IndraLab

Statements

OTUB2 is modified
| 1 54 1
OTUB2 is sumoylated.
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OTUB2 is sumoylated. 10 / 44
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"Targeting OTUB2 sumoylation could reduce its ability to interact with YAP/TAZ, resulting in YAP/TAZ degradation."
31832513
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"A yet-unknown SUMO-interacting motif (SIM) in YAP and TAZ was required for the association of YAP/TAZ with SUMOylated OTUB2."
36264492
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"Importantly, EGF and oncogenic KRAS induce OTUB2 poly-SUMOylation and thereby activate YAP/TAZ."
36264492
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"Accordingly, we found the EGF stimulation, but not the treatment of other cytokines, specifically induced OTUB2 SUMOylation ( Figure 7 B); this was confirmed in PLA analysis ( Figure S7 A)."
30472188
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"In addition, sumoylation of OTUB2, a deubiquitinase participating in the maintenance of several CSCs, enables its interaction with transcriptional regulators YAP/TAZ to activate YAP/TAZ signaling and promote cancer cell stemness ( xref )."
36601585
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"Poly-SUMOylated OTUB2, which was induced by Epidermal growth factor (EGF) and oncogenic KRAS, was shown to bind and activate YAP/TAZ promoting tumor metastasis [ xref ]."
31619007
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"KRAS has been shown to indirectly activate Yes-associated protein (YAP), the downstream effector of the Hippo pathway, by inducing OTUB2 poly-SUMOylation, which can regulate gene expression and cellular proliferation xref ."
38481800
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"The levels of SUMOylated OTUB2 were significantly higher in KRAS-high and KRAS-mutated samples, and they were positively correlated with the levels of YAP and TAZ ( Figures 7 I, 7J, and S7 E)."
30472188
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"Thus, these clinical data support our model that EGF signaling or RAS activation stimulates OTUB2 SUMOylation and thereby stabilizes YAP/TAZ, which enhances cancer stemness and metastasis ( Figure 7 K[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
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"The OTUB2 SUMOylation site is located in the last five amino acid residues, which have been reported to cause OTUB2 self-inhibition ( Balakirev et al., 2003 )."
30472188
OTUB2 is sumoylated on K233. 7 / 7
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"Nowadays, for the modification regulation of OTUB2, only SUMOylation of the Lys233 site of OTUB2 is confirmed to interact with Yes-associated protein/transcriptional co-activator with PDZ-binding motif (YAP/TAZ), thereby enhancing the activity of OTUB2 and mediating the transfer of ubiquitin ( xref )."
35309903
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"In mouse breast cancer cells, OTUB2 is SUMOylated at the Lys233 site after translation, and modified OTUB2 relies on this modification to interact with SUMO-interacting motif (SIM) of YAP/TAZ to perform its deubiquitination function, ultimately affecting cancer metastasis ( xref )."
35309903
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"Interestingly, OTUB2 is sumoylated on Lys 233, which promotes its association with Yap/Taz via a conserved but previously uncharacterized SUMO-interacting motif (SIM) in Yap/Taz ( xref )."
33869224
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"Ovarian tumor (OTU) domain-containing ubiquitin aldehyde-binding protein 2 (OTUB2) is an active-site cysteine containing DUB. xref Recent research progress revealed that elevated OTUB2 expression correlates with tumorigenesis and metastasis. xref − xref OTUB2 can promote tumorigenic progression of non-small cell lung cancer cells through deubiquitination of U2AF2, stimulation of the Warburg effect, and activation of AKT/mTOR signaling. xref Moreover, OTUB2 has been identified as a cancer stemness and metastasis-promoting factor that deubiquitinates YAP/TAZ proteins in breast cancer cells, whereby poly-SUMOylation on OTUB2 lysine 233 mediates the interaction with YAP/TAZ. xref These studies demonstrate OTUB2 to be a relevant therapeutic target, and the development of OTUB2-specific inhibitors can potentially be beneficial for cancer therapies."
37642399
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"Furthermore, the SUMOylation of OTUB2 at Lys-233 facilitates its interaction with YAP/TAZ and augments its deubiquitinating activity xref ."
38572092
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"OTUB2, a deubiquitinating cysteine protease, has been shown to deubiquitinate and activate YAP/TAZ in RAS-transformed MCF10A cells, which is dependent on poly-SUMOylation of OTUB2 on lysine 233 ( xref ) [ xref ]."
36264492
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"For instance, SUMOylation of the deubiquitinating enzyme OTUB2 at K233 heightens its interaction with YAP/TAZ and stabilizes YAP/TAZ via deubiquitination, contributing to cancer metastasis xref ."
38855173
OTUB2 is ubiquitinated.
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OTUB2 is ubiquitinated. 4 / 4
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"Given that PbE3‐2 ubiquitinates RD21A and OTU2 interacts with RD21A, we hypothesized that OTU2 may interfere with the interaction between PbE3‐2 and RD21A. The Y3H experiment results supported this hypothesis, showing that OTU2 blocks the interaction between PbE3‐2 and RD21A. As shown in Figure  xref , yeast colonies carrying the PbE3‐2 and RD21A constructs grew on the defective medium, whereas colonies with an additional OTU2 construct did not, indicating that OTU2 disrupts this interaction."
40223806
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"We next set out to identify which amino acid(s) is/are ubiquitinated in GFP-OTUB2."
37642399
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"In the present study, we provided mechanistic insights into TRIM47 as an important regulator of the Warburg effect by its inhibition of OTUB2’s ubiquitination."
33529753
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"Altogether these data demonstrate that OTUB2 is ubiquitinated via lysine 31 and that inactivation of OTUB2 by catalytic site mutation or inhibitor treatment leads to elevated monoubiquitination."
37642399
OTUB2 is phosphorylated.
| 1
OTUB2 is phosphorylated on S65. 1 / 1
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"Ser65 phosphorylation increased OTUB2-mediated cleavage of K48-linked Ub, but it decreased OTUB2-mediated cleavage of K63 linkages (Figure 6N)."
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OTUB2 affects YAP1
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OTUB2 binds YAP1.
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YAP1 binds OTUB2. 10 / 20
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"For example, poly-SUMOylated OUTB2 induced by EGF/KARS was required for interaction between OTUB2 and YAP/TAZ and subsequently YAP/TAZ stabilization by OTUB2 deubiquitination [16]."
35931679
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"Mechanistically, OTUB2 bound to YAP, decreasing its K48-linked polyubiquitination and inhibiting its subsequent degradation."
39776804
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"Not limited to cancer, the latest research has shown that pantoprazole promotes the degradation of YAP and finally blocks the progress of liver fibrosis by breaking the interaction between OTUB2 and YAP, which indirectly demonstrates that OTUB2 contributes to the progression of liver fibrosis ( xref )."
35309903
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"We then confirmed that OTUB2 interacted with YAP through endogenous Co-IP assays, and the exogenous interaction between OTUB2 and YAP was further confirmed in HEK293T cells transfected with Flag-tagged OTUB2 and HA-tagged YAP (Figure xref B)."
39776804
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"Previous reports have suggested that interactions between OTUB2 and YAP require SUMO modification xref ."
39776804
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"PPZ also disrupted the interaction between the deubiquitinating enzyme OTUB2 and YAP , leading to YAP destabilization and impeding hepatic fibrosis progression ( xref )."
39479501
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"The results revealed that the OTU domain was necessary for the interaction of OTUB2 with YAP, whereas the TBD domain was required for the interaction of YAP with OTUB2 (Figure xref K-L)."
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"OTUB2 can both bind and deubiquitinate and thereby stabilize YAP and TAZ, particularly in cancer cells expressing oncogenic KRAS."
30472188
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No evidence text available
30472188
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"A previous study revealed a crucial role for SUMOylation in the interaction between OTUB2 and YAP xref ."
39776804
OTUB2 activates YAP1.
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OTUB2 activates YAP1. 10 / 17
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"OTUB2 activates YAP in VSMCs."
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"Zhang et al. [12] demonstrated that OTUB2 promoted tumor metastasis by independently activating YAP and TAZ."
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"Notably, OTUB2 deficiency also resulted in severely decreased expression of YAP/TAZ target gene signature ( Li et al., 2017 ) ( Figure 2 C), which was confirmed in qRT-PCR assays ( Figure S3 B), sugge[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
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"OTUB2 activates YAP protein by direct deubiquitination and stabilization [47]."
35606801
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"In addition, sumoylation of OTUB2, a deubiquitinase participating in the maintenance of several CSCs, enables its interaction with transcriptional regulators YAP/TAZ to activate YAP/TAZ signaling and promote cancer cell stemness (Zhang et al., 2019)."
36601585
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"Since OTUB2 modulates YAP activity and VC progression, we next sought to investigate the potential regulatory mechanisms between OTUB2 and YAP."
39776804
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"A protein half-life assay revealed that OTUB2 knockdown decreased YAP protein stability in VSMCs (Figure 5G)."
39776804
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"Conversely, OTUB2 overexpression increased the stability of YAP (Figure 5H)."
39776804
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"These observations indicate that the OTUB2-induced cancer stem cell traits might be a result of YAP/TAZ activation."
30472188
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"In the present study, we found that OTUB2-mediated YAP stabilization promotes PFKFB3 transcription, thereby accelerating VC in CKD."
39776804
OTUB2 deubiquitinates YAP1.
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OTUB2 deubiquitinates YAP1. 8 / 8
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"Taken together, these data suggest that OTUB2 deubiquitylates YAP and promotes its stability in VSMCs."
39776804
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"Another three DUBs, ubiquitin carboxyl-terminal hydrolase 10 (USP10), otubain-2 (OTUB2) and ubiquitin carboxyl-terminal hydrolase 47 (USP47) deubiquitinate YAP/TAZ, playing important roles in hepatocellular carcinoma, breast cancer and colorectal cancer, respectively21 32 33."
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"As shown, KRAS expression diminished YAP/TAZ poly-ubiquitination in control HEK293T cells, but not in OTUB2-depleted cells ( Figure S7 B), confirming that OTUB2 mediates YAP/TAZ deubiquitination by RA[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
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"OTUB2 activates YAP/TAZ by directly deubiquitinating and stabilizing both YAP and TAZ."
30472188
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"Deubiquitination of YAP/TAZ by OTUB2 depends on the presence of a poly-SUMO chain conjugated to OTUB2 lysine 233, as SUMOylation enables OTUB2 interaction with a novel SUMO-interacting motif (SIM) ide[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
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"OTU deubiquitinase, ubiquitin aldehyde binding 2 (OTUB2) promotes tumor stemness and metastasis by deubiquitinating and activating YAP/TAZ through a Hippo-independent pathway [ 24 ]."
38537774
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"Complementary, depletion of endogenous OTUB2 increased YAP/TAZ ubiquitination ( Figure S4 D)."
30472188
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"Mechanistically, OTUB2 deubiquitylated YAP and promoted its nuclear translocation, leading to increased PFKFB3 expression."
39776804
OTUB2 increases the amount of YAP1.
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OTUB2 increases the amount of YAP1. 5 / 5
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"The regulation of YAP expression by OTUB2 was also validated through an in vivo animal study, and the results were consistent with those of the in vitro experiments (Figure 3N and Figure S4D)."
39776804
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"Moreover, we detected strong YAP/TAZ protein levels in the metastatic nodules from the lung and brain of the OTUB2 group ( Figure 2 K), suggesting that OTUB2 can increase the levels of YAP/TAZ."
30472188
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"This phenomenon indicated that OTUB2 may promoting YAP1 and TAZ protein expression during the development of ESCC, and the role of OTUB2 in promoting the development of ESCC may mainly occur via YAP1 and TAZ."
35850645
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"Additionally, overexpression of OTUB2 upregulated YAP expression in a dose-dependent manner but did not affect the expression levels of upstream components of the Hippo pathway, such as LATS1, in either VSMCs or HEK293T cells (Figure 3H and Figure S4C)."
39776804
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"OTUB2 silencing decreased the YAP protein level, whereas MG132, but not leupeptin, abrogated this decrease (Figure 5E-F)."
39776804
OTUB2 inhibits YAP1.
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OTUB2 inhibits YAP1. 2 / 2
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"OTUB2 knockdown in ESCC cell lines suppressed YAP1/TAZ signaling."
35850645
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"Gene expression profiling showed that nearly all the OTUB2-stimulated YAP/TAZ target genes were inhibited by VP treatment ( Figures 2 F and S3 D)."
30472188
OTUB2 affects CD274
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OTUB2 binds CD274.
| 7 17
OTUB2 binds CD274. 10 / 23
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"The compound OTUB2-IN1-1 inhibits the deubiquitinase activity of OTUB2 without affecting the physical interaction between OTUB2 and PD-L1."
39223632
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"OTUB2 directly bound to PD-L1, hindering its ubiquitination and subsequent degradation within the endoplasmic reticulum."
38638430
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"Next, we characterized the interaction between OTUB2 and PD-L1."
38167274
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"To ensure that the ability of OTUB2-IN-1 to reduce PD-L1 expression was due to the impaired deubiquitinase activity of OTUB2 rather than the impaired binding of OTUB2 to PD-L1, we further verified the ability of OTUB2-IN-1 to block the binding of OTUB2 to PD-L1 using a blocking chemiluminescence immunoassay (CLIA) and a co-IP assay."
38167274
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"We found that OTUB2-IN-1 did not interfere with protein interactions between OTUB2 and PD-L1 (Fig. 9g and Supplementary Fig. 21)."
38167274
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"The effects of OTUB2-IN-1 on blocking the interactions between OTUB2 and PD-L1 was determined by an indirect CLIA."
38167274
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"To detect the interaction between OTUB2 and PD-L1, we used a Duolink® in situ PLA kit (Sigma‒Aldrich, DUO92101)."
38167274
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"OTUB2 directly bound to PD-L1, hindering its ubiquitination and subsequent degradation within the endoplasmic reticulum."
38638430
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"Mechanistically, OTUB2 directly interacts with PD-L1 to disrupt the ubiquitination and degradation of PD-L1 in the endoplasmic reticulum."
38167274
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"An inhibitor of OTUB2, interfering with its deubiquitinase activity without disrupting the OTUB2-PD-L1 interaction, successfully reduces PD-L1 expression in tumor cells and suppressed tumor growth."
38167274
OTUB2 binds CD274 and orange. 1 / 1
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"We found that the interaction between OTUB2 and PD-L1 (orange signals) mainly colocalized with the ER marker calnexin (Fig. 6b)."
38167274
OTUB2 deubiquitinates CD274.
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OTUB2 deubiquitinates CD274. 6 / 6
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"Mechanistically, OTUB2 directly interacts with PD-L1 to disrupt the ubiquitination and degradation of PD-L1 in the endoplasmic reticulum."
38167274
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"To determine whether OTUB2-mediated PD-L1 stabilization is regulated by deubiquitination, we asked whether OTUB2 deubiquitinates PD-L1 to increase protein stability."
38167274
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"We analyzed PD-L1 ubiquitination in the presence of the proteasome inhibitor MG132 and found that MG132-induced PD-L1 ubiquitination was abolished by OTUB2 OE (Fig. 4a)."
38167274
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"We found that OTUB2 reduced the endogenous K48-linked polyubiquitination of PD-L1 but had no effect on K63-linked polyubiquitination (Fig. 4f, g)."
38167274
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"We constructed two mutants, PD-L1ΔICD (devoid of the ICD) and PD-L1 3KR (three lysine residues were mutated to arginine), and examined whether OTUB2 could still reduce the polyubiquitination of PD-L1."
38167274
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"OTUB2 can interact with PD-L1 and deubiquitinate and stabilize the PD-L1 protein by intervening in the ERAD pathway."
38167274
OTUB2 increases the amount of CD274.
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OTUB2 increases the amount of CD274. 5 / 5
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"Genetic deletion of OTUB2 markedly decreases the expression of PD-L1 proteins on the tumor cell surface, resulting in increased tumor cell sensitivity to CD8 + T-cell-mediated cytotoxicity."
38167274
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"On the structural basis of the binding pocket of OTUB2, we identify OTUB2-IN-1, a specific inhibitor of OTUB2, which can reduce the expression of PD-L1 proteins in tumor cells and suppress tumor growth by promoting robust intra-tumoral infiltration of CTLs."
