vulnerability in MM."
36059274
Ubiquitin affects OTUD6B
| 1
sparser
"However, in cells OTUD6B binds ubiquitin active site-directed probes (Catic et al, xref ; Pinto-Fernandez et al, xref ) and exhibits enzymatic activity towards Ub-Met-β-gal that is reliant upon the catalytic cysteine (Xu et al, xref ), confirming it as an active DUB."
39789388
TNFSF13B affects OTUD6B
| 1
TNFSF13B increases the amount of OTUD6B. 1 / 1
| 1
reach
"BAFF, a B cell activating factor of the TNF family, could also induce Otud-6b expression on mouse B cells after 4 hours stimulation XREF_BIBR."
21267069
SNAI1 affects OTUD6B
| 1
OTUD6B binds SNAI1. 1 / 1
| 1
reach
"The results showed that OTUD6B could bind with SNAIL but not β‐catenin or IκBα (Figure 4C)."
37038094
ROtud6b affects OTUD6B
| 1
ROtud6b activates OTUD6B. 1 / 1
| 1
reach
"ROtud6b activates Otud6b, induces HIF-1alpha activation, increases the production of ET-1 and VEGF, and further aggravates endothelial injury."
38878112
RAR affects OTUD6B
| 1
RAR decreases the amount of OTUD6B. 1 / 1
| 1
reach
"We found that knockdown of RARα significantly increased the protein level of OTUD6B in ESCC cells, while ectopic expression of RARα decreased it (Figure 6K,L)."
37038094
OTUD7A affects OTUD6B
| 1
OTUD6B binds OTUD7A. 1 / 1
| 1
reach
"We found that OTUD3, OTUD4, OTUD6B, and OTUD7A bound to EWS–FLI1 in cells (Figure 3B)."
34060252
OTUD6B affects β‐TrCP protein
| 1
OTUD6B decreases the amount of β‐TrCP protein. 1 / 1
| 1
reach
"By increasing β‐TrCP protein level and activating an OTUD6B‐β‐TrCP‐SNAIL axis, OTUD6B suppresses the TIC properties of ESCC cells."
37038094
OTUD6B inhibits viral RNA genome replication. 1 / 1
| 1
reach
"Alternatively, the expression of endogenous human OTUD6B was downregulated by transfection of specific small-interfering RNA (siRNA) in 293T cells (Fig. 1C), and knockdown of OTUD6B mediated by siRNA consistently promoted viral replication (Fig. 1D through G)."
37650650
OTUD6B affects ubiquitination pVHL
| 1
OTUD6B inhibits ubiquitination pVHL. 1 / 1
| 1
eidos
"More interestingly , OTU deubiquitinase 6B ( OTUD6B ) as the first reported deubiquitination enzyme is capable of inhibiting pVHL ubiquitination , and the deubiquitination regulation of OTUD6B on pVHL did not depend on its enzyme activity , but via interaction with pVHL to enhance the stability of CBCVHL ubiquitin ligase complex , and reduce the ubiquitination degradation of pVHL by Trp-Asp repeat and suppressors of cytokine signaling box-containing protein 1 ( WSB1 ) and E2-EPF ubiquitin carrier protein ( UCP ) ."
33109235
OTUD6B affects ubiquitin E3
| 1
OTUD6B inhibits ubiquitin E3. 1 / 1
| 1
reach
"Alternatively, OTUD6B might antagonise another ubiquitin E3 ligase."
39789388
OTUD6B affects tube formation
| 1
OTUD6B activates tube formation. 1 / 1
| 1
reach
"Figure 10J demonstrated that OTUD6B−AS1 enhanced the tube formation capacity of HUVEC."
37543427
OTUD6B affects translation
| 1
OTUD6B activates translation. 1 / 1
| 1
reach
"OTUD6B depletion caused an increased rate of cap dependent translation."
27864334
OTUD6B affects traf6-mediated K63-linked polyubiquitination irf3 irf7
| 1
OTUD6B inhibits traf6-mediated K63-linked polyubiquitination irf3 irf7. 1 / 1
| 1
eidos
"Further assays indicate that otud6b interacts with irf3 and irf7 and diminishes traf6-mediated K63-linked polyubiquitination of irf3 and irf7 ."
34183367
OTUD6B affects tbk1 bind irf3 irf7 resulting irf3 irf7 phosphorylation
| 1
OTUD6B inhibits tbk1 bind irf3 irf7 resulting irf3 irf7 phosphorylation. 1 / 1
| 1
eidos
"Moreover , otud6b also attenuates tbk1 to bind to irf3 and irf7 , resulting in the impairment of irf3 and irf7 phosphorylation ."
34183367
OTUD6B activates signal transduction. 1 / 1
| 1
reach
"Otud6b induces pulmonary arterial hypertension by mediating the Calpain-1/HIF-1alpha signaling pathway."
38878112
OTUD6B bound to VHL inhibits proteasome complex disassembly. 1 / 1
| 1
reach
"Otud6b can directly bind pVHL, reduce pVHL ubiquitination and proteasome degradation, and reduce HIF-1α accumulation in HCC cells under hypoxia conditions."
38878112
OTUD6B affects phosphorylation IRFs molecules
| 1
OTUD6B inhibits phosphorylation IRFs molecules. 1 / 1
| 1
eidos
"Besides , OTUD6B can also inhibit the binding of TBK1 to IRF3 and IRF7 and damage the phosphorylation of IRFs molecules ."
34966378
OTUD6B affects pVHL
| 1
OTUD6B binds pVHL. 1 / 1
| 1
isi
"OTUD6B directly interacts with pVHL, decreases its ubiquitylation and proteasomal degradation to reduce HIF-1alpha accumulation in HCC cells under hypoxia."
32328410
OTUD6B affects mtf1
| 1
Delta-actitoxin-Avd1a binds OTUD6B and mtf1. 1 / 1
| 1
sparser
"As shown in xref , the luciferase activity driven by the WT promoter sequence was markedly reduced by MTF1 knockdown, indicating that the WT sites are required for binding of MTF1 to the lncRNA OTUD6B-AS1 promoter."
32952848
reach
"This is consistent with a model where OTUD6B modulates KIFC1 accumulation in early mitosis, when supernumerary centrosome clustering is initially required for spindle formation."
39789388
OTUD6B affects miRNA processing
| 1
reach
"One study found that OTUD6B drives the G1/S transition and promotes the proliferation of multiple myeloma cells by suppressing microRNA biogenesis via LIN28B stabilization [ 11 ]."
37634410
OTUD6B affects mdlB
| 1
OTUD6B inhibits mdlB. 1 / 1
| 1
reach
"Activation of Otud6b protein expression with rOtud6b reversed the regulation of Calpain-1 KO and MDL and exacerbated the progression of PAH.Interestingly, our experimental results show that HIF-1α and Calpain-1/Otud6b regulate each other through positive feedback."
38878112
reach
"We found that activation of Otud6b expression with rOtud6b increased endothelial cell inflammation and apoptosis, smooth muscle cells inflammation and proliferation."
38878112
OTUD6B affects growth
| 1
OTUD6B inhibits growth. 1 / 1
| 1
sparser
"When TgMMTV-neu mice (n=5/group) were vaccinated with the individual antigens, vaccination with Pdhx inhibited tumor growth by 62.1%, Otud6B inhibited tumor growth by 23.5%, and Stk39 inhibited tumor growth by 50.3% as compared to empty vector vaccinated control at 27 weeks (p<0.001 for each individual antigen as compared to empty vector)."
| PMC
OTUD6B affects dissociation Cullin 2VHL complex pVHL known upstream E3 ligases
| 1
OTUD6B activates dissociation Cullin 2VHL complex pVHL known upstream E3 ligases. 1 / 1
| 1
eidos
"On the other hand , depletion of OTUD6B results in the dissociation of Cullin 2VHL complex and the degradation of pVHL presumably by known upstream E3 ligases such as WSB1 ( Kim et al ., 2015 ) or E2-EPF-UCP ( Jung et al ., 2006 ) ."
32323143
OTUD6B affects cells migration
| 1
OTUD6B inhibits cells migration. 1 / 1
| 1
eidos
"Using siRNA-based targeted screening , the authors found that OTUD6B , but not other OTU family members , could significantly suppress HCC cells migration and metastasis ."
32323143
OTUD6B affects cell renal cell carcinoma
| 1
OTUD6B inhibits cell renal cell carcinoma. 1 / 1
| 1
eidos
"OTUD6B was found to inhibit clear cell renal cell carcinoma by regulating the Wnt / beta-catenin pathway and suppressing EMT-related protein expression ( 31 ) ."