38167274
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"In contrast, OTUB2 OE in lung cancer cells enhanced both endogenous PD-L1 expression and IFN-γ-induced PD-L1 expression (Fig. 3d−f and Supplementary Fig. 9a, b)."
38167274
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"Consistently, introduction of OTUB2-WT but not OTUB2-C51S enhanced both endogenous PD-L1 expression and IFN-γ-induced PD-L1 expression (Fig. 3d−f and Supplementary Fig. 9a, b)."
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"In this study, we found that OTUB2 inhibition may also inhibit cancer progression by suppressing Hippo signaling, AKT/mTOR signaling and NF-κB signaling in addition to the reduction of PD-L1 expression."
38167274
OTUB2 activates CD274.
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OTUB2 activates CD274. 4 / 4
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"In this study, we demonstrate OTUB2-mediated PD-L1 regulation as a common feature in various human and mouse cancers, particularly in NSCLC."
38167274
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"Given the important role of OTUB2-mediated PD-L1 stability in suppression of tumor growth, we reasoned that targeting OTUB2 could be beneficial in the treatment of cancer."
38167274
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"To further explore the cellular location at which OTUB2 prevents the proteasomal degradation of PD-L1, we performed immunofluorescence (IF) following Duolink in situ PLAs using antibodies targeting different organelles to confirm the subcellular location of the OTUB2–PD-L1 interaction."
38167274
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"To determine whether OTUB2-mediated PD-L1 stabilization is regulated by deubiquitination, we asked whether OTUB2 deubiquitinates PD-L1 to increase protein stability."
38167274
OTUB2 inhibits CD274.
| 3
OTUB2 inhibits CD274. 3 / 3
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"Additionally, Ren et al. demonstrated that the pharmacological targeting of OTUB2 promotes PD-L1 degradation, increasing the sensitivity of tumor cells to T cells."
40130728
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"These results indicate that depletion of OTUB2 enhances antitumor immunity by regulating PD-L1 abundance and activating CTLs."
38167274
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"OTUB2 mediates ER-dependent degradation of PD-L1."
38167274
OTUB2 decreases the amount of CD274.
| 2
OTUB2 decreases the amount of CD274. 2 / 2
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"Western blot analysis of cellular lysates confirmed that OTUB2 KD or KO induced a decrease in the PD-L1 protein level, while OTUB2-WT but not OTUB2-C51S overexpression caused an increase (Fig. 3h, i and Supplementary Fig. 11a−f)."
38167274
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"An inhibitor of OTUB2, interfering with its deubiquitinase activity without disrupting the OTUB2-PD-L1 interaction, successfully reduces PD-L1 expression in tumor cells and suppressed tumor growth."
38167274
OTUB2 affects U2AF2
4 | 17 9
OTUB2 binds U2AF2.
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OTUB2 binds U2AF2. 10 / 20
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"In addition, immunoprecipitation assays using an antibody against endogenous OTUB2 revealed endogenous interactions between OTUB2 and U2AF2 (Figure xref C)."
30662561
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"Furthermore, the interaction between endogenous OTUB2 and U2AF2 was demonstrated by co-immunoprecipitation using an antibody against endogenous U2AF2 in A549 and H1299 cells (Figure xref D)."
30662561
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"These results indicate that OTUB2 specifically interacts with U2AF2 in NSCLC cells."
30662561
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"The interaction between OTUB2 and U2AF2 was verified by co-immunoprecipitation assays in HA-OTUB2-H292 cells (Figure xref B)."
30662561
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"Our data provide ample evidence to demonstrate that OTUB2 binds to U2AF2, efficiently deubiquitinating it by removing the K-48 polyubiquitin chains and protecting it from proteasomal degradation."
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"Similarly, in non-small cell lung cancer, OTUB2 could bind to U2AF2 and deubiquitinate it, making U2AF2 more stable, promoting the Warburg effect of tumors through the AKT/mTOR signaling pathway [54]."
38819228
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"Then the interaction between OTUB2 and U2 small nuclear RNA auxiliary factor 2 (U2AF2) was found through the immunoprecipitation method."
35309903
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No evidence text available
30662561
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"The interaction between OTUB2 and U2AF2 was verified by co-immunoprecipitation assays in HA-OTUB2-H292 cells."
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"In addition, immunoprecipitation assays using an antibody against endogenous OTUB2 revealed endogenous interactions between OTUB2 and U2AF2."
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OTUB2 binds U2AF2 and PGK1. 2 / 2
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"High expression of OTUB2, U2AF2 and PGK1 is significantly associated with worse prognosis in NSCLC patients."
30662561
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"In addition, our results suggest that high expression of OTUB2, U2AF2 and PGK1 is significantly associated with worse prognosis in NSCLC patients."
30662561
OTUB2 deubiquitinates U2AF2.
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OTUB2 deubiquitinates U2AF2. 3 / 3
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"OTUB2 knockdown significantly enhanced the levels of U2AF2 ubiquitination and K48 linked polyubiquitin chains in H1299 cells, whereas OTUB2 overexpression significantly reduced the levels of U2AF2 ubiquitination and K48 linked polyubiquitin chains in XL-2 cells."
30662561
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"This finding led us to hypothesize that OTUB2 directly interacts with and deubiquitinates U2AF2."
30662561
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"Of note, U2AF2 deubiquitination by OTUB2 is important for U2AF2 stabilization."
30662561
OTUB2 activates U2AF2.
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OTUB2 activates U2AF2. 3 / 3
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"OTUB2 increases the activity of the glycolytic enzyme PGK1 and activates Akt/mTOR signalling pathways to promote the Warburg effect in NSCLC by stabilising U2AF2 [49] ."
35031261
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"Taken together, these results indicate that OTUB2 promotes xenograft tumor growth of NSCLC cells by stabilizing U2AF2 and enhancing the Warburg effect In vivo."
30662561
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"Consistently, OTUB2 overexpression in XL-2 and H292 cells increased the half-life of U2AF2 protein in the presence of CHX."
30662561
OTUB2 decreases the amount of U2AF2.
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OTUB2 decreases the amount of U2AF2. 2 / 2
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"We first examined the mRNA and protein levels of U2AF2 following OTUB2 knockdown or overexpression in MG132 treated NSCLC cell lines wherein global proteasomal activity was inhibited."
30662561
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"Knockdown of OTUB2 significantly inhibited the U2AF2 protein levels in A549 and H1299 cells but had no impact on U2AF2 mRNA levels."
30662561
OTUB2 affects TRAF6
3 1 | 1 18 5
OTUB2 binds TRAF6.
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OTUB2 binds TRAF6. 10 / 11
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"This analysis revealed a potential interaction between OTUB2 and TRAF6 ( xref ), and subsequent studies confirmed that TRAF6 is a substrate of OTUB2."
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No evidence text available
19996094
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"These results demonstrated that TRAF6 binding to OTUB2 is crucial for its induction of autophagy and selective autophagic CTNNB1 degradation."
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"OTUB1 and OTUB2 interact with and deubiquitinate TRAF3 and TRAF6, which are required for virus triggered IRF3 and NF-kappaB activation [XREF_BIBR]."
23151130
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"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63 linked polyubiquitin chains."
33511009
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"More than this special feature, if OTUB2 interacts with TRAF6, the result should benefit the NF-kappaB pathway."
35309903
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No evidence text available
23105109
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"This analysis revealed a potential interaction between OTUB2 and TRAF6 (Fig. 5A), and subsequent studies confirmed that TRAF6 is a substrate of OTUB2."
40296903
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"Therewith, we demonstrated the exogenous binding between OTUB2 and TRAF6 in HEK293T cells by Co-immunoprecipitation (Co-IP) assays (Fig. 5B)."
40296903
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"These results demonstrated that TRAF6 binding to OTUB2 is crucial for its induction of autophagy and selective autophagic CTNNB1 degradation."
36858343
OTUB1 binds OTUB2, TRAF3, and TRAF6. 1 / 1
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"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63‐linked polyubiquitin chains. [ xref ] Because various components are involved in virus‐induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG‐I‐, MDA5‐, and MAVS‐mediated but not TBK1‐ and IRF3‐mediated signaling."
33511009
OTUB2 deubiquitinates TRAF6.
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OTUB2 deubiquitinates TRAF6. 10 / 11
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"Regulation of virus-triggered signaling by OTUB1- and <span class="match term0">OTUB2</span>-mediated deubiquitination of TRAF3 and <span class="match term1">TRAF6</span>"
19996094
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"OTUB2 promotes proliferation and metastasis of triple-negative breast cancer by deubiquitinating TRAF6."
40296903
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"OTUB2 deubiquitinates TRAF6 and activates AKT."
40296903
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"Therefore, we examined the effects of OTUB2 on TRAF6 ubiquitination and found that OTUB2 overexpression reduced the polyubiquitination of TRAF6 (Fig. 5E)."
40296903
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"Based on these findings, we hypothesized that OTUB2 activates AKT by deubiquitinating TRAF6, thereby exerting a pro-oncogenic effect."
40296903
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"OTUB1 and OTUB2 interact with and deubiquitinate TRAF3 and TRAF6, which are required for virus triggered IRF3 and NF-kappaB activation [XREF_BIBR]."
23151130
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"The experimental results further confirmed that OTUB2 reduced the ubiquitination of TRAF6, thereby positively regulating its protein expression.Previous studies have shown that AKT signaling plays a pivotal role in various biological processes, including cell proliferation, invasion and apoptosis [44]."
40296903
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"It was also shown that two OTUB deubiquitinating enzyme family members, OTUB1 and OTUB2, can deubiquitinate TRAF3 and TRAF6, leading to the inhibition of virus induced IFN-beta expression and cellular antiviral responses."
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"OTUB1 and OTUB2 regulate virus-triggered IFN inflammation by deubiquitinating TRAF3 and TRAF6 [75]."
32650621
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"OTUB1 and OTUB2, which are members of the OTUB deubiquitinase superfamily, may deubiquitinate TRAF3 and TRAF6, stop SeV-induced NF-κB and IRF3 activation, and aid in viral replication [41] ."
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OTUB2 inhibits TRAF6.
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OTUB2 inhibits TRAF6. 4 / 4
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"TRAF3 and TRAF6 are both deactivated by the DUbs otubain 1 ( OTUB1 ) and OTUB2 , which remove K63-linked polyubiquitin chains ( Li et al ., 2010b ) ."
26712804
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"TRAF3 and TRAF6 are both deactivated by the DUbs otubain 1 (OTUB1) and OTUB2, which remove K63 linked polyubiquitin chains."
26712804
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"TRAF6 are inhibited by A20, CYLD and OTUB2 that specially remove TRAF6 K63‐linked ubiquitination."
28744851
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"TRAF6 are inhibited by A20, CYLD and OTUB2 that specially remove TRAF6 K63‐linked ubiquitination."
28744851
OTUB2 increases the amount of TRAF6.
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OTUB2 increases the amount of TRAF6. 1 / 1
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"Furthermore, we observed that overexpression of OTUB2 increased the protein levels of TRAF6 in a dose-dependent manner, although it did not affect TRAF6 mRNA expression (Fig. 5C,D, Fig. S2A), indicating that OTUB2 regulates TRAF6 expression at the post-transcriptional level."
40296903
YAP1 affects OTUB2
3 | 15 8
YAP1 binds OTUB2.
3 | 9 8
YAP1 binds OTUB2. 10 / 20
3 | 9 8
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"For example, poly-SUMOylated OUTB2 induced by EGF/KARS was required for interaction between OTUB2 and YAP/TAZ and subsequently YAP/TAZ stabilization by OTUB2 deubiquitination [16]."
35931679
sparser
"Mechanistically, OTUB2 bound to YAP, decreasing its K48-linked polyubiquitination and inhibiting its subsequent degradation."
39776804
sparser
"Not limited to cancer, the latest research has shown that pantoprazole promotes the degradation of YAP and finally blocks the progress of liver fibrosis by breaking the interaction between OTUB2 and YAP, which indirectly demonstrates that OTUB2 contributes to the progression of liver fibrosis ( xref )."
35309903
sparser
"We then confirmed that OTUB2 interacted with YAP through endogenous Co-IP assays, and the exogenous interaction between OTUB2 and YAP was further confirmed in HEK293T cells transfected with Flag-tagged OTUB2 and HA-tagged YAP (Figure xref B)."
39776804
sparser
"Previous reports have suggested that interactions between OTUB2 and YAP require SUMO modification xref ."
39776804
sparser
"PPZ also disrupted the interaction between the deubiquitinating enzyme OTUB2 and YAP , leading to YAP destabilization and impeding hepatic fibrosis progression ( xref )."
39479501
sparser
"The results revealed that the OTU domain was necessary for the interaction of OTUB2 with YAP, whereas the TBD domain was required for the interaction of YAP with OTUB2 (Figure xref K-L)."
39776804
reach
"OTUB2 can both bind and deubiquitinate and thereby stabilize YAP and TAZ, particularly in cancer cells expressing oncogenic KRAS."
30472188
biogrid
No evidence text available
30472188
sparser
"A previous study revealed a crucial role for SUMOylation in the interaction between OTUB2 and YAP xref ."
39776804
YAP1 activates OTUB2.
| 4
YAP1 activates OTUB2. 4 / 4
| 4
reach
"Conversely, in VSMCs cotransfected with the OTUB2 siRNA (siOTUB2) and a YAP overexpression plasmid (pcYAP), the upregulation of YAP signifi-cantly increased calcium deposition and abrogated the anticalcification effects of OTUB2 knockdown (Figure S5F-H)."
39776804
reach
"We also found that knockdown or inhibition of YAP partly abrogated the procalcific effect of OTUB2 on VC models both in vivo and in vitro."
39776804
reach
"We performed functional rescue experiments to determine whether YAP mediates OTUB2-regulated VSMC osteogenic transdifferentiation."
39776804
reach
"YAP knockdown or inhibition effectively antagonized the OTUB2-mediated increase in osteogenic differentiation (Figure 4I, 4K and Figure S5E)."
39776804
YAP1 increases the amount of OTUB2.
| 1
YAP1 increases the amount of OTUB2. 1 / 1
| 1
reach
"Knockdown or inhibition of YAP abolished the effect of OTUB2 overexpression on VSMC calcification, indicating a YAP-mediated mechanism."
39776804
YAP1 deubiquitinates OTUB2.
| 1
YAP1 leads to the deubiquitination of OTUB2. 1 / 1
| 1
reach
"As for breast cancer, a recent study reported that OTUB2 deubiquitinated and activated YAP/TAZ to promote cancer stemness and metastasis (Zhang et al., 2019), which confirms the reliability of our results."
36685836
OTUB2 activates cell population proliferation. 10 / 23
| 23
reach
"Knockdown of OTUB2 inhibits breast cancer cell proliferation and migration."
39115875
reach
"OTUB2 regulates KRT80 stability via deubiquitination and promotes tumour proliferation in gastric cancer."
35110531
reach
"OTUB2 depletion by two independent shRNAs promoted the proliferation of OVCA429 cells (Fig. 2G and SI Appendix, Fig. S2 F and H)."
38701117
reach
"The overexpression of OTUB2 promoted glycolysis and induced the proliferation, migration, and invasion of endometrial cancer cells."
36316812
reach
"Correction: OTUB2 regulates KRT80 stability via deubiquitination and promotes tumour proliferation in gastric cancer."
35440577
reach
"We also confirmed that OTUB2 enhanced the proliferation, migration, and invasion abilities of NSCLC cells In vitro."
30662561
reach
"Correction: OTUB2 regulates KRT80 stability via deubiquitination and promotes tumour proliferation in gastric cancer."
38191514
reach
"The plate clone formation assay showed that compared with the control group, the clone formation ability of KYSE150 and shNC was significantly decreased and the number of cells was decreased (P < 0.05), which suggested that the proliferation of ESCC could be inhibited by OTUB2 knockdown (Fig. 8B, C)."
35850645
reach
"These authors found that OTUB2 could directly act on YAP1/TAZ independently of the Hippo signaling pathway to promote tumor proliferation."
35850645
reach
"OTUB2 Promotes Proliferation and Migration of Hepatocellular Carcinoma Cells by PJA1 Deubiquitylation."
35611163
reach
"Our results showed that OTUB2 could be stabilized by TRIM47, and the overexpression of OTUB2 rescued the inhibition of cell proliferation and aerobic glycolysis mediated by TRIM47 downregulation."
33529753
reach
"Overexpression of OTUB2 in ES-2 and A2780 cells significantly reduced cell proliferation (Fig. 2F and SI Appendix, Fig. S2 E and G)."
38701117
CD274 affects OTUB2
| 7 17
OTUB2 binds CD274. 10 / 23
| 6 17
sparser
"The compound OTUB2-IN1-1 inhibits the deubiquitinase activity of OTUB2 without affecting the physical interaction between OTUB2 and PD-L1."
39223632
reach
"OTUB2 directly bound to PD-L1, hindering its ubiquitination and subsequent degradation within the endoplasmic reticulum."
38638430
reach
"Next, we characterized the interaction between OTUB2 and PD-L1."
38167274
reach
"To ensure that the ability of OTUB2-IN-1 to reduce PD-L1 expression was due to the impaired deubiquitinase activity of OTUB2 rather than the impaired binding of OTUB2 to PD-L1, we further verified the ability of OTUB2-IN-1 to block the binding of OTUB2 to PD-L1 using a blocking chemiluminescence immunoassay (CLIA) and a co-IP assay."
38167274
reach
"We found that OTUB2-IN-1 did not interfere with protein interactions between OTUB2 and PD-L1 (Fig. 9g and Supplementary Fig. 21)."
38167274
reach
"The effects of OTUB2-IN-1 on blocking the interactions between OTUB2 and PD-L1 was determined by an indirect CLIA."
38167274
reach
"To detect the interaction between OTUB2 and PD-L1, we used a Duolink® in situ PLA kit (Sigma‒Aldrich, DUO92101)."
38167274
sparser
"OTUB2 directly bound to PD-L1, hindering its ubiquitination and subsequent degradation within the endoplasmic reticulum."
38638430
sparser
"Mechanistically, OTUB2 directly interacts with PD-L1 to disrupt the ubiquitination and degradation of PD-L1 in the endoplasmic reticulum."
38167274
sparser
"An inhibitor of OTUB2, interfering with its deubiquitinase activity without disrupting the OTUB2-PD-L1 interaction, successfully reduces PD-L1 expression in tumor cells and suppressed tumor growth."
38167274
OTUB2 binds CD274 and orange. 1 / 1
| 1
reach
"We found that the interaction between OTUB2 and PD-L1 (orange signals) mainly colocalized with the ER marker calnexin (Fig. 6b)."
38167274
U2AF2 affects OTUB2
4 | 10 9
U2AF2 binds OTUB2.
4 | 9 9
OTUB2 binds U2AF2. 10 / 20
4 | 9 7
sparser
"In addition, immunoprecipitation assays using an antibody against endogenous OTUB2 revealed endogenous interactions between OTUB2 and U2AF2 (Figure xref C)."
30662561
sparser
"Furthermore, the interaction between endogenous OTUB2 and U2AF2 was demonstrated by co-immunoprecipitation using an antibody against endogenous U2AF2 in A549 and H1299 cells (Figure xref D)."
30662561
sparser
"These results indicate that OTUB2 specifically interacts with U2AF2 in NSCLC cells."
30662561
sparser
"The interaction between OTUB2 and U2AF2 was verified by co-immunoprecipitation assays in HA-OTUB2-H292 cells (Figure xref B)."
30662561
sparser
"Our data provide ample evidence to demonstrate that OTUB2 binds to U2AF2, efficiently deubiquitinating it by removing the K-48 polyubiquitin chains and protecting it from proteasomal degradation."
30662561
reach
"Similarly, in non-small cell lung cancer, OTUB2 could bind to U2AF2 and deubiquitinate it, making U2AF2 more stable, promoting the Warburg effect of tumors through the AKT/mTOR signaling pathway [54]."
38819228
sparser
"Then the interaction between OTUB2 and U2 small nuclear RNA auxiliary factor 2 (U2AF2) was found through the immunoprecipitation method."
35309903
biogrid
No evidence text available
30662561
reach
"The interaction between OTUB2 and U2AF2 was verified by co-immunoprecipitation assays in HA-OTUB2-H292 cells."
30662561
reach
"In addition, immunoprecipitation assays using an antibody against endogenous OTUB2 revealed endogenous interactions between OTUB2 and U2AF2."
30662561
OTUB2 binds U2AF2 and PGK1. 2 / 2
| 2
sparser
"High expression of OTUB2, U2AF2 and PGK1 is significantly associated with worse prognosis in NSCLC patients."
30662561
sparser
"In addition, our results suggest that high expression of OTUB2, U2AF2 and PGK1 is significantly associated with worse prognosis in NSCLC patients."
30662561
U2AF2 inhibits OTUB2.
| 1
U2AF2 inhibits OTUB2. 1 / 1
| 1
reach
"Importantly, knockdown of U2AF2 rescued the promoting effect of OTUB2 on H292 cell migration and invasion."
30662561
OTUB2 affects RIPK3
| 19 3
OTUB2 activates RIPK3.
| 6
OTUB2 activates RIPK3. 6 / 6
| 6
reach
"Moreover, OTUB2 increased RIPK3 protein abundance by inhibiting the proteasomal degradation of RIPK3."
40021931
reach
"Collectively, these findings show that OTUB2 enhances ischemia-induced neuronal necroptosis by regulating RIPK3 through its DUB activity."
40021931
reach
"Moreover, the protein abundance of RIPK3 was significantly reduced in OTUB2-deficient brains (Fig. 3A,F), suggesting that OTUB2 may modulate the necroptotic signaling by targeting RIPK3."
40021931
reach
"In line with these in vitro results, in the mouse brain, OTUB2 deficiency reduced RIPK3 only at protein levels but not mRNA levels, whereas both protein and mRNA levels of RIPK1 were not altered by OTUB2 deletion (Appendix Fig. S6E–I)."
40021931
reach
"Functionally, deletion of OTUB2 accelerated the degradation of RIPK3 while OTUB2 overexpression delayed RIPK3 degradation (Fig. 4J,K; Appendix Fig. S8)."
40021931
reach
"Given that RIPK3 critically regulates necroptosis and that OTUB2 increases RIPK3 abundance and activity, we then assessed whether OTUB2 enhanced neuronal necroptosis via regulating RIPK3."
40021931
OTUB2 deubiquitinates RIPK3.
| 5
OTUB2 deubiquitinates RIPK3. 3 / 3
| 3
reach
"OTUB2 overexpression reduced the total and K48-specific ubiquitination of RIPK3 (Fig. 5D,E)."
40021931
reach
"LN5P45 treatment reduced RIPK3 protein levels by increasing the K48 ubiquitination of RIPK3, further confirming that OTUB2 deubiquitinates RIPK3 through the enzymatic activity.Pharmacological inhibition of OTUB2 by LN5P45 significantly reduced ischemic stroke injury in mice, indicating that specific and potent OTUB2 inhibitors are competitive candidates for drugs treating ischemic stroke."
40021931
reach
"Deubiquitination of RIPK3 by OTUB2 potentiates neuronal necroptosis after ischemic stroke."
40021931
OTUB2-C51S deubiquitinates RIPK3. 2 / 2
| 2
reach
"We found that the enzymatically inactive OTUB2 C51S mutant failed to deubiquitinate RIPK3, demonstrating that OTUB2 stabilizes RIPK3 through its enzymatic activity."
40021931
reach
"The OTUB2 C51S mutant, which was deprived of the enzymatic activity, failed to K48 deubiquitinate RIPK3 (Fig. 5J)."
40021931
OTUB2 increases the amount of RIPK3.
| 4
OTUB2 increases the amount of RIPK3. 3 / 3
| 3
reach
"Consistently, overexpression of OTUB2 increased RIPK3 protein levels but did not change RIPK1 expression (Fig. 4E; Appendix Fig. S6D)."
40021931
reach
"Importantly, OTUB2 deletion reduced RIPK3 protein levels in HT22 cells (Fig. 3P), consolidating the in vivo findings (Fig. 3A)."
40021931
reach
"Although OTUB2 deletion significantly reduced RIPK3 protein levels in HT22 cells (Fig. 4A,B), OTUB2 deficiency did not change the transcription of Ripk3 mRNA (Fig. 4C), indicating that OTUB2 regulates RIPK3 at post-translational levels."
40021931
OTUB2 increases the amount of phosphorylated RIPK3. 1 / 1
| 1
reach
"Besides, OTUB2 deficiency significantly reduced the levels of phosphorylated RIPK3 and MLKL in primary neurons after OGD (Fig. 6C–F), showing that OTUB2 increases neuronal necroptosis after ischemia."
40021931
OTUB2 binds RIPK3.
| 1 3
OTUB2 binds RIPK3. 4 / 4
| 1 3
sparser
"Together, these results demonstrate that OTUB2 interacts with RIPK3 and increases the protein abundance of RIPK3 by reducing its degradation."
40021931
sparser
"Co-immunoprecipitation (Co-IP) verified the interaction between endogenous RIPK3 and OTUB2 in HT22 cells (Fig.  xref )."
40021931
sparser
"OTUB2 physically interacts with RIPK3 to inhibit its degradation."
40021931
reach
"Co-immunoprecipitation (Co-IP) verified the interaction between endogenous RIPK3 and OTUB2 in HT22 cells (Fig. 4F)."
40021931
OTUB2 inhibits RIPK3.
| 2
OTUB2 inhibits RIPK3. 2 / 2
| 2
reach
"Mechanistically, OTUB2 inhibited the degradation of RIPK3 through removing K48-linked polyubiquitin chains from RIPK3, thereby enhancing RIPK3 abundance and activation."
40021931
reach
"Moreover, OTUB2 increased RIPK3 protein abundance by inhibiting the proteasomal degradation of RIPK3."
40021931
OTUB2 phosphorylates RIPK3.
| 1
OTUB2 leads to the phosphorylation of RIPK3. 1 / 1
| 1
reach
"Although RIPK1 phosphorylation was not changed, OTUB2 deficiency significantly impaired the phosphorylation of RIPK3 and MLKL (Fig. 3A–D)."
40021931
OTUB2 affects TAFAZZIN
| 21
OTUB2 activates TAFAZZIN.
| 8
OTUB2 activates TAFAZZIN. 8 / 8
| 8
reach
"OTUB2 knockdown in ESCC cell lines suppressed YAP1/TAZ signaling."
35850645
reach
"Zhang et al. [12] demonstrated that OTUB2 promoted tumor metastasis by independently activating YAP and TAZ."
39210373
reach
"Notably, OTUB2 deficiency also resulted in severely decreased expression of YAP/TAZ target gene signature ( Li et al., 2017 ) ( Figure 2 C), which was confirmed in qRT-PCR assays ( Figure S3 B), sugge[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
reach
"In addition, sumoylation of OTUB2, a deubiquitinase participating in the maintenance of several CSCs, enables its interaction with transcriptional regulators YAP/TAZ to activate YAP/TAZ signaling and promote cancer cell stemness (Zhang et al., 2019)."
36601585
reach
"These observations indicate that the OTUB2-induced cancer stem cell traits might be a result of YAP/TAZ activation."
30472188
reach
"Taken together, these results support a notion that OTUB2 activates YAP/TAZ signaling and thereby supports cancer stemness and metastasis.We investigated the molecular mechanism by which OTUB2 potenti[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
reach
"Indeed, OTUB2-KO in MCF10A-RAS (MII) cells significantly reduced protein expression of YAP/TAZ and AXL, a downstream target of YAP/TAZ, but had no effect on YAP/TAZ mRNA levels ( Figure 3 B), suggesti[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
reach
"OTUB2 promotes the progression of breast cancer by directly deubiquitinating and stabilizing YAP and TAZ to activate the YAP signalling pathway [9]."
38658981
OTUB2 deubiquitinates TAFAZZIN.
| 7
OTUB2 deubiquitinates TAFAZZIN. 7 / 7
| 7
reach
"Another three DUBs, ubiquitin carboxyl-terminal hydrolase 10 (USP10), otubain-2 (OTUB2) and ubiquitin carboxyl-terminal hydrolase 47 (USP47) deubiquitinate YAP/TAZ, playing important roles in hepatocellular carcinoma, breast cancer and colorectal cancer, respectively21 32 33."
35024322
reach
"As shown, KRAS expression diminished YAP/TAZ poly-ubiquitination in control HEK293T cells, but not in OTUB2-depleted cells ( Figure S7 B), confirming that OTUB2 mediates YAP/TAZ deubiquitination by RA[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
reach
"Recent reports have documented that TAZ can be directly deubiquitinated and stabilized by USP1 [46], USP10 [15], OTUB2 [16] and JOSD2 [47] in hepatocellular carcinoma, breast cancer and cholangiocarcinoma."
35931679
reach
"OTUB2 activates YAP/TAZ by directly deubiquitinating and stabilizing both YAP and TAZ."
30472188
reach
"OTU deubiquitinase, ubiquitin aldehyde binding 2 (OTUB2) promotes tumor stemness and metastasis by deubiquitinating and activating YAP/TAZ through a Hippo-independent pathway [ 24 ]."
38537774
reach
"Deubiquitination of YAP/TAZ by OTUB2 depends on the presence of a poly-SUMO chain conjugated to OTUB2 lysine 233, as SUMOylation enables OTUB2 interaction with a novel SUMO-interacting motif (SIM) ide[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
reach
"Complementary, depletion of endogenous OTUB2 increased YAP/TAZ ubiquitination ( Figure S4 D)."
30472188
OTUB2 increases the amount of TAFAZZIN.
| 3
OTUB2 increases the amount of TAFAZZIN. 3 / 3
| 3
reach
"However, depletion of OTUB2 reduced the YAP/TAZ protein levels both in the wild-type and the LATS1/2 knockout cells, which was not due to changes of YAP/TAZ mRNA levels ( Figure 3 E; data not shown)."
30472188
reach
"Moreover, we detected strong YAP/TAZ protein levels in the metastatic nodules from the lung and brain of the OTUB2 group ( Figure 2 K), suggesting that OTUB2 can increase the levels of YAP/TAZ."
30472188
reach
"This phenomenon indicated that OTUB2 may promoting YAP1 and TAZ protein expression during the development of ESCC, and the role of OTUB2 in promoting the development of ESCC may mainly occur via YAP1 and TAZ."
35850645
OTUB2 binds TAFAZZIN.
| 3
reach
"TIMER database (http://timer.cistrome.org) and the Gene Expression Profiling Interactive Analysis (GEPIA) database (http://gepia.cancer-pku.cn/) were used to search the expression of OTUB2 in esophageal cancer; the GeneMANIA database (http://genemania.org/) was used to search the interaction between OTUB2 and YAP1/TAZ (WWTR1:TAZ also known as WWTR1)."
35850645
reach
"OTUB2 can both bind and deubiquitinate and thereby stabilize YAP and TAZ, particularly in cancer cells expressing oncogenic KRAS."
30472188
reach
"OTUB2 can bind and stabilize YAP1/TAZ through ubiquitination, and has a certain positive regulatory effect on YAP1/TAZ."
35850645
OTUB2 affects RD21A
| 14 7
OTUB2 binds RD21A.
| 2 7
OTUB2 binds RD21A. 7 / 7
| 7
sparser
"To investigate this, we performed a yeast two‐hybrid (Y2H) assay, which confirmed that OTU2 interacts with RD21A but not with PbE3‐2 (Figure  xref ; Figure  xref )."
40223806
sparser
"Consistent with these results, Split‐LUC assays demonstrated that OTU2 interacts with full‐length RD21A (RD21A), intermediate RD21A (iRD21A) and mature RD21A (mRD21A) (Figure  xref )."
40223806
sparser
"To further validate the OTU2–RD21A interaction, we performed a co‐immunoprecipitation (Co‐IP) assay."
40223806
sparser
"Additionally, BiFC assays demonstrated that OTU2 interacts with RD21A in both the cytoplasm and the cell membrane (Figure  xref ; Figure  xref )."
40223806
sparser
"Together, these results confirm that OTU2 interacts with RD21A, highlighting its potential role in counteracting the PbE3‐2‐mediated degradation of RD21A."
40223806
sparser
"To investigate the structural requirements for the interaction between OTU2 and RD21A, we used truncated derivatives of OTU2 in Y2H assays."
40223806
sparser
"We found that RD21A interacts with OTUc (124–208 aa) but not with OTUn (11–123 aa), indicating that the C2H2 zinc finger domain is essential for the interaction between OTU2 and RD21A (Figure  xref )."