33000250
OTUD6B affects cell cycle
| 1
OTUD6B activates cell cycle. 1 / 1
| 1
reach
"However, the rapid down-regulation of Otud-6b is probably required to maintain a normal cell cycle as enforced Otud-6b expression can cause cell cycle arrest in Ba/F3 cells."
21267069
OTUD6B affects binding TBK1 IRF3 IRF7
| 1
OTUD6B inhibits binding TBK1 IRF3 IRF7. 1 / 1
| 1
eidos
"Besides , OTUD6B can also inhibit the binding of TBK1 to IRF3 and IRF7 and damage the phosphorylation of IRFs molecules ."
34966378
OTUD6B affects beta-TrCP Protein Stability
| 1
OTUD6B activates beta-TrCP Protein Stability. 1 / 1
| 1
reach
"2.1 OTUD6B Enhances beta-TrCP Protein Stability."
37038094
OTUD6B affects angiogenesis
| 1
OTUD6B inhibits angiogenesis. 1 / 1
| 1
reach
"Wang et al. [11] showed that Otud6b reduces angiogenesis of atherosclerotic plaques, enhances plaque stability and delays the progression of atherosclerosis by regulating the proliferation, migration and lumen formation of endothelial cells."
38878112
OTUD6B affects Wnt
| 1
OTUD6B activates Wnt. 1 / 1
| 1
reach
"Further, lncRNA OTUD6B can inhibit ccRCC cell proliferation by suppressing the Wnt and beta-catenin pathway and the expressions of epithelial-to-mesenchymal transition related proteins."
33692953
OTUD6B affects VEGF
| 1
OTUD6B activates VEGF. 1 / 1
| 1
reach
"Otud6b increases HPAECs production of HIF-1alpha, ET-1 and VEGF."
38878112
OTUD6B affects TRAF6-induced K63-linked polyubiquitination IRF3 IRF7
| 1
OTUD6B inhibits TRAF6-induced K63-linked polyubiquitination IRF3 IRF7. 1 / 1
| 1
eidos
"OTUD6B , another member of the OTUD family , was found to inhibit TRAF6-induced K63-linked polyubiquitination of IRF3 and IRF7 in zebrafish , depending on the role of the OTU domain ."
34966378
OTUD6B affects TRAF6
| 1
OTUD6B bound to IRF3 inhibits TRAF6. 1 / 1
| 1
reach
"Further assays indicate that otud6b interacts with irf3 and irf7 and diminishes traf6 mediated K63 linked polyubiquitination of irf3 and irf7."
34183367
OTUD6B affects TBK1
| 1
OTUD6B inhibits TBK1. 1 / 1
| 1
reach
"Moreover, otud6b also attenuates tbk1 to bind to irf3 and irf7, resulting in the impairment of irf3 and irf7 phosphorylation."
34183367
OTUD6B affects Survival Rate
| 1
eidos
"Disruption of otud6b in zebrafish increases the survival rate upon spring viremia of carp virus and grass carp reovirus exposure ."
34183367
OTUD6B affects STAT3
| 1
OTUD6B leads to the phosphorylation of STAT3. 1 / 1
| 1
reach
"OTUD6B promotes cholangiocarcinoma growth by regulating STAT3 phosphorylation through deubiquitination of PTK2."
39192576
sparser
"More interestingly, another major finding was that the molecular mechanism involved lncRNA OTUD6B-AS1 inhibition of IDH2 expression through stabilization of miR-6734-5p ( xref )."
32952848
reach
"Wang et al. [11] showed that Otud6b reduces angiogenesis of atherosclerotic plaques, enhances plaque stability and delays the progression of atherosclerosis by regulating the proliferation, migration and lumen formation of endothelial cells."
38878112
OTUD6B affects PCSK9
| 1
OTUD6B activates PCSK9. 1 / 1
| 1
reach
"It is also obvious that OTUD6B silencing inhibited the proliferation, migration, and invasion of A549 and Pc9 cells ( Figures 10C–E )."
36052059
OTUD6B affects OTUD7A
| 1
OTUD6B binds OTUD7A. 1 / 1
| 1
reach
"We found that OTUD3, OTUD4, OTUD6B, and OTUD7A bound to EWS–FLI1 in cells (Figure 3B)."
34060252
OTUD6B affects OTUD6B
| 1
OTUD6B inhibits OTUD6B. 1 / 1
| 1
reach
"Our data showed that OTUD6B overexpression suppressed infection by all these viruses, indicating the broad-spectrum antiviral effects of OTUD6B (Fig. 2C)."