40223806
OTUB2 binds RD21A. 2 / 2
| 2
reach
"To investigate the structural requirements for the interaction between OTU2 and RD21A, we used truncated derivatives of OTU2 in Y2H assays."
40223806
reach
"We found that RD21A interacts with OTUc (124–208 aa) but not with OTUn (11–123 aa), indicating that the C2H2 zinc finger domain is essential for the interaction between OTU2 and RD21A (Figure S2c)."
40223806
OTUB2 deubiquitinates RD21A.
| 7
OTUB2 deubiquitinates RD21A. 7 / 7
| 7
reach
"Collectively, our findings demonstrate that OTU2 deubiquitinates RD21A, protecting it from PbE3-2-mediated degradation and thereby mitigating P. brassicae virulence."
40223806
reach
"OTU2 deubiquitinates RD21A, preventing its degradation via the 26S proteasome pathway."
40223806
reach
"OTU2 deubiquitinates RD21A and increases its stability."
40223806
reach
"The results showed that, compared with the control, the presence of OTU2 decreased the amount of RD21A‐FLAG labeled with Ub‐HA, suggesting that OTU2 deubiquitinates RD21A (Figure 3A)."
40223806
reach
"Together, these results suggest that OTU2 increases RD21A protein accumulation by deubiquitinating RD21A, thereby preventing its degradation via the 26S proteasome."
40223806
reach
"Furthermore, OTU2 deubiquitinates RD21A, promoting its accumulation and thereby enhancing A. thaliana resistance to P. brassicae."
40223806
reach
"Furthermore, OTU2 deubiquitinates RD21A both in vitro and in vivo, thereby increasing RD21A stability."
40223806
OTUB2 activates RD21A.
| 5
OTUB2 activates RD21A. 5 / 5
| 5
reach
"Transient expression of PbE3‐2‐GFP, RD21A‐FLAG and OTU2‐Myc in N. benthamiana revealed that OTU2 increased RD21A accumulation compared to the control with an empty vector (Figure S3a), suggesting that OTU2 may protect RD21A from degradation mediated by PbE3‐2."
40223806
reach
"To determine whether OTU2 increases RD21A protein accumulation in A. thaliana, we performed immunoblot analysis using an anti‐RD21A antibody."
40223806
reach
"Considering that OTU2 increases RD21A accumulation, we hypothesized that OTU2 overexpression increases plant resistance against pathogens."
40223806
reach
"OTU2-mediated resistance enhancement requires RD21A ."
40223806
reach
"Further experiments are required to elucidate how OTU2 modulates RD21A stability in the absence of pathogen invasion and whether additional regulatory factors are involved in this process."
40223806
OTUB2 affects glycolytic process
| 18
OTUB2 activates glycolytic process.
| 13
reach
"Fourth, although we determined that OTUB2 promoted glycolysis and increased the lactate content in VSMCs, we did not investigate whether OTUB2 regulates histone lactylation levels during VC progression."
39776804
reach
"In conclusion, circRNA6448-14 sponged miR-455-3p, which in turn promoted OTUB2 expression, thereby enhancing glycolysis and stemness of ESCC cells."
38819228
reach
"In colon cancer, Yu et al. [14] demonstrated that OTUB2 promotes the malignant progression of colorectal cancer by enhancing PKM2 activity and glycolysis."
39210373
reach
"The overexpression of OTUB2 promoted glycolysis and induced the proliferation, migration, and invasion of endometrial cancer cells."
36316812
reach
"Furthermore, the increased glycolysis and decreased OXPHOS mediated by OTUB2 silencing could be effectively reversed by the expression of shRNA-resistant wild-type OTUB2 (SI Appendix, Fig. S4 G–L)."
38701117
reach
"Recent studies have demonstrated that OTUB2 promotes the progression of colorectal cancer by facilitating glycolysis [14]."
39210373
reach
"We assessed the extracellular acidification rate (ECAR) of VSMCs using an XFe96 extracellular flux analyzer to further explore whether OTUB2 mediates glycolysis through PFKFB3."
39776804
reach
"Finally, we revealed that circRNA6448-14 promoted OTUB2 expression and enhanced ESCC glycolysis and stemness by competitively binding to miR-455-3p."
38819228
reach
"In addition, the deubiquitinase OTUB2 enhances glycolysis to aggravate the progression of CRC [27,29]."
38585643
reach
"Here we demonstrate that OTUB2, an OTU deubiquitinase, is upregulated in colorectal cancer (CRC) and exacerbates the progression of CRC through modulating the aerobic glycolysis."
34671086
OTUB2 inhibits glycolytic process.
| 5
OTUB2 inhibits glycolytic process. 5 / 5
| 5
reach
"Having demonstrated that OTUB2/SNX29P2 causes impaired glycolysis and increased OXPHOS in ovarian cancer cells, we then identified the mediator of this function."
38701117
reach
"Activation of CA9 restores OTUB2-mediated inhibition of glycolysis and tumor growth; thus, CA9 inhibitors might be a promising strategy for ovarian cancer treatment."
38701117
reach
"OTUB2/SNX29P2 Suppresses Glycolysis and Promotes OXPHOS in Ovarian Cancer.."
38701117
reach
"The results of gene set enrichment analysis (GSEA) indicated that overexpression of either OTUB2 or SNX29P2 suppresses the glycolysis pathway and enhances OXPHOS activity (Fig. 4 A and B)."
38701117
reach
"Overexpression of OTUB2 or SNX29P2 in ES-2 cells inhibited glycolysis and lactate production while increasing OXPHOS (Fig. 4 C–E and SI Appendix, Fig. S4 A–C)."
38701117
OTUB2 affects Ubiquitin
| 5 9
OTUB2 binds Ubiquitin.
| 2 9
sparser
"A. thaliana OTU2 and OTLD1 bind UB chains with distinct linkage preferences."
24659992
sparser
"Interestingly, there is a novel oxyanion hole inside OTUB2 generated by the active site loop, which may be conducive to the interaction between OTUB2 and ubiquitin ( xref )."
35309903
sparser
"The deleterious effect of NEM on OTU2 UB chain binding indicates that other Cys residues are likely critical."
24659992
sparser
"Among the eleven A. thaliana OTU DUBs examined, we found that OTU2 and OTLD1 bind UB chains with distinct linkage preferences."
24659992
reach
"Structure of human OTUB2 bound to Ub."
25590432
reach
"Since OTUB2 does not have the N-terminal helix and its alpha1alpha2 loop is 2 residues shorter, it is expected that the binding of proximal Ub to OTUB2 is substantially different from OTUB1."
25590432
sparser
"LotA OTU2 binds to positively charged ubiquitin residues (R42, R72, R74) through the acidic patch (D407, D410, D412) on the EHL."
35651329
sparser
"Although the local resolution was lower due to flexibility (4.0–7.0 Å), we observed a clear density for ubiquitin bound to the Otu2 S1 site (Supplementary Figs.  xref , xref , and xref , xref )."
37169754
sparser
"Like in other Ub-binding proteins and OTU domain containing proteins, Otu2 binds to ubiquitin via a conserved hydrophobic region in the S1 site of the OTU domain (Tyr223, Phe225, Leu255) recognizing a corresponding hydrophobic patch in ubiquitin (Leu8, Ile44, Val70), as described before for various types of ubiquitin-binding proteins including the OTU family of DUBs xref , xref , xref – xref (Fig.  xref )."
37169754
sparser
"Structure of human OTUB2 bound to Ub."
25590432
OTUB2 inhibits Ubiquitin.
| 2
OTUB2 inhibits Ubiquitin. 2 / 2
| 2
reach
"The specific ubiquitin chains that OTUB2 could inhibit to exert its deubiquitinating effect on the SP1 protein remain unknown."
39210373
reach
"These data, combined with the observation that NCS induced formation of RAP80 foci was inhibited by OTUB2 overexpression and accelerated by OTUB2 depletion, indicate that OTUB2 negatively regulates DN[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24560272
OTUB2 activates Ubiquitin.
| 1
OTUB2 activates Ubiquitin. 1 / 1
| 1
reach
"OTUB2, as a member of the deubiquitinase family, promotes substrate stability by cleaving ubiquitin chains and exhibits ubiquitin hydrolase activity."
40296903
OTUB2 affects GLI2
3 1 | 5 8
OTUB2 binds GLI2.
3 | 1 8
OTUB2 binds GLI2. 10 / 12
3 | 1 8
biogrid
No evidence text available
30241937
biogrid
No evidence text available
30241937
biogrid
No evidence text available
30241937
sparser
"We provided evidence that OTUB2 binds to and deubiquitinates Gli2, playing a critical role in regulating the Hh signaling pathway."
30241937
sparser
"The authors found that OTUB2 formed a complex with Gli2 and promoted Gli2 deubiquitination both in vitro and in vivo."
| PMC
sparser
"Furthermore, we confirmed that OTUB2 could bind to Gli2, which indicated that Gli2 were substrates for OTUB2."
30241937
sparser
"To identify the interactions between endogenous Gli2 and OTUB2, HEK293A cells were transfected with Flag-tagged OTUB2 construct or vector control, and the cell lysate was subjected to immunoprecipitat[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30241937
sparser
"To identify the interactions between endogenous OTUB2 and Gli2, HEK293A cells were transfected with Flag-tagged Gli2, then the cell lysate was subjected to IP using anti-Flag magnetic beads (M8823, Si[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30241937
reach
"The authors found that OTUB2 formed a complex with Gli2 and promoted Gli2 deubiquitination both in vitro and in vivo."
| PMC
sparser
"Meanwhile, the interaction between OTUB2 and Gli2 was determined by immunoprecipitation ( xref )."
35309903
OTUB2 inhibits GLI2.
| 2
OTUB2 inhibits ubiquitinated GLI2. 1 / 1
| 1
reach
"Invitro deubiquitination assay showed that ubiquitinated Gli2 was decreased by wild-type OTUB2 but not OTUB2 mutations."
30241937
Mutated OTUB2 inhibits ubiquitinated GLI2. 1 / 1
| 1
reach
"Invitro deubiquitination assay showed that ubiquitinated Gli2 was decreased by wild-type OTUB2 but not OTUB2 mutations."
30241937
OTUB2 deubiquitinates GLI2.
1 | 1
OTUB2 leads to the deubiquitination of GLI2. 2 / 2
1 | 1
ubibrowser
"Here we have identified the eubiquitinating enzyme otubain2 (<span class="match term0">OTUB2</span>) as a regulator of <span class="match term1">Gli2</span> protein degradation"
30241937
reach
"We also found that knockdown of OTUB2 reduced deubiquitination of Gli2 invivo."
30241937
OTUB2 decreases the amount of GLI2.
| 1
OTUB2 decreases the amount of GLI2. 1 / 1
| 1
reach
"Knockdown of OTUB2 decreased Gli2 protein level while the proteasome inhibitor MG-132 treatment restored Gli2 expression."
30241937
OTUB2 affects Neoplasm Metastasis
| 1 15
reach
"Functionally, the overexpression of OTUB2 could promote malignant proliferation and metastasis of HCC cells, while knockdown of OTUB2 exerted the opposite results."
35611163
reach
"Compared to the early passage parental MDA-MB-231 cells, the highly bone-metastatic (BM) derivatives also showed elevated expression of OTUB2 ( Figure 1 C), suggesting OTUB2 could support metastasis."
30472188
reach
"These results support a notion that both DUB activity and SUMO modification of OTUB2 are required to promote lung metastasis in a syngenic mouse tumor model.To further substantiate the function of OTU[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
reach
"As for breast cancer, a recent study reported that OTUB2 deubiquitinated and activated YAP/TAZ to promote cancer stemness and metastasis (Zhang et al., 2019), which confirms the reliability of our results."
36685836
reach
"OTUB2 was identified to enhance breast cancer metastasis."
30472188
reach
"OTUB2 was reported to enhance metastasis through Hippo-independent activation of YAP/TAZ signaling, which could stabilize YAP/TAZ by deubiquitination [37]."
34315490
reach
"Inhibition of OTUB2 promotes apoptosis and attenuates proliferation and metastasis of CC cells by downregulating the AKT/mTOR signalling pathway (Ref."
39377535
reach
"Zhang et al. [12] demonstrated that OTUB2 promoted tumor metastasis by independently activating YAP and TAZ."
39210373
reach
"In addition, OTUB2 promotes breast cancer metastasis by stabilizing Yes-associated protein/WW domain-containing TFs ( Zhang et al., 2019 )."
36288705
reach
"We subsequently examined the role of YAP/TAZ in OTUB2-enhanced cancer stemness and metastasis."
30472188
Ubiquitin affects OTUB2
| 2 9
sparser
"A. thaliana OTU2 and OTLD1 bind UB chains with distinct linkage preferences."
24659992
sparser
"Interestingly, there is a novel oxyanion hole inside OTUB2 generated by the active site loop, which may be conducive to the interaction between OTUB2 and ubiquitin ( xref )."
35309903
sparser
"The deleterious effect of NEM on OTU2 UB chain binding indicates that other Cys residues are likely critical."
24659992
sparser
"Among the eleven A. thaliana OTU DUBs examined, we found that OTU2 and OTLD1 bind UB chains with distinct linkage preferences."
24659992
reach
"Structure of human OTUB2 bound to Ub."
25590432
reach
"Since OTUB2 does not have the N-terminal helix and its alpha1alpha2 loop is 2 residues shorter, it is expected that the binding of proximal Ub to OTUB2 is substantially different from OTUB1."
25590432
sparser
"LotA OTU2 binds to positively charged ubiquitin residues (R42, R72, R74) through the acidic patch (D407, D410, D412) on the EHL."
35651329
sparser
"Although the local resolution was lower due to flexibility (4.0–7.0 Å), we observed a clear density for ubiquitin bound to the Otu2 S1 site (Supplementary Figs.  xref , xref , and xref , xref )."
37169754
sparser
"Like in other Ub-binding proteins and OTU domain containing proteins, Otu2 binds to ubiquitin via a conserved hydrophobic region in the S1 site of the OTU domain (Tyr223, Phe225, Leu255) recognizing a corresponding hydrophobic patch in ubiquitin (Leu8, Ile44, Val70), as described before for various types of ubiquitin-binding proteins including the OTU family of DUBs xref , xref , xref – xref (Fig.  xref )."
37169754
sparser
"Structure of human OTUB2 bound to Ub."
25590432
OTUB2 affects TRAF3
1 1 | 1 10 1
OTUB2 deubiquitinates TRAF3.
1 | 7
OTUB2 deubiquitinates TRAF3. 8 / 8
1 | 7
reach
"OTUB1 and OTUB2, which are members of the OTUB deubiquitinase superfamily, may deubiquitinate TRAF3 and TRAF6, stop SeV-induced NF-κB and IRF3 activation, and aid in viral replication [41] ."
37001379
reach
"OTUB1 and its paralog OTUB2, deubiquitinate TRAF3 and TRAF6 to inhibit virus triggered signaling pathways that ultimately result in IRF3 and NF-kappaB activation [XREF_BIBR]."
23845989
reach
"OTUB1 and OTUB2 interact with and deubiquitinate TRAF3 and TRAF6, which are required for virus triggered IRF3 and NF-kappaB activation [XREF_BIBR]."
23151130
reach
"Furthermore, we found that OTUB1 and OTUB2 mediated virus triggered deubiquitination of TRAF3 and -6."
19996094
reach
"OTUB1 and OTUB2 regulate virus-triggered IFN inflammation by deubiquitinating TRAF3 and TRAF6 [75]."
32650621
ubibrowser
"Regulation of virus-triggered signaling by OTUB1- and <span class="match term0">OTUB2</span>-mediated deubiquitination of <span class="match term1">TRAF3</span> and TRAF6"
19996094
reach
"Two close relatives of DUBA, OTUB1 and OTUB2, were shown to reduce TRAF3 ubiquitination coupled with decreased anti-viral signaling responses in Sendai virus infected HEK 293T cells."
22017431
reach
"It was also shown that two OTUB deubiquitinating enzyme family members, OTUB1 and OTUB2, can deubiquitinate TRAF3 and TRAF6, leading to the inhibition of virus induced IFN-beta expression and cellular antiviral responses."
28717359
OTUB2 binds TRAF3.
1 | 2 1
OTUB2 binds TRAF3. 3 / 3
1 | 2
reach
"OTUB1 and OTUB2 interact with and deubiquitinate TRAF3 and TRAF6, which are required for virus triggered IRF3 and NF-kappaB activation [XREF_BIBR]."
23151130
biogrid
No evidence text available
19996094
reach
"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63 linked polyubiquitin chains."
33511009
OTUB1 binds OTUB2, TRAF3, and TRAF6. 1 / 1
| 1
sparser
"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63‐linked polyubiquitin chains. [ xref ] Because various components are involved in virus‐induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG‐I‐, MDA5‐, and MAVS‐mediated but not TBK1‐ and IRF3‐mediated signaling."
33511009
OTUB2 inhibits TRAF3.
| 1 1
OTUB2 inhibits TRAF3. 2 / 2
| 1 1
reach
"TRAF3 and TRAF6 are both deactivated by the DUbs otubain 1 (OTUB1) and OTUB2, which remove K63 linked polyubiquitin chains."
26712804
eidos
"TRAF3 and TRAF6 are both deactivated by the DUbs otubain 1 ( OTUB1 ) and OTUB2 , which remove K63-linked polyubiquitin chains ( Li et al ., 2010b ) ."
26712804
OTUB2 affects STAT1
| 11 3
OTUB2 deubiquitinates STAT1.
| 5
OTUB2 deubiquitinates STAT1. 5 / 5
| 5
reach
"In addition, OTUB2 deubiquitinates STAT1 to promote its phosphorylation and dimerization ."
40307212
reach
"Mechanistically, OTUB2 mediates the deubiquitination and phosphorylation of STAT1 and further promotes calmodulin-like protein 3 (CALML3) upregulation."
38989149
reach
"In contrast, Chang et al. [56] discovered that OTUB2 is missing in ESCC tissues, while OTUB2 can deubiquitinate STAT1 and phosphorylate it, thereby activating CALML3 transcription and phospholipid acetylserine synthesis to exert tumor suppressive effects."
38819228
reach
"Previous IB results indicated that OTUB2 did not affect total STAT1 protein levels ( Figures 4 D and 4E), suggesting that deubiquitination of STAT1 by OTUB2 is atypical, regardless of protein stabilit[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36288705
reach
"These results supported our conclusion that K173 and K637 are essential lysine sites that facilitate the deubiquitination of STAT1 by OTUB2 and the subsequent regulation of STAT1 dimerization and tran[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36288705
OTUB2 phosphorylates STAT1.
| 3 1
OTUB2 leads to the phosphorylation of STAT1. 3 / 3
| 2 1
reach
"Mechanistically, OTUB2 mediates the deubiquitination and phosphorylation of STAT1 and further promotes calmodulin-like protein 3 (CALML3) upregulation."
38989149
reach
"To further elucidate the regulatory mechanism underlying STAT1 phosphorylation by OTUB2, PLAs with antibodies against JAKs were performed in SCC cells; the results indicated that OTUB2 promoted the as[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36288705
sparser
"To further elucidate the regulatory mechanism underlying STAT1 phosphorylation by OTUB2, PLAs with antibodies against JAKs were performed in SCC cells; the results indicated that OTUB2 promoted the as[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36288705
OTUB2 leads to the phosphorylation of STAT1 on Y701. 1 / 1
| 1
reach
"Moreover, OTUB2 promotes the interaction between STAT1 and JAKs, increases STAT1 phosphorylation at Tyr701, and augments the transcriptional activity of STAT1 to activate CALML3 expression."
36288705
OTUB2 binds STAT1.
| 2 2
OTUB2 binds STAT1. 4 / 4
| 2 2
reach
"Mechanistically, OTUB2 cleaves K6- and K63-associated ubiquitin linkages on signal transducer and activator of transcription 1 (STAT1), resulting in enhanced phosphorylation at Tyr701, dimerization, a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36288705
sparser
"The above results indicated that the interaction between OTUB2 and STAT1 is dependent on the enzymatic activity of OTUB2."
36288705
reach
"The above results indicated that the interaction between OTUB2 and STAT1 is dependent on the enzymatic activity of OTUB2."
36288705
sparser
"We found that OTUB2 specifically interacts with STAT1 and primarily cleaves K6- and K63-linked ubiquitin chains on STAT1."
36288705
OTUB2 dephosphorylates STAT1.
| 1
OTUB2 leads to the dephosphorylation of STAT1 on Y701. 1 / 1
| 1
reach
"By contrast, OTUB2 knockdown in the two SCC cell lines significantly reduced STAT1 Tyr701 phosphorylation ( Figure 4 E)."
36288705
OTUB2 affects MYC
1 | 3 10
OTUB2 binds MYC.
1 | 10
OTUB2 binds MYC. 10 / 11
1 | 10
sparser
"The same conclusions were obtained from a proximity ligation assay (PLA) in ES-2 and A2780 cells stably expressing Myc-OTUB2 and Flag-SNX29P2 ( xref )."
38701117
sparser
"RD21A‐FLAG exhibited increased accumulation when co‐expressed with OTU2‐Myc compared to the control (Figure  xref )."
40223806
sparser
"To further elucidate the role of OTU2 in stabilizing RD21A, we co‐expressed RD21A‐FLAG with OTU2‐Myc or an empty vector in N. benthamiana leaves."
40223806
biogrid
No evidence text available
35217790
sparser
"Notably, the presence of OTU2‐Myc suppressed the co‐precipitation of RD21A‐FLAG with PbE3‐2‐GFP, suggesting that OTU2 interferes with the interaction between PbE3‐2 and RD21A in plants (Figure  xref )."
40223806
sparser
"Given that OTU2 is a DUB, we hypothesized that it may remove ubiquitin modifications from RD21A. To test this, Ub‐HA, PbE3‐2‐GFP and RD21A‐FLAG were co‐expressed with either OTU2‐Myc or Ev‐Myc in N. benthamiana leaves."
40223806
sparser
"Transient expression of PbE3‐2‐GFP, RD21A‐FLAG and OTU2‐Myc in N. benthamiana revealed that OTU2 increased RD21A accumulation compared to the control with an empty vector (Figure  xref ), suggesting that OTU2 may protect RD21A from degradation mediated by PbE3‐2."
40223806
sparser
"Similarly, mRD21A also showed enhanced protein accumulation in the presence of OTU2‐Myc (Figure  xref )."
40223806
sparser
"To validate the existence of TFs that mediate the activation of CALML3 by OTUB2, immunoprecipitation (IP) experiments in KYSE30 and UM1 cells expressing Myc-OTUB2 proteins were performed using anti-My[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36288705
sparser
"Since our previous data indicated that the tumor-suppressive role of OTUB2 relies on its enzymatic activity, an IP group using cells expressing Myc-OTUB2 C51S was included to exclude proteins whose in[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36288705
OTUB2 activates MYC.
| 2
OTUB2 activates MYC. 2 / 2
| 2
reach
"Collectively, these data indicate that OTUB2 promotes the Warburg effect by modulating HIF1a and c-Myc."
30662561
reach
"OTUB2 may stimulate the Warburg effect by regulating HIF1a and c-Myc in NSCLC cells."
30662561
OTUB2 increases the amount of MYC.
| 1
OTUB2 increases the amount of MYC. 1 / 1
| 1
reach
"Moreover, it was very intriguing for us to show that OTUB2 promoted the protein expression of HIF1a and c-Myc and induced activation of the AKT and mTOR pathway."
30662561
OTUB2 affects CTNNB1
1 | 1 9 2
OTUB2 activates CTNNB1.
| 1 4
OTUB2 activates CTNNB1. 5 / 5
| 1 4
reach
"These results indicated that OTUB2-regulated expression of CTNNB1 could enhance ZEB1 to promote the invasion and metastasis of iCCA cells.To further investigate the mechanism of CTNNB1 upregulation in[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36858343
reach
"We performed further experiments with the autophagy inhibitor 3-MA, lysosomal inhibitor NH4Cl, and proteasome inhibitor MG132 and found that the autophagy inhibitor and lysosomal inhibitor restored ac[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36858343
reach
"Additionally, Xu et al. also demonstrated that OTUB2 promotes colorectal cancer growth by regulating β-catenin signaling [38]."
40296903
reach
"showed that inhibiting OTUB2 can suppress the growth of colorectal cancer cells by modulating the β-catenin signaling pathway."
39210373
eidos
"Mechanistically , OTUB2 promotes CTNNB1 expression by interacting with the E3 ligase TRAF6 ."
36858343
OTUB2 binds CTNNB1.
1 | 1 2
OTUB2 binds CTNNB1. 4 / 4
1 | 1 2
biogrid
No evidence text available
30323974
sparser
"We then performed reciprocal co-immunoprecipitations and demonstrated that OTUB2 and β-Catenin bound to each other."
38058843
reach
"The direct binding of OTUB2 to CTNNB1 in iCCA cells was verified by a Co-IP assay, and overexpression of CTNNB1 in cells with OTUB2 knockdown could rescue ZEB1 expression."
36858343
sparser
"The direct binding of OTUB2 to CTNNB1 in iCCA cells was verified by a Co-IP assay, and overexpression of CTNNB1 in cells with OTUB2 knockdown could rescue ZEB1 expression."
36858343
OTUB2 inhibits CTNNB1.
| 3
OTUB2 inhibits CTNNB1. 3 / 3
| 3
reach
"Further confocal immunofluorescence assay results confirmed that OTUB2 loss promoted CTNNB1 enrichment in lysosomal compartments ( Fig. 6 D)."
36858343
reach
"The Co-IP data revealed that the depletion of OTUB2 increased CTNNB1 occupancy on the ZEB1 promoter ( Fig. 5 B)."
36858343
reach
"Silencing OTUB2 induced decreases in ZEB1 and CTNNB1, and CTNNB1 overexpression markedly reversed the change in ZEB1 expression ( Fig. 5 D)."
36858343
OTUB2 increases the amount of CTNNB1.
| 1
OTUB2 increases the amount of CTNNB1. 1 / 1
| 1
reach
"Correspondingly, knockdown of OTUB2 in QBC939 and RBC cells significantly decreased CTNNB1 expression ( Fig. 5 C)."
36858343
TRAF6 affects OTUB2
3 | 5 4
OTUB2 binds TRAF6. 10 / 11
3 | 5 3
sparser
"This analysis revealed a potential interaction between OTUB2 and TRAF6 ( xref ), and subsequent studies confirmed that TRAF6 is a substrate of OTUB2."
40296903
biogrid
No evidence text available
19996094
sparser
"These results demonstrated that TRAF6 binding to OTUB2 is crucial for its induction of autophagy and selective autophagic CTNNB1 degradation."
36858343
reach
"OTUB1 and OTUB2 interact with and deubiquitinate TRAF3 and TRAF6, which are required for virus triggered IRF3 and NF-kappaB activation [XREF_BIBR]."
23151130
reach
"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63 linked polyubiquitin chains."
33511009
sparser
"More than this special feature, if OTUB2 interacts with TRAF6, the result should benefit the NF-kappaB pathway."
35309903
biogrid
No evidence text available
23105109
reach
"This analysis revealed a potential interaction between OTUB2 and TRAF6 (Fig. 5A), and subsequent studies confirmed that TRAF6 is a substrate of OTUB2."
40296903
reach
"Therewith, we demonstrated the exogenous binding between OTUB2 and TRAF6 in HEK293T cells by Co-immunoprecipitation (Co-IP) assays (Fig. 5B)."
40296903
reach
"These results demonstrated that TRAF6 binding to OTUB2 is crucial for its induction of autophagy and selective autophagic CTNNB1 degradation."
36858343
OTUB1 binds OTUB2, TRAF3, and TRAF6. 1 / 1
| 1
sparser
"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63‐linked polyubiquitin chains. [ xref ] Because various components are involved in virus‐induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG‐I‐, MDA5‐, and MAVS‐mediated but not TBK1‐ and IRF3‐mediated signaling."
33511009
GLI2 affects OTUB2
3 | 1 8
OTUB2 binds GLI2. 10 / 12
3 | 1 8
biogrid
No evidence text available
30241937
biogrid
No evidence text available
30241937
biogrid
No evidence text available
30241937
sparser
"We provided evidence that OTUB2 binds to and deubiquitinates Gli2, playing a critical role in regulating the Hh signaling pathway."
30241937
sparser
"The authors found that OTUB2 formed a complex with Gli2 and promoted Gli2 deubiquitination both in vitro and in vivo."
| PMC
sparser
"Furthermore, we confirmed that OTUB2 could bind to Gli2, which indicated that Gli2 were substrates for OTUB2."
30241937
sparser
"To identify the interactions between endogenous Gli2 and OTUB2, HEK293A cells were transfected with Flag-tagged OTUB2 construct or vector control, and the cell lysate was subjected to immunoprecipitat[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30241937
sparser
"To identify the interactions between endogenous OTUB2 and Gli2, HEK293A cells were transfected with Flag-tagged Gli2, then the cell lysate was subjected to IP using anti-Flag magnetic beads (M8823, Si[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30241937
reach
"The authors found that OTUB2 formed a complex with Gli2 and promoted Gli2 deubiquitination both in vitro and in vivo."
| PMC
sparser
"Meanwhile, the interaction between OTUB2 and Gli2 was determined by immunoprecipitation ( xref )."
35309903
OTUB2 affects necroptotic process
| 11
reach
"Given that RIPK3 critically regulates necroptosis and that OTUB2 increases RIPK3 abundance and activity, we then assessed whether OTUB2 enhanced neuronal necroptosis via regulating RIPK3."
40021931
reach
"Besides, OTUB2 deficiency significantly reduced the levels of phosphorylated RIPK3 and MLKL in primary neurons after OGD (Fig. 6C–F), showing that OTUB2 increases neuronal necroptosis after ischemia."
40021931
reach
"Next, we specifically induced necroptosis with a cocktail of TNF-α, CHX, and Z-VAD-FMK (TCZ) and found that Otub2 cells died significantly less than Otub2 cells (Fig. 6G; Appendix Fig. S11D), unambiguously demonstrating that OTUB2 deletion diminishes necroptosis."
40021931
reach
"Treatment with the RIPK3 inhibitor GSK-872 or the MLKL inhibitor GW806742X restored the viability of Otub2 cells and erased the difference between the two genotypes after TCZ stimulation (Fig. 6G; Appendix Fig. S11E), indicating that OTUB2 promotes necroptosis by regulating the RIPK3-MLKL signaling."
40021931
reach
"Moreover, overexpression of OTUB2 increased necroptosis whereas overexpression of the OTUB2 C51S mutant exerted no effect (Fig. 6H)."
40021931
reach
"Collectively, these findings show that OTUB2 enhances ischemia-induced neuronal necroptosis by regulating RIPK3 through its DUB activity."
40021931
reach
"OTUB2 potentiates neuronal necroptosis after ischemia."
40021931
reach
"These in vitro and in vivo data synergistically demonstrate that OTUB2 enhances ischemic stroke injury by potentiating neuronal necroptosis through RIPK3.Since OTUB2 promoted neuronal necroptosis and genetic deletion of OTUB2 ameliorated ischemic stroke injury, we further investigated whether inhibition of OTUB2 with inhibitors could protect mice from ischemic stroke."
40021931
reach
"In good agreement with the Western blot results, MLKL phosphorylation was significantly reduced in neurons of Otub2 mice after MCAO (Fig. 3H,I), showing that OTUB2 deficiency attenuates neuronal necroptosis."
40021931
reach
"To directly confirm that OTUB2 enhances neuronal necroptosis after the ischemic insult, Otub2 and Otub2 HT22 cells were subjected to oxygen-glucose deprivation (OGD)."
40021931
OTUB2 affects L3MBTL1
1 | 10
OTUB2 deubiquitinates L3MBTL1.
1 | 6
OTUB2 deubiquitinates L3MBTL1. 7 / 7
1 | 6
reach
"However, OTUB2 deubiquitinates L3MBTL1 and suppresses the RNF8 mediated ubiquitination of L3MBTL1, which leads to less recruitment of RAP80 and 53BP1 to DSBs and therefore increases HR."
30831436
reach
"In addition, DSB induced L3MBTL1 ubiquitination (Acs et al., 2011) was also antagonized by OTUB2 in a DUB activity dependent manner."
24560272
reach
"Finally, we investigated whether OTUB2 could deubiquitinate L3MBTL1 in vitro."
24560272
reach
"Thus, OTUB2 deubiquitinates L3MBTL1 in vivo and in vitro."