37650650
OTUD6B affects OTUD4
| 1
OTUD4 binds OTUD6B. 1 / 1
| 1
reach
"We found that OTUD3, OTUD4, OTUD6B, and OTUD7A bound to EWS–FLI1 in cells (Figure 3B)."
34060252
OTUD6B affects OTUD3
| 1
OTUD3 binds OTUD6B. 1 / 1
| 1
reach
"We found that OTUD3, OTUD4, OTUD6B, and OTUD7A bound to EWS–FLI1 in cells (Figure 3B)."
34060252
OTUD6B affects LSCC
| 1
OTUD6B activates LSCC. 1 / 1
| 1
reach
"In the current study, using AMC–HN–8 and TU177 cells as representative LSCC models, we confirmed that OTUD6B overexpression enhanced the proliferation of LSCC in vitro and in vivo ."
37634410
OTUD6B affects K63
| 1
OTUD6B binds IRF7 and K63. 1 / 1
| 1
reach
"Further assays indicate that otud6b interacts with irf3 and irf7 and diminishes traf6 mediated K63 linked polyubiquitination of irf3 and irf7."
34183367
OTUD6B affects K11-
| 1
OTUD6B binds K11-. 1 / 1
| 1
reach
"The OTUD6B interacts with IRF3 and cleaves K11- and K33-linked ubiquitin chains of IRF3."
37650650
OTUD6B affects Infections
| 1
OTUD6B inhibits Infections. 1 / 1
| 1
reach
"Our data showed that OTUD6B overexpression suppressed infection by all these viruses, indicating the broad-spectrum antiviral effects of OTUD6B (Fig. 2C)."
37650650
OTUD6B affects IFNB1
| 1
OTUD6B activates IFNB1. 1 / 1
| 1
reach
"Our data showed that OTUD6B knockdown strongly attenuated IFN-β reporter luciferase activity (Fig. 3A) and downstream IFN-stimulatory response element activity (Fig. 3B)."
37650650
OTUD6B affects IFN-1 activation K63-linked polyubiquitination irf3 irf7
| 1
OTUD6B inhibits IFN-1 activation K63-linked polyubiquitination irf3 irf7. 1 / 1
| 1
eidos
"In addition , the OTU domain is required for otud6b to repress IFN-1 activation and K63-linked polyubiquitination of irf3 and irf7 ."
34183367
OTUD6B affects IDDFSDA
| 1
OTUD6B activates IDDFSDA. 1 / 1
| 1
reach
"Recently, biallelic variants in OTUD6B have been reported to cause IDDFSDA, characterized by a wide clinical spectrum (Santiago-Sim et al., 2017)."
35430327
OTUD6B affects ID1
| 1
OTUD6B binds ID1. 1 / 1
| 1
sparser
"Because OTUD6B is associated with autosomal recessive ID, with characteristic phenotypes that matched our patient’s manifestations, we believed that there could be another OTUD6B mutation in compound with the 8q21.3 microdeletion that is responsible for the patient’s phenotypes."
| PMC
OTUD6B affects Hypertension
| 1
OTUD6B activates Hypertension. 1 / 1
| 1
reach
"Otud6b induces pulmonary arterial hypertension by mediating the Calpain-1/HIF-1alpha signaling pathway."
38878112
OTUD6B affects Hand
| 1
OTUD6B inhibits Hand. 1 / 1
| 1
eidos
"On the other hand , depletion of OTUD6B results in the dissociation of Cullin 2VHL complex and the degradation of pVHL presumably by known upstream E3 ligases such as WSB1 ( Kim et al ., 2015 ) or E2-EPF-UCP ( Jung et al ., 2006 ) ."
32323143
OTUD6B affects HUVEC
| 1
OTUD6B activates HUVEC. 1 / 1
| 1
reach
"Figure 10J demonstrated that OTUD6B−AS1 enhanced the tube formation capacity of HUVEC."
37543427
OTUD6B affects First Spanish case
| 1
OTUD6B activates First Spanish case. 1 / 1
| 1
reach
"[First Spanish case of syndromic intellectual disability with dysmorphic facies, seizures, and distal limb anomalies caused by balletic mutations in the OTUD6B gene]."
31147255
OTUD6B affects FBN2
| 1
OTUD6B activates FBN2. 1 / 1
| 1
reach
"In CCA cells, OTUD6B knockdown reduced CCA cell proliferation and promoted apoptosis."
39192576
OTUD6B affects EV4A
| 1
OTUD6B leads to the ubiquitination of EV4A. 1 / 1
| 1
reach
"Indeed, siRNA‐mediated knockdown of OTUD6B substantially enhanced polyubiquitylation of LIN28B (Fig 2B), whereas forced expression of OTUD6B decreased LIN28B ubiquitylation (Figs 2C and EV4A)."
36059274
OTUD6B affects EDN1
| 1
OTUD6B activates EDN1. 1 / 1
| 1
reach
"Otud6b increases HPAECs production of HIF-1alpha, ET-1 and VEGF."
38878112
sparser
"In addition, the differential expression levels of lncRNAs included TSIX, NRIR, ncRNA00201, OTUD6B-AS, CTBP1-AS2, AGAP2-AS1, and HIFA-AS1, which can target mRNAs and might also involve pathogenesis and pathological changes in patients with SSc."
| PMC
OTUD6B affects DDR
| 1
OTUD6B inhibits DDR. 1 / 1
| 1
reach
"In addition, in triple-negative breast cancer, OTUD6B can activate autophagy and DDR inhibition through the OTUD6BAS1/miR-26a-5p/MTDH axis, thereby mediating genomic instability and promoting the development of PTX drug resistance [18]."
38880876
OTUD6B affects Cyclin
| 1
OTUD6B activates Cyclin. 1 / 1
| 1
reach
"Nevertheless, OTUD-6B probably could directly affect either the synthesis or the degradation process of cyclin D2 as overexpressing OTUD-6B in Hela cells could also cause cyclin D2 expression level down-regulation even without affecting cell cycle (XREF_SUPPLEMENTARY)."
21267069
OTUD6B affects Cullin 2VHL E3 ligase complex
| 1
OTUD6B activates Cullin 2VHL E3 ligase complex. 1 / 1
| 1
eidos
"OTUD6B enhances the formation of stable Cullin 2VHL E3 ligase complex , which protects pVHL from proteasomal degradation ."
32323143
OTUD6B inhibits Carcinoma, Hepatocellular. 1 / 1
| 1
reach
"The deubiquitinase OTUD6B inhibits cell migration in clear cell renal cell carcinoma and hepatocellular carcinoma by stabilizing mutated pVHL [16]."
38880876
OTUD6B affects Carcinoma
| 1
OTUD6B inhibits Carcinoma. 1 / 1
| 1
reach
"It has reported that OTUD6B downregulated in kidney clear cell renal cell carcinoma, kidney renal papillary cell carcinoma compared to healthy sample (Zhao G. et al., 2022), (Guo et al., 2022), and its expression level correlated with survival in VHL missense mutation patients."
40034749
OTUD6B affects Calpain-1 KO
| 1
OTUD6B inhibits Calpain-1 KO. 1 / 1
| 1
reach
"Activation of Otud6b protein expression with rOtud6b reversed the regulation of Calpain-1 KO and MDL and exacerbated the progression of PAH.Interestingly, our experimental results show that HIF-1α and Calpain-1/Otud6b regulate each other through positive feedback."
38878112
OTUD6B affects CTNNB1
| 1
OTUD6B activates CTNNB1. 1 / 1
| 1
reach
"Further, lncRNA OTUD6B can inhibit ccRCC cell proliferation by suppressing the Wnt and beta-catenin pathway and the expressions of epithelial-to-mesenchymal transition related proteins."
33692953
OTUD6B affects CTBP1
| 1
sparser
"In addition, the differential expression levels of lncRNAs included TSIX, NRIR, ncRNA00201, OTUD6B-AS, CTBP1-AS2, AGAP2-AS1, and HIFA-AS1, which can target mRNAs and might also involve pathogenesis and pathological changes in patients with SSc."
| PMC
OTUD6B affects CDH1
| 1
OTUD6B decreases the amount of CDH1. 1 / 1
| 1
reach
"The expression of E-cadherin was reduced by OTUD6B−AS1, while the expressions of HIF-1α, MMP1, SMAD5, Snail, Twist1, and VEGFA were increased (Figure 10K)."