24560272
reach
"Because ubiquitination of L3MBTL1 is a prerequisite for L3MBTL1 removal from damaged chromatin (Acs et al., 2011), we conclude that OTUB2 deubiquitinates L3MBTL1 and suppresses the accelerated removal[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24560272
ubibrowser
"Mechanistically, <span class="match term0">OTUB2</span> suppresses RNF8-mediated <span class="match term1">L3MBTL1</span> ubiquitination and Lys 63-linked ubiquitin chain formation in a deubiquitinating activity-dependent manner."
24560272
reach
"These data suggest that the interaction between OTUB2 and L3MBTL1 is constitutive rather than DNA damage dependent.Next, we investigated whether OTUB2 could deubiquitinate L3MBTL1 in vivo."
24560272
OTUB2 binds L3MBTL1.
| 2
OTUB2 binds L3MBTL1. 2 / 2
| 2
reach
"Therefore, we focused on L3MBTL1 and asked whether OTUB2 prevented RNF8 mediated ubiquitination of L3MBTL1.First, to confirm whether OTUB2 interacts with L3MBTL1, we performed a coimmunoprecipitation [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24560272
reach
"These data suggest that the interaction between OTUB2 and L3MBTL1 is constitutive rather than DNA damage dependent.Next, we investigated whether OTUB2 could deubiquitinate L3MBTL1 in vivo."
24560272
OTUB2 ubiquitinates L3MBTL1.
| 1
OTUB2 leads to the ubiquitination of L3MBTL1. 1 / 1
| 1
reach
"A slight increment in OTUB2 at sites of DSB, which can be detected only by micro-laser irradiation, probably elevates overall DUB activity of OTUB2 to respond the DSB induced ubiquitination of L3MBTL1[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24560272
OTUB2 decreases the amount of L3MBTL1.
| 1
OTUB2 decreases the amount of ubiquitinated L3MBTL1. 1 / 1
| 1
reach
"When in vivo ubiquitinated L3MBTL1 was incubated with recombinant OTUB2 proteins, recombinant OTUB2 decreased the amount of ubiquitinated L3MBTL1 and generated ubiquitin monomers."
24560272
MYC affects OTUB2
1 | 10
OTUB2 binds MYC. 10 / 11
1 | 10
sparser
"The same conclusions were obtained from a proximity ligation assay (PLA) in ES-2 and A2780 cells stably expressing Myc-OTUB2 and Flag-SNX29P2 ( xref )."
38701117
sparser
"RD21A‐FLAG exhibited increased accumulation when co‐expressed with OTU2‐Myc compared to the control (Figure  xref )."
40223806
sparser
"To further elucidate the role of OTU2 in stabilizing RD21A, we co‐expressed RD21A‐FLAG with OTU2‐Myc or an empty vector in N. benthamiana leaves."
40223806
biogrid
No evidence text available
35217790
sparser
"Notably, the presence of OTU2‐Myc suppressed the co‐precipitation of RD21A‐FLAG with PbE3‐2‐GFP, suggesting that OTU2 interferes with the interaction between PbE3‐2 and RD21A in plants (Figure  xref )."
40223806
sparser
"Given that OTU2 is a DUB, we hypothesized that it may remove ubiquitin modifications from RD21A. To test this, Ub‐HA, PbE3‐2‐GFP and RD21A‐FLAG were co‐expressed with either OTU2‐Myc or Ev‐Myc in N. benthamiana leaves."
40223806
sparser
"Transient expression of PbE3‐2‐GFP, RD21A‐FLAG and OTU2‐Myc in N. benthamiana revealed that OTU2 increased RD21A accumulation compared to the control with an empty vector (Figure  xref ), suggesting that OTU2 may protect RD21A from degradation mediated by PbE3‐2."
40223806
sparser
"Similarly, mRD21A also showed enhanced protein accumulation in the presence of OTU2‐Myc (Figure  xref )."
40223806
sparser
"To validate the existence of TFs that mediate the activation of CALML3 by OTUB2, immunoprecipitation (IP) experiments in KYSE30 and UM1 cells expressing Myc-OTUB2 proteins were performed using anti-My[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36288705
sparser
"Since our previous data indicated that the tumor-suppressive role of OTUB2 relies on its enzymatic activity, an IP group using cells expressing Myc-OTUB2 C51S was included to exclude proteins whose in[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36288705
OTUB2 affects PKM2
| 6 4
OTUB2 binds PKM2.
| 4
OTUB2 binds PKM2. 4 / 4
| 4
sparser
"OTUB2 directly interacts with PKM2 to inhibit its ubiquitination by disrupting the interaction between PKM2 and E3 ubiquitin ligase Parkin, thus enhancing its pyruvate kinase activity and promoting the Warburg effect [ xref ]."
40137167
sparser
"OTUB2, an OTU deubiquitinase, directly interacts with PKM2 and suppresses its ubiquitination via weakening the interaction of PKM2 and Parkin to increase PKM2 activity and glycolysis in colorectal cancer ( xref )."
38910890
sparser
"In colon cancer, OTUB2 interacts with PKM2, enhancing its activity and promoting glycolysis, thereby facilitating colorectal cancer progression [ xref ]."
39380010
sparser
"Moreover, the deubiquitinase OTUB2 directly interacts with PKM2 and inhibits its ubiquitination, resulting in enhanced glycolysis, proliferation and migratory capacity in CRC cells [ xref ]."
39993964
OTUB2 deubiquitinates PKM2.
| 3
OTUB2 leads to the deubiquitination of PKM2. 3 / 3
| 3
reach
"For example, OTUB2 negatively regulates PKM2 ubiquitination and the depletion of OTUB2 reduces the glucose consumption, lactate production and cellular ATP production, exhibiting attenuated proliferation and migration and increased sensitivity to chemotherapy drugs for CRC [18]."
35546050
reach
"Yu et al. showed that OTUB2, a deubiquitinating enzyme, inhibited the ubiquitination of PKM2 by competitively binding to it with Parkin (ubiquitin E3 ligase), which enhanced the activity of PKM2 and promoted glycolysis, promoting the development of colon cancer [26]."
40011864
reach
"For example, OTUB2 inhibits PKM2 ubiquitination and enhances its activity in colorectal cancer [42]."
37624791
OTUB2 ubiquitinates PKM2.
| 1
OTUB2 leads to the ubiquitination of PKM2. 1 / 1
| 1
reach
"Meanwhile, OTUB2 is upregulated in CRC and blocks the interaction between pyruvate kinase 2 (PKM2) and ubiquitin ligase E3, which inhibits PKM2 ubiquitination and degradation."
38485957
OTUB2 increases the amount of PKM2.
| 1
OTUB2 increases the amount of PKM2. 1 / 1
| 1
reach
"In addition, the silencing of OTUB2 significantly suppressed the expression levels of PKM2."
36316812
OTUB2 activates PKM2.
| 1
OTUB2 activates PKM2. 1 / 1
| 1
reach
"In colon cancer, Yu et al. [14] demonstrated that OTUB2 promotes the malignant progression of colorectal cancer by enhancing PKM2 activity and glycolysis."
39210373
OTUB2 affects OTUB1
| 10
OTUB1 binds OTUB2. 9 / 9
| 9
sparser
"The result showed that Flag-GD-NT interacted with both OTUB1 and OTUB2 (Fig. xref )."
40097387
sparser
"On the other hand, OTU1-OTU3 comparisons showed four total upregulated and 88 downregulated genes in OTU1-dominated communities, whereas OTU1-OTU2 comparisons showed 751 total upregulated and 403 downregulated genes in OTU1-dominated communities ( xref )."
31455638
sparser
"Binding of Known Covalent SARS-CoV PLpro Inhibitors to OTUB2/OTUB1/SARS-CoV-2 PLpro."
34071582
sparser
"A coimmunoprecipitation (co-IP) assay using mutant PD-L1 or OTUB2 proteins with different structural domains deleted revealed the involvement of the ICD (261–290) of PD-L1 in the interaction with OTUB2 and the OTU domain (44–234) of OTUB2 in the interaction with PD-L1 (Fig.  xref )."
38167274
sparser
"Next, Kaplan-Meier's survival analysis was performed to examine the expression of five deubiquitinating enzymes in 117 NSCLC patients (GEO Submission: GSE13213) and revealed that the higher expression of OTUB1 and OTUB2 was significantly associated with poor patient prognosis (Figure xref B-EandFigure xref E)."
30662561
sparser
"OTUB1 and OTUB2 interact with and deubiquitinate TRAF3 and TRAF6, which are required for virus-triggered IRF3 and NF-κB activation [ xref ]."
23151130
sparser
"Since local resolution of the OTU domain was not sufficient to build a de novo molecular model, we determined the structure of the N-terminally extended Otu2-OTU domain comprising residues 150–307 by X-ray crystallography (Supplementary Table  xref and Supplementary Fig.  xref )."
37169754
sparser
"OTU1 and OTU2 ( R. radiotolerans ) associated to the meteorites ( p = 0.034), as did OTU5 ( Blastococcus sp.) p = 0.034, OTU6 ( G. pulveris ) p = 0.034, OTU12 (Chloroflexi) p = 0.028, OTU15 ( B. jejuensis ) p = 0.034, OTU19 (Frankiales) p = 0.034, OTU21 ( D. navajonensis ) p = 0.034, and OTU23 ( Rubrobacter sp.) p = 0.032."
28713354
sparser
"Therefore, we hypothesized that the cryo-EM electron density map presented the different orientation of OTU1-OTU2 domains with respect to each other and perhaps the domain orientation is variable in solution."
37100438
OTUB1 binds OTUB2, TRAF3, and TRAF6. 1 / 1
| 1
sparser
"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63‐linked polyubiquitin chains. [ xref ] Because various components are involved in virus‐induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG‐I‐, MDA5‐, and MAVS‐mediated but not TBK1‐ and IRF3‐mediated signaling."
33511009
OTUB2 affects Neoplasms
| 10
OTUB2 activates Neoplasms. 10 / 10
| 10
reach
"When cultured in suspension, OTUB2 deficiency sharply reduced the number of tumor-like mammospheres, whereas ectopic expression of OTUB2-wild-type (OTUBS-WT), but not of the CS mutant, greatly enhance[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
reach
"Statistical analysis confirmed that loss of OTUB2 decreased the frequency of tumor-initiating cells ( Table S3 )."
30472188
reach
"Zhang et al. [12] demonstrated that OTUB2 promoted tumor metastasis by independently activating YAP and TAZ."
39210373
reach
"These results suggest that when the expression of OTUB2 in ESCC cell line KYSE150 was down regulated, the proliferation, migration and invasion of KYSE150 cells is inhibited, which further indicates that OTUB2 knockdown can inhibit the growth and progression of tumor."
35850645
reach
"These authors found that OTUB2 could directly act on YAP1/TAZ independently of the Hippo signaling pathway to promote tumor proliferation."
35850645
reach
"OTUB2 promotes TNBC cell proliferation in vitro and tumor growth."
40296903
reach
"The subcutaneous xenograft model showed that OTUB2 knockdown suppressed tumor growth in vivo (Fig. 3E–G)."
40296903
reach
"In ESCC, DNA hypermethylation of otubain 2 (OTUB2) has been found to induce tumor initiation and chemoresistance by regulating biosynthesis of phosphatidylserine."
38989149
reach
"Furthermore, in vivo assays show that knockout of OTUB2 inhibits tumor growth in mice."
34671086
reach
"OTUB2-WT expression increased spontaneous lung metastasis without affecting primary tumor growth, whereas expression of OTUB2-CS or OTUB2-KR had no significant effects ( Figure 5 E–5H)."
30472188
OTUB1 affects OTUB2
| 10
OTUB1 binds OTUB2. 9 / 9
| 9
sparser
"The result showed that Flag-GD-NT interacted with both OTUB1 and OTUB2 (Fig. xref )."
40097387
sparser
"On the other hand, OTU1-OTU3 comparisons showed four total upregulated and 88 downregulated genes in OTU1-dominated communities, whereas OTU1-OTU2 comparisons showed 751 total upregulated and 403 downregulated genes in OTU1-dominated communities ( xref )."
31455638
sparser
"Binding of Known Covalent SARS-CoV PLpro Inhibitors to OTUB2/OTUB1/SARS-CoV-2 PLpro."
34071582
sparser
"A coimmunoprecipitation (co-IP) assay using mutant PD-L1 or OTUB2 proteins with different structural domains deleted revealed the involvement of the ICD (261–290) of PD-L1 in the interaction with OTUB2 and the OTU domain (44–234) of OTUB2 in the interaction with PD-L1 (Fig.  xref )."
38167274
sparser
"Next, Kaplan-Meier's survival analysis was performed to examine the expression of five deubiquitinating enzymes in 117 NSCLC patients (GEO Submission: GSE13213) and revealed that the higher expression of OTUB1 and OTUB2 was significantly associated with poor patient prognosis (Figure xref B-EandFigure xref E)."
30662561
sparser
"OTUB1 and OTUB2 interact with and deubiquitinate TRAF3 and TRAF6, which are required for virus-triggered IRF3 and NF-κB activation [ xref ]."
23151130
sparser
"Since local resolution of the OTU domain was not sufficient to build a de novo molecular model, we determined the structure of the N-terminally extended Otu2-OTU domain comprising residues 150–307 by X-ray crystallography (Supplementary Table  xref and Supplementary Fig.  xref )."
37169754
sparser
"OTU1 and OTU2 ( R. radiotolerans ) associated to the meteorites ( p = 0.034), as did OTU5 ( Blastococcus sp.) p = 0.034, OTU6 ( G. pulveris ) p = 0.034, OTU12 (Chloroflexi) p = 0.028, OTU15 ( B. jejuensis ) p = 0.034, OTU19 (Frankiales) p = 0.034, OTU21 ( D. navajonensis ) p = 0.034, and OTU23 ( Rubrobacter sp.) p = 0.032."
28713354
sparser
"Therefore, we hypothesized that the cryo-EM electron density map presented the different orientation of OTU1-OTU2 domains with respect to each other and perhaps the domain orientation is variable in solution."
37100438
OTUB1 binds OTUB2, TRAF3, and TRAF6. 1 / 1
| 1
sparser
"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63‐linked polyubiquitin chains. [ xref ] Because various components are involved in virus‐induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG‐I‐, MDA5‐, and MAVS‐mediated but not TBK1‐ and IRF3‐mediated signaling."
33511009
EGF affects OTUB2
| 6 4
EGF sumoylates OTUB2. 10 / 10
| 6 4
reach
"Thus, these clinical data support our model that EGF signaling or RAS activation stimulates OTUB2 SUMOylation and thereby stabilizes YAP/TAZ, which enhances cancer stemness and metastasis ( Figure 7 K[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
reach
"Moreover, we found that EGF, which can activate RAS, also promotes OTUB2 SUMOylation."
30472188
sparser
"Moreover, OTUB2 poly-SUMOylation was stimulated by epidermal growth factor (EGF) and oncogenic KRAS mutation."
30472188
sparser
"Importantly, EGF and oncogenic KRAS induce OTUB2 poly-SUMOylation and thereby activate YAP/TAZ."
36264492
reach
"Moreover, OTUB2 poly-SUMOylation was stimulated by epidermal growth factor (EGF) and oncogenic KRAS mutation."
30472188
sparser
"Furthermore, OTUB2 sumoylation is stimulated by EGF and oncogenic KRAS, which is essential for EGF and KRAS to stabilize Yap/Taz ( xref )."
33869224
reach
"Therefore, our observations suggest that EGF and RAS activation might be able to regulate YAP/TAZ through SUMOylating OTUB2."
30472188
reach
"Interestingly, the SUMOylation of OTUB2 is induced by EGF and KRAS [78]."
38136274
reach
"Poly-SUMOylated OTUB2, which was induced by Epidermal growth factor (EGF) and oncogenic KRAS, was shown to bind and activate YAP/TAZ promoting tumor metastasis [68]."
31619007
sparser
"Interestingly, the SUMOylation of OTUB2 is induced by EGF and KRAS [ xref ]."
38136274
RD21A affects OTUB2
| 2 7
OTUB2 binds RD21A. 7 / 7
| 7
sparser
"To investigate this, we performed a yeast two‐hybrid (Y2H) assay, which confirmed that OTU2 interacts with RD21A but not with PbE3‐2 (Figure  xref ; Figure  xref )."