37543427
OTUD6B affects CD3
| 1
OTUD6B inhibits CD3. 1 / 1
| 1
reach
"For mice vaccinated with Pdhx, Stk39, and Otud6B depletion of CD3 + T cells increased tumor growth (p < 0.0001 compared to empty vector control for all targets)."
31126858
OTUD6B affects CAPN1
| 1
OTUD6B activates CAPN1. 1 / 1
| 1
reach
"Otud6b induces pulmonary arterial hypertension by mediating the Calpain-1/HIF-1alpha signaling pathway."
38878112
OTUD6B affects BTRC
| 1
OTUD6B leads to the deubiquitination of BTRC. 1 / 1
| 1
reach
"Although OTUD6B regulates pVHL independently of its DUB activity (Liu et al, 2020), the catalytic cysteine of OTUD6B is required to limit ubiquitination of β-TrCP (Li et al, 2023) and LIN28B (Paulmann et al, 2022), as we found for KIFC1 (Fig. 6C)."
39789388
OTUD4 affects OTUD6B
| 1
OTUD4 binds OTUD6B. 1 / 1
| 1
reach
"We found that OTUD3, OTUD4, OTUD6B, and OTUD7A bound to EWS–FLI1 in cells (Figure 3B)."
34060252
OTUD3 affects OTUD6B
| 1
OTUD3 binds OTUD6B. 1 / 1
| 1
reach
"We found that OTUD3, OTUD4, OTUD6B, and OTUD7A bound to EWS–FLI1 in cells (Figure 3B)."
34060252
reach
"The ESCC metastasis was also inhibited by overexpressing OTUD6B but not OTUD6B , but increased by knockdown of OTUD6B (Figure 3H–K and Figure S3H–K, Supporting Information)."
37038094
MYC affects OTUD6B
| 1
OTUD6B binds MYC. 1 / 1
| 1
sparser
"We constructed overexpression plasmids Myc-UCHL-1, Myc-CPT1B, and Myc-OTUD6B. Then, these plasmids were co-transfected with Flag-Metrnl in HEK293T cell lines, respectively."
38745648
KIFC1 affects OTUD6B
| 1
KIFC1 binds OTUD6B. 1 / 1
| 1
sparser
"In common with these two substrates, KIFC1 interacts with the N-terminus of OTUD6B (Fig.  xref ) (Li et al, xref ; Paulmann et al, xref )."
39789388
K63 affects OTUD6B
| 1
OTUD6B binds IRF7 and K63. 1 / 1
| 1
reach
"Further assays indicate that otud6b interacts with irf3 and irf7 and diminishes traf6 mediated K63 linked polyubiquitination of irf3 and irf7."
34183367
K11- affects OTUD6B
| 1
OTUD6B binds K11-. 1 / 1
| 1
reach
"The OTUD6B interacts with IRF3 and cleaves K11- and K33-linked ubiquitin chains of IRF3."
37650650
reach
"Additionally, it was found that biallelic variants in human OTUD6B cause intellectual disability syndrome (27)."
37650650
IRF7 affects K63, and OTUD6B
| 1
OTUD6B binds IRF7 and K63. 1 / 1
| 1
reach
"Further assays indicate that otud6b interacts with irf3 and irf7 and diminishes traf6 mediated K63 linked polyubiquitination of irf3 and irf7."
34183367
IRF7 affects IRF3
| 1
OTUD6B binds IRF3 and IRF7. 1 / 1
| 1
sparser
"Further assays indicate that otud6b interacts with irf3 and irf7 and diminishes traf6-mediated K63-linked polyubiquitination of irf3 and irf7."
34183367
IL4 affects OTUD6B
| 1
IL4 activates OTUD6B. 1 / 1
| 1
reach
"Here we report that Otud-6b, a functional DUB of the OTU family, can be induced by IL-3, IL-4, IL-13 and granulocyte-macrophage colony stimulating factor (GM-CSF) stimulation in B lymphocytes."
21267069
IL3 affects OTUD6B
| 1
IL3 activates OTUD6B. 1 / 1
| 1
reach
"Here we report that Otud-6b, a functional DUB of the OTU family, can be induced by IL-3, IL-4, IL-13 and granulocyte-macrophage colony stimulating factor (GM-CSF) stimulation in B lymphocytes."
21267069
IL2 affects OTUD6B
| 1
IL2 increases the amount of OTUD6B. 1 / 1
| 1
reach
"On the other hand, IL-2 could not induce Otud-6b expression in Ba/F3 cells (XREF_SUPPLEMENTARY)."