40223806
sparser
"Consistent with these results, Split‐LUC assays demonstrated that OTU2 interacts with full‐length RD21A (RD21A), intermediate RD21A (iRD21A) and mature RD21A (mRD21A) (Figure  xref )."
40223806
sparser
"To further validate the OTU2–RD21A interaction, we performed a co‐immunoprecipitation (Co‐IP) assay."
40223806
sparser
"Additionally, BiFC assays demonstrated that OTU2 interacts with RD21A in both the cytoplasm and the cell membrane (Figure  xref ; Figure  xref )."
40223806
sparser
"Together, these results confirm that OTU2 interacts with RD21A, highlighting its potential role in counteracting the PbE3‐2‐mediated degradation of RD21A."
40223806
sparser
"To investigate the structural requirements for the interaction between OTU2 and RD21A, we used truncated derivatives of OTU2 in Y2H assays."
40223806
sparser
"We found that RD21A interacts with OTUc (124–208 aa) but not with OTUn (11–123 aa), indicating that the C2H2 zinc finger domain is essential for the interaction between OTU2 and RD21A (Figure  xref )."
40223806
OTUB2 binds RD21A. 2 / 2
| 2
reach
"To investigate the structural requirements for the interaction between OTU2 and RD21A, we used truncated derivatives of OTU2 in Y2H assays."
40223806
reach
"We found that RD21A interacts with OTUc (124–208 aa) but not with OTUn (11–123 aa), indicating that the C2H2 zinc finger domain is essential for the interaction between OTU2 and RD21A (Figure S2c)."
40223806
OTUB2 activates oxidative phosphorylation. 7 / 7
| 7
reach
"Having demonstrated that OTUB2/SNX29P2 causes impaired glycolysis and increased OXPHOS in ovarian cancer cells, we then identified the mediator of this function."
38701117
reach
"Overexpression of CA9 abolished the decreases in glycolysis and lactate production and the increase in OXPHOS caused by overexpression of OTUB2 and SNX29P2 (SI Appendix, Fig. S5 G–K)."
38701117
reach
"OTUB2/SNX29P2 Suppresses Glycolysis and Promotes OXPHOS in Ovarian Cancer.."
38701117
reach
"The results of gene set enrichment analysis (GSEA) indicated that overexpression of either OTUB2 or SNX29P2 suppresses the glycolysis pathway and enhances OXPHOS activity (Fig. 4 A and B)."
38701117
reach
"Overexpression of either OTUB2 or CALML3 in KYSE30 cells enhanced OXPHOS, as demonstrated by elevated basal respiration, maximal respiration, and ATP production ( Figures 3 I and 3J)."
36288705
reach
"The results indicated that silencing OTUB2 significantly increased glycolytic capacity and lactate production and inhibited OXPHOS (Fig. 4 F–H and SI Appendix, Fig. S4 E and F)."
38701117
reach
"Furthermore, the increased glycolysis and decreased OXPHOS mediated by OTUB2 silencing could be effectively reversed by the expression of shRNA-resistant wild-type OTUB2 (SI Appendix, Fig. S4 G–L)."
38701117
reach
"We showed that OTUB2 prevents cancer stemness via elevated OXPHOS and subsequently increased PS synthesis."
36288705
reach
"Furthermore, the increased glycolysis and decreased OXPHOS mediated by OTUB2 silencing could be effectively reversed by the expression of shRNA-resistant wild-type OTUB2 (SI Appendix, Fig. S4 G–L)."
38701117
OTUB2 affects SP1
1 | 5 3
OTUB2 binds SP1.
1 | 2 3
SP1 binds OTUB2. 6 / 6
1 | 2 3
sparser
"Additionally, the results from endogenous and exogenous co-immunoprecipitation (CO-IP) experiments further supported the interaction between OTUB2 protein and SP1 protein (Fig.  xref C, D)."
39210373
reach
"Confocal microscopy results also revealed the binding between OTUB2 and SP1 in colon cancer cells (Fig. 5B)."
39210373
reach
"Second, while we have demonstrated that OTUB2 can inhibit K48 ubiquitination-mediated degradation of SP1 and upregulate its expression, it remains unknown whether OTUB2 competitively binds to the ubiquitin or E3 ubiquitin ligase binding site on SP1."
39210373
sparser
"OTUB2 interacted with SP1 to suppress its K48 ubiquitination, thereby upregulating its protein expression level."
39210373
sparser
"First, although we have shown that SP1 is a target protein of OTUB2, we have not further identified the specific structural domain or binding site where OTUB2 interacts with SP1."
39210373
biogrid
No evidence text available
35140242
OTUB2 increases the amount of SP1.
| 2
OTUB2 increases the amount of SP1. 2 / 2
| 2
reach
"OTUB2 upregulated the protein expression of SP1 by inhibiting its ubiquitination degradation, thereby promoting the transcriptional activity of GINS1 and subsequently enhancing the stemness feature of colon cancer."
39210373
reach
"Consequently, we hypothesized that OTUB2 enhanced the stability of SP1 protein expression by deubiquitinating it, thereby promoting the transcriptional activity of GINS1."
39210373
OTUB2 inhibits SP1.
| 1
OTUB2 inhibits SP1. 1 / 1
| 1
reach
"The specific ubiquitin chains that OTUB2 could inhibit to exert its deubiquitinating effect on the SP1 protein remain unknown."
39210373
OTUB2 activates Neoplasm Invasiveness.
| 8
reach
"The overexpression of OTUB2 promoted glycolysis and induced the proliferation, migration, and invasion of endometrial cancer cells."
36316812
reach
"These results indicated that OTUB2-regulated expression of CTNNB1 could enhance ZEB1 to promote the invasion and metastasis of iCCA cells.To further investigate the mechanism of CTNNB1 upregulation in[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36858343
reach
"Moreover, knockdown of OTUB2 significantly suppressed the invasion and migration abilities of A549 and H1299 cells."
30662561
reach
"We also confirmed that OTUB2 enhanced the proliferation, migration, and invasion abilities of NSCLC cells In vitro."
30662561
reach
"In contrast, stable overexpression of OTUB2 significantly increased the invasion and migratory abilities of XL-2 and H292 cells."
30662561
reach
"Overexpression of OTUB2 enhanced glycolysis and promoted cell growth, migration, and invasion via the AKT/mTOR signaling pathway in A549 and H1299 cells and a xenograft mouse model (Li J. et al., 2019)."
36532721
reach
"These results indicate that OTUB2-regulated expression of ZEB1 enhances EMT to promote invasion and metastasis in iCCA cells ( Fig. 4 E and F)."
36858343
reach
"Meanwhile, in vitro experiments confirmed that the reduction in cell migration and invasion ability caused by low OTUB2 expression could be attenuated by CTNNB1 overexpression."
36858343
OTUB2 inhibits Neoplasm Invasiveness. 1 / 1
| 1
reach
"Depletion of OTUB2 promotes CD8 + CTL-mediated killing of tumor cells and enhances intratumoral T-cell infiltration."
38167274
OTUB2 affects AKT
| 7 2
OTUB2 activates AKT.
| 4 2
OTUB2 activates AKT. 6 / 6
| 4 2
reach
"OTUB2 increases the activity of the glycolytic enzyme PGK1 and activates Akt/mTOR signalling pathways to promote the Warburg effect in NSCLC by stabilising U2AF2 [49] ."
35031261
reach
"Since OTUB2 can promote cancer progression by regulating Hippo, NF-kB and Akt/mTOR pathways , we next investigated the effects of OTUB2-IN-1 on regulating Hippo, NF-κB and Akt/mTOR pathways."
38167274
sparser
"Based on these findings, we hypothesized that OTUB2 activates AKT by deubiquitinating TRAF6, thereby exerting a pro-oncogenic effect."
40296903
reach
"Inhibition of OTUB2 promotes apoptosis and attenuates proliferation and metastasis of CC cells by downregulating the AKT/mTOR signalling pathway (Ref."
39377535
reach
"The researchers also investigated the relationship between OTUB2 and KRT80 and the AKT pathway and found that both OTUB2 and KRT80 can activate the AKT pathway."
37211956
sparser
"OTUB2 deubiquitinates TRAF6 and activates AKT."
40296903
OTUB2 inhibits AKT.
| 3
OTUB2 inhibits AKT. 3 / 3
| 3
reach
"Inhibition of OTUB2 promotes apoptosis and attenuates proliferation and metastasis of CC cells by downregulating the AKT/mTOR signalling pathway (Ref."
39377535
reach
"However, differential regulation of Hippo signaling, AKT/mTOR signaling and NF-κB signaling by OTUB2 inhibition was observed in different tumors."
38167274
reach
"In addition, OTUB2 inhibition deactivated the AKT/mTOR signaling in CC cells."
37334762
SUMO3 affects OTUB2
1 | 7
SUMO3 binds OTUB2. 8 / 8
1 | 7
sparser
"Indeed, while purified YAP and TAZ wild-type directly associated with OTUB2-SUMO3 chimera, whereas the SIM3A mutants of YAP or TAZ could not ( Figure 6 D)."
30472188
biogrid
No evidence text available
30472188
sparser
"In line with the above findings, the OTUB2-SUMO3 chimera more efficiently increased the stability of YAP/TAZ than OTUB2-WT, whereas OTUB2-K233R was much less efficient to stabilize YAP/TAZ ( Figures S[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
sparser
"Analysis of OTUB2 self-deubiquitination and the activity for Ubiquitin-AMC showed that both OTUB2-K233R and the OTUB2-SUMO3 chimera displayed similar deubiquitinating activity ( Figures S5 C and S5D),[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
sparser
"Moreover, expression of OTUB2-WT or OTUB2-SUMO3 could not increase mammosphere numbers in cells expressing YAP/TAZ-SIM3A ( Figures S6 F and S6G), indicating that the SIM of YAP/TAZ is required to func[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
sparser
"Moreover, although purified YAP/TAZ could not directly interact with OTUB2-WT in vitro , it did bind OTUB2-SUMO chimera that might mimic SUMOylation (OTUB2-SUMO3; Figure 5 B)."
30472188
sparser
"Furthermore, breast cancer cells stably expressing the OTUB2-SUMO3 chimera showed more mammospheres and CD44 high /CD24 low stem-like cells, whereas OTUB2-K233R expression had the opposite effect ( Fi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
sparser
"Consistent with this, YAP/TAZ ubiquitination was not reduced by OTUB2-K233R, whereas the OTUB2-SUMO3 chimera was more active than OTUB2-WT to reduce YAP/TAZ ubiquitination ( Figures 5 C, 5D, S5 A, and[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
OTUB2 affects lactate
| 1 7
OTUB2 activates lactate.
| 1 5
OTUB2 activates lactate. 6 / 6
| 1 5
reach
"Fourth, although we determined that OTUB2 promoted glycolysis and increased the lactate content in VSMCs, we did not investigate whether OTUB2 regulates histone lactylation levels during VC progression."
39776804
eidos
"Moreover , OTUB2 depletion reduces glucose consumption , lactate production , and cellular ATP production ."
34671086
reach
"Conversely, OTUB2 overexpression substantially enhanced glycolytic capability, glucose uptake and extracellular lactate production in XL-2 and H292 cells."
30662561
reach
"As expected, we verified that OTUB2 overexpression increased ECAR, glucose uptake, and lactate production, while knockdown of OTUB2 impaired the aerobic glycolytic phenotype in different NSCLC cell lines."
30662561
reach
"Moreover, OTUB2 depletion reduces glucose consumption, lactate production, and cellular ATP production."
34671086
reach
"Analyses using a Seahorse XF96 analyzer revealed that OTUB2 deficiency suppressed glycolytic flux and decreased the production of lactate."
39776804
OTUB2 inhibits lactate.
| 2
OTUB2 inhibits lactate. 2 / 2
| 2
reach
"Overexpression of OTUB2 or SNX29P2 in ES-2 cells inhibited glycolysis and lactate production while increasing OXPHOS (Fig. 4 C–E and SI Appendix, Fig. S4 A–C)."
38701117
reach
"The results indicated that silencing OTUB2 significantly increased glycolytic capacity and lactate production and inhibited OXPHOS (Fig. 4 F–H and SI Appendix, Fig. S4 E and F)."
38701117
OTUB2 affects SUMO3
1 | 7
SUMO3 binds OTUB2. 8 / 8
1 | 7
sparser
"Indeed, while purified YAP and TAZ wild-type directly associated with OTUB2-SUMO3 chimera, whereas the SIM3A mutants of YAP or TAZ could not ( Figure 6 D)."
30472188
biogrid
No evidence text available
30472188
sparser
"In line with the above findings, the OTUB2-SUMO3 chimera more efficiently increased the stability of YAP/TAZ than OTUB2-WT, whereas OTUB2-K233R was much less efficient to stabilize YAP/TAZ ( Figures S[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
sparser
"Analysis of OTUB2 self-deubiquitination and the activity for Ubiquitin-AMC showed that both OTUB2-K233R and the OTUB2-SUMO3 chimera displayed similar deubiquitinating activity ( Figures S5 C and S5D),[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
sparser
"Moreover, expression of OTUB2-WT or OTUB2-SUMO3 could not increase mammosphere numbers in cells expressing YAP/TAZ-SIM3A ( Figures S6 F and S6G), indicating that the SIM of YAP/TAZ is required to func[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
sparser
"Moreover, although purified YAP/TAZ could not directly interact with OTUB2-WT in vitro , it did bind OTUB2-SUMO chimera that might mimic SUMOylation (OTUB2-SUMO3; Figure 5 B)."
30472188
sparser
"Furthermore, breast cancer cells stably expressing the OTUB2-SUMO3 chimera showed more mammospheres and CD44 high /CD24 low stem-like cells, whereas OTUB2-K233R expression had the opposite effect ( Fi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
sparser
"Consistent with this, YAP/TAZ ubiquitination was not reduced by OTUB2-K233R, whereas the OTUB2-SUMO3 chimera was more active than OTUB2-WT to reduce YAP/TAZ ubiquitination ( Figures 5 C, 5D, S5 A, and[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
OTUB2 affects NFkappaB
| 5
OTUB2 activates NFkappaB.
| 4
OTUB2 activates NFkappaB. 4 / 5
| 4
reach
"Since OTUB2 can promote cancer progression by regulating Hippo, NF-kB and Akt/mTOR pathways , we next investigated the effects of OTUB2-IN-1 on regulating Hippo, NF-κB and Akt/mTOR pathways."
38167274
reach
"Mechanistically, OTUB2 overexpression can activate NF-kappaB signaling mostly by stabilizing TRAF6."
30588107
reach
"Knockdown of otubain 2 inhibits liver cancer cell growth by suppressing NF-kappaB signaling."
32003539
reach
"Our further investigations revealed that knockdown of OTUB2 significantly suppressed NF-kappaB-driving luciferase activity, and markedly inhibited the phosphorylation of NF-kappaB p65 in liver cancer cells, which indicated that OTUB2 mediated liver cancer cell growth by regulating NF-kappaB signaling."
32003539
OTUB2 inhibits NFkappaB.
| 1
OTUB2 inhibits NFkappaB. 1 / 3
| 1
reach
"Overexpression of OTUB1 and OTUB2 inhibited virus induced activation of IRF3 and NF-kappaB, transcription of the IFNB1 gene as well as cellular antiviral response, whereas knockdown of OTUB1 and OTUB2 had opposite effects."
19996094
OTUB2 affects CALML3
| 5 3
OTUB2 activates CALML3.
| 3 3
OTUB2 activates CALML3. 6 / 6
| 3 3
sparser
"Our previous results suggested that OTUB2 activates CALML3 at the transcriptional level."
36288705
reach
"To validate the existence of TFs that mediate the activation of CALML3 by OTUB2, immunoprecipitation (IP) experiments in KYSE30 and UM1 cells expressing Myc-OTUB2 proteins were performed using anti-My[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36288705
sparser
"In oral and esophageal squamous cell carcinomas, OTUB2 activates CALML3 ( xref ), a specific marker of the squamous epithelium ( xref xref – xref ), to exert its tumor-suppressive effects."
38701117
sparser
"To validate the existence of TFs that mediate the activation of CALML3 by OTUB2, immunoprecipitation (IP) experiments in KYSE30 and UM1 cells expressing Myc-OTUB2 proteins were performed using anti-My[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36288705
reach
"In oral and esophageal squamous cell carcinomas, OTUB2 activates CALML3 (34), a specific marker of the squamous epithelium (42–44), to exert its tumor-suppressive effects."