21267069
IL13 affects OTUD6B
| 1
IL13 activates OTUD6B. 1 / 1
| 1
reach
"Here we report that Otud-6b, a functional DUB of the OTU family, can be induced by IL-3, IL-4, IL-13 and granulocyte-macrophage colony stimulating factor (GM-CSF) stimulation in B lymphocytes."
21267069
ID1 affects OTUD6B
| 1
OTUD6B binds ID1. 1 / 1
| 1
sparser
"Because OTUD6B is associated with autosomal recessive ID, with characteristic phenotypes that matched our patient’s manifestations, we believed that there could be another OTUD6B mutation in compound with the 8q21.3 microdeletion that is responsible for the patient’s phenotypes."
| PMC
HMBS affects OTUD6B
| 1
HMBS activates OTUD6B. 1 / 1
| 1
reach
"These results address the long‐standing questions in how far DUBs can serve as actionable therapeutic targets in cancer, particularly in patients with MM and how the UPS can contribute to the conversion of MGUS to MM.Targeting OTUD6B provides a strategy to activate let‐7 microRNAs via LIN28B destabilization to repress their targets, of which we show that MYC is the prominent determinant in MM."
36059274
HIF1 affects OTUD6B
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HIF1 increases the amount of OTUD6B. 1 / 1
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"In addition, inhibition of HIF-1α with HIF-1α inhibitor YC-1 reduced protein levels of Calpain-1 and Otud6b (Fig. 10G-V)."
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HIF affects OTUD6B
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OTUD6B binds HIF. 1 / 1
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sparser
"In the cytoplasm, Otud6b interacts with HIF, which mediates the cell’s transcriptional response to hypoxia."
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"In addition, the differential expression levels of lncRNAs included TSIX, NRIR, ncRNA00201, OTUD6B-AS, CTBP1-AS2, AGAP2-AS1, and HIFA-AS1, which can target mRNAs and might also involve pathogenesis and pathological changes in patients with SSc."
| PMC
Delta-actitoxin-Avd1a affects mtf1
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Delta-actitoxin-Avd1a binds OTUD6B and mtf1. 1 / 1
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"As shown in xref , the luciferase activity driven by the WT promoter sequence was markedly reduced by MTF1 knockdown, indicating that the WT sites are required for binding of MTF1 to the lncRNA OTUD6B-AS1 promoter."
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Calpain-1 KO mice affects OTUD6B
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Calpain-1 KO mice decreases the amount of OTUD6B. 1 / 1
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"Calpain-1 KO mice and Calpain-1 inhibitor MDL inhibited Calpain-1 protein expression, decreased Otud6b protein expression, and further improved PAH."
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CTBP1 affects OTUD6B
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sparser
"In addition, the differential expression levels of lncRNAs included TSIX, NRIR, ncRNA00201, OTUD6B-AS, CTBP1-AS2, AGAP2-AS1, and HIFA-AS1, which can target mRNAs and might also involve pathogenesis and pathological changes in patients with SSc."
| PMC
CSF3 affects OTUD6B
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CSF3 decreases the amount of OTUD6B. 1 / 1
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"However, granulocyte colony stimulating factor (G-CSF) could effectively down-regulate OTUD-6B expression when human leukocytes were stimulated for 16 hours XREF_BIBR."
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CSF2 affects OTUD6B
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CSF2 activates OTUD6B. 1 / 1
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"Here we report that Otud-6b, a functional DUB of the OTU family, can be induced by IL-3, IL-4, IL-13 and granulocyte-macrophage colony stimulating factor (GM-CSF) stimulation in B lymphocytes."
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CAPN1 affects OTUD6B
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CAPN1 decreases the amount of OTUD6B. 1 / 1
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"Compared with hypoxia group, hypoxia + Calpain-1 knockout group not only improved the pathological changes of PAH, but also significantly reduced the protein expression of Otud6b, suggesting that Calpain-1 plays an important role in the regulation of Otud6b.Calpain is a conservative family of calcium dependent cysteine proteases that are commonly expressed in all cells [16, 17]."
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sparser
"In addition, the differential expression levels of lncRNAs included TSIX, NRIR, ncRNA00201, OTUD6B-AS, CTBP1-AS2, AGAP2-AS1, and HIFA-AS1, which can target mRNAs and might also involve pathogenesis and pathological changes in patients with SSc."
| PMC