38701117
reach
"Furthermore, treatment of cells with the Ca 2+ channel inhibitor ruthenium red completely abolished the elevated PS synthesis triggered by OTUB2 or CALML3 overexpression ( Figure S3 H), proving the cr[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36288705
OTUB2 increases the amount of CALML3.
| 2
OTUB2 increases the amount of CALML3. 2 / 2
| 2
reach
"In contrast, Chang et al. [56] discovered that OTUB2 is missing in ESCC tissues, while OTUB2 can deubiquitinate STAT1 and phosphorylate it, thereby activating CALML3 transcription and phospholipid acetylserine synthesis to exert tumor suppressive effects."
38819228
reach
"Moreover, OTUB2 promotes the interaction between STAT1 and JAKs, increases STAT1 phosphorylation at Tyr701, and augments the transcriptional activity of STAT1 to activate CALML3 expression."
36288705
OTUB2 affects MTOR
| 7
OTUB2 activates MTOR.
| 4
OTUB2 activates MTOR. 4 / 4
| 4
reach
"Inhibition of OTUB2 promotes apoptosis and attenuates proliferation and metastasis of CC cells by downregulating the AKT/mTOR signalling pathway (Ref."
39377535
reach
"Since OTUB2 can promote cancer progression by regulating Hippo, NF-kB and Akt/mTOR pathways , we next investigated the effects of OTUB2-IN-1 on regulating Hippo, NF-κB and Akt/mTOR pathways."
38167274
reach
"The phosphorylation levels of mTOR and AKT were increased, indicating that the mTOR pathway may be activated by OTUB2."
30662561
reach
"OTUB2 increases the activity of the glycolytic enzyme PGK1 and activates Akt/mTOR signalling pathways to promote the Warburg effect in NSCLC by stabilising U2AF2 [49] ."
35031261
OTUB2 inhibits MTOR.
| 3
OTUB2 inhibits MTOR. 3 / 3
| 3
reach
"In addition, OTUB2 inhibition deactivated the AKT/mTOR signaling in CC cells."
37334762
reach
"However, differential regulation of Hippo signaling, AKT/mTOR signaling and NF-κB signaling by OTUB2 inhibition was observed in different tumors."
38167274
reach
"Inhibition of OTUB2 promotes apoptosis and attenuates proliferation and metastasis of CC cells by downregulating the AKT/mTOR signalling pathway (Ref."
39377535
OTUB2 affects COV1
| 1 6
COV1 binds OTUB2. 7 / 7
| 1 6
sparser
"For example, OTUB2-COV-1 targets the active Cys51 of OTUB2, and NUDT7-COV-1 targets C73 of NUDT7 [ xref ]."
36431829
sparser
"Further fragment analogue evaluation yielded the best inhibitor OTUB2-COV-1 ( xref ) with the k inact / K I value of 3.75 M −1 s −1 ."
34458789
sparser
"IsoTOP-ABPP demonstrated that OTUB2-COV-1 (10 μM compound, 2 h incubation) labeled <1% probe-accessible cysteines (Heavy/Light ratio >4) in HEK293T cells suggesting promising selectivity profile suitable for further development."
34458789
sparser
"Small molecule inhibitors for OTUB2 (OTUB2-COV-1) [ xref ] and USP4 (NR) [ xref ] have also been identified."
35204803
sparser
"Recently, the first highly selective OTUB2 covalent inhibitor named OTUB2-COV-1 ( 38 , xref ) was identified by combining a new high-throughput thiol-reactivity assay with high-throughput crystallography [ xref ]."
32196552
reach
"In contrast to the co-crystal structure of the OTUB2-COV-1 complex (PDB 5QIO), a clear density for the cyclopropyl-phenyl moiety in our OTUB2-LN5P45 co-crystal structure was detected, which is likely due to the fact that LN5P45 has the defined (1S,2S) configuration."
37642399
sparser
"In contrast to the co-crystal structure of the OTUB2-COV-1 complex (PDB), a clear density for the cyclopropyl-phenyl moiety in our OTUB2- LN5P45 co-crystal structure was detected, which is likely due to the fact that LN5P45 has the defined (1 S ,2 S ) configuration."
37642399
KRAS affects OTUB2
| 4 3
KRAS leads to the sumoylation of OTUB2. 5 / 5
| 2 3
sparser
"Interestingly, the SUMOylation of OTUB2 is induced by EGF and KRAS [ xref ]."
38136274
reach
"Interestingly, the SUMOylation of OTUB2 is induced by EGF and KRAS [78]."
38136274
reach
"Poly-SUMOylated OTUB2, which was induced by Epidermal growth factor (EGF) and oncogenic KRAS, was shown to bind and activate YAP/TAZ promoting tumor metastasis [68]."
31619007
sparser
"Furthermore, OTUB2 sumoylation is stimulated by EGF and oncogenic KRAS, which is essential for EGF and KRAS to stabilize Yap/Taz ( xref )."
33869224
sparser
"Importantly, EGF and oncogenic KRAS induce OTUB2 poly-SUMOylation and thereby activate YAP/TAZ."
36264492
Mutated KRAS leads to the sumoylation of OTUB2. 2 / 2
| 2
reach
"Moreover, OTUB2 poly-SUMOylation was stimulated by epidermal growth factor (EGF) and oncogenic KRAS mutation."
30472188
reach
"In this study we discovered that OTUB2 SUMOylation is promoted by KRAS mutation."
30472188
COV1 affects OTUB2
| 1 6
COV1 binds OTUB2. 7 / 7
| 1 6
sparser
"For example, OTUB2-COV-1 targets the active Cys51 of OTUB2, and NUDT7-COV-1 targets C73 of NUDT7 [ xref ]."
36431829
sparser
"Further fragment analogue evaluation yielded the best inhibitor OTUB2-COV-1 ( xref ) with the k inact / K I value of 3.75 M −1 s −1 ."
34458789
sparser
"IsoTOP-ABPP demonstrated that OTUB2-COV-1 (10 μM compound, 2 h incubation) labeled <1% probe-accessible cysteines (Heavy/Light ratio >4) in HEK293T cells suggesting promising selectivity profile suitable for further development."
34458789
sparser
"Small molecule inhibitors for OTUB2 (OTUB2-COV-1) [ xref ] and USP4 (NR) [ xref ] have also been identified."
35204803
sparser
"Recently, the first highly selective OTUB2 covalent inhibitor named OTUB2-COV-1 ( 38 , xref ) was identified by combining a new high-throughput thiol-reactivity assay with high-throughput crystallography [ xref ]."
32196552
reach
"In contrast to the co-crystal structure of the OTUB2-COV-1 complex (PDB 5QIO), a clear density for the cyclopropyl-phenyl moiety in our OTUB2-LN5P45 co-crystal structure was detected, which is likely due to the fact that LN5P45 has the defined (1S,2S) configuration."
37642399
sparser
"In contrast to the co-crystal structure of the OTUB2-COV-1 complex (PDB), a clear density for the cyclopropyl-phenyl moiety in our OTUB2- LN5P45 co-crystal structure was detected, which is likely due to the fact that LN5P45 has the defined (1 S ,2 S ) configuration."
37642399
2,3,7,8-tetrachlorodibenzodioxine increases the amount of OTUB2.
6 |
2,3,7,8-tetrachlorodibenzodioxine increases the amount of OTUB2. 6 / 6
6 |
ctd
No evidence text available
33387578
ctd
No evidence text available
21215274
ctd
No evidence text available
17942748
ctd
No evidence text available
29704546
ctd
No evidence text available
21632981
ctd
No evidence text available
20106945
2,3,7,8-tetrachlorodibenzodioxine decreases the amount of OTUB2.
1 |
2,3,7,8-tetrachlorodibenzodioxine decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
29704546
UBC affects OTUB2
6 |
OTUB2 binds UBC. 6 / 6
6 |
biogrid
No evidence text available
25590432
biogrid
No evidence text available
23827681
biogrid
No evidence text available
18954305
biogrid
No evidence text available
31494268
biogrid
No evidence text available
29576527
biogrid
No evidence text available
25590432
SP1 affects OTUB2
1 | 2 3
SP1 binds OTUB2. 6 / 6
1 | 2 3
sparser
"Additionally, the results from endogenous and exogenous co-immunoprecipitation (CO-IP) experiments further supported the interaction between OTUB2 protein and SP1 protein (Fig.  xref C, D)."
39210373
reach
"Confocal microscopy results also revealed the binding between OTUB2 and SP1 in colon cancer cells (Fig. 5B)."
39210373
reach
"Second, while we have demonstrated that OTUB2 can inhibit K48 ubiquitination-mediated degradation of SP1 and upregulate its expression, it remains unknown whether OTUB2 competitively binds to the ubiquitin or E3 ubiquitin ligase binding site on SP1."
39210373
sparser
"OTUB2 interacted with SP1 to suppress its K48 ubiquitination, thereby upregulating its protein expression level."
39210373
sparser
"First, although we have shown that SP1 is a target protein of OTUB2, we have not further identified the specific structural domain or binding site where OTUB2 interacts with SP1."
39210373
biogrid
No evidence text available
35140242
PKM affects OTUB2
6 |
OTUB2 binds PKM. 6 / 6
6 |
biogrid
No evidence text available
30662561
biogrid
No evidence text available
34671086
biogrid
No evidence text available
34671086
biogrid
No evidence text available
34671086
biogrid
No evidence text available
34671086
biogrid
No evidence text available
34671086
OTUB2 affects pathway
| 6
OTUB2 activates pathway. 6 / 6
| 6
sparser
"Perhaps OTUB2 can activate the Akt pathway on its own without requiring KRT80?"
35110531
sparser
"Besides that, OTUB2 activates the Akt pathway, suggesting that it may be a novel therapeutic and prognostic target in GC."
35110531
sparser
"MKN45 cells express a high level of OTUB2 but very little Ki67 and p-Akt (Thr308), indicating that OTUB2 does not activate the Akt pathway on its own, but via KRT80."
35110531
sparser
"The researchers also investigated the relationship between OTUB2 and KRT80 and the AKT pathway and found that both OTUB2 and KRT80 can activate the AKT pathway."
37211956
sparser
"In conclusion, KRT80 is deubiquitinated by OTUB2, which activates the PI3K/AKT pathway that promotes gastric cancer cell proliferation and growth; KRT80 is essential in this process (Figure  xref ). xref Correlation analysis in 90 GC patients showed that high OTUB2 expression levels were positively correlated with tumor T stage, AJCC stage, and degree of differentiation."
37211956
sparser
"As mentioned above, OTUB2 can stably activate the NF-kappaB pathway through K48 type deubiquitination of TRAF6 and maintenance of phosphorylated p65, resulting in pathological manifestations of cancer."
35309903
reach
"OTUB2 enables the initiation of HR by suppressing the excessive accumulation of 53BP1 and RAP80 in an early phase of the DDR [XREF_BIBR, XREF_BIBR]."
30831436
reach
"Thus, the RNF8-RNF168 axis primarily suppresses HR and promotes non-HR-type DSB repair, e.g. NHEJ, and OTUB2 enables the initiation of HR by suppressing the excessive accumulation of 53BP1 and RAP80 in an early phase of the DDR."
26983989
reach
"OTUB1 binds Ubc13 (UBE2N) to inhibit K63-linked-ubiquitination of chromatin in DSB repair, whereas its ohnolog, OTUB2, shows much lower affinity for Ubc13 and instead promotes HR by interacting with another novel ohnolog, L3MBTL1."
28177072
reach
"doi:10.1177/0963689720929983.Wan Q, Chen Q, Cai D, Zhao Y, Wu X. OTUB2 promotes homologous recombination repair through stimulating Rad51 expression in endometrial cancer."
39601276
reach
"They also found that OTUB2 may be an important upstream regulator of YAP/TAZ expression, regulating the development of tumors by affecting the protein expression of YAP/TAZ, which has almost no effect on YAP/TAZ mRNA levels.It has also been reported that OTUB2 promotes homologous recombination repair of endometrial carcinoma through YAP/TAZ mediated Rad51 expression, which provides a potential therapeutic target for endometrial carcinoma."
35850645
reach
"Taking these findings together, we propose a model whereby OTUB2 inhibits excessive DSB-end protection and allows the initiation of HR by properly regulating the accumulation of RAP80 and 53BP1 at DSB[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24560272
OTUB2 affects chloroethene
| 6
OTUB2 activates chloroethene. 6 / 6
| 6
reach
"Since OTUB2 modulates YAP activity and VC progression, we next sought to investigate the potential regulatory mechanisms between OTUB2 and YAP."
39776804
reach
"The knockdown or inhibition of PFKFB3 alleviated the procalcific effects of OTUB2.Conclusions: Our findings indicate that OTUB2 promotes VC at least partially by activating the YAP-PFKFB3 signaling pathway."
39776804
reach
"In this study, we revealed that OTUB2 promoted VSMC osteogenic differentiation and aggravated VC both in vivo and in vitro."
39776804
reach
"OTUB2 accelerates the development of VC."
39776804
reach
"Given that OTUB2 is upregulated during VC development, we next sought to evaluate whether OTUB2 overexpression might accelerate VC."
39776804
reach
"Knockdown or inhibition of YAP partially suppresses VC promoted by OTUB2 overexpression."
39776804
OTUB2 affects cell growth
| 6
OTUB2 activates cell growth. 6 / 6
| 6
reach
"At the cellular level, knockdown of OTUB2 markedly inhibited liver cancer cell growth."
32003539
reach
"Knockdown of OTUB2 suppressed CC cell growth whereas OTUB2 upregulation fostered the proliferation of cancer cells."
38322554
reach
"Inhibition of OTUB2 suppresses colorectal cancer cell growth by regulating β-Catenin signaling."
38058843
reach
"The results demonstrated that OTUB2 knockdown significantly inhibited TNBC cell growth, while overexpression promoted cell growth in a time-dependent manner (Fig. 3A,B)."
40296903
reach
"Overexpression of OTUB2 enhanced glycolysis and promoted cell growth, migration, and invasion via the AKT/mTOR signaling pathway in A549 and H1299 cells and a xenograft mouse model (Li J. et al., 2019)."
36532721
reach
"Our further investigations revealed that knockdown of OTUB2 significantly suppressed NF-kappaB-driving luciferase activity, and markedly inhibited the phosphorylation of NF-kappaB p65 in liver cancer cells, which indicated that OTUB2 mediated liver cancer cell growth by regulating NF-kappaB signaling."
32003539
OTUB2 affects UBC
6 |
OTUB2 binds UBC. 6 / 6
6 |
biogrid
No evidence text available
25590432
biogrid
No evidence text available
23827681
biogrid
No evidence text available
18954305
biogrid
No evidence text available
31494268
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No evidence text available
29576527
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No evidence text available
25590432
OTUB2 affects PKM
6 |
OTUB2 binds PKM. 6 / 6
6 |
biogrid
No evidence text available
30662561
biogrid
No evidence text available
34671086
biogrid
No evidence text available
34671086
biogrid
No evidence text available
34671086
biogrid
No evidence text available
34671086
biogrid
No evidence text available
34671086
OTUB2 affects NR4A1
1 | 3 2
OTUB2 binds NR4A1.
1 | 2 2
OTUB2 binds NR4A1. 4 / 4
1 | 1 2
sparser
"We also observed that OTUB2 also bind to Nur77 ( Fig. 4 D)."
30905540
reach
"That is, OTUB2 also bound Nur77 and was shown to increase the stability of Nur77 as shown by the CHX chase experiment."
30905540
biogrid
No evidence text available
30905540
sparser
"That is, OTUB2 also bound Nur77 and was shown to increase the stability of Nur77 as shown by the CHX chase experiment."
30905540
OTUB2 binds NR4A1 and 4 D. 1 / 1
| 1
reach
"We also observed that OTUB2 also bind to Nur77 ( Fig. 4 D)."
30905540
OTUB2 activates NR4A1.
| 1
OTUB2 activates NR4A1. 1 / 1
| 1
reach
"That is, OTUB1 or OTUB2 suppressed Nur77 degradation which was increased by CHX treatment ( Fig. 4 C)."
30905540
STAT1 affects OTUB2
| 3 2
STAT1 binds OTUB2.
| 2 2
OTUB2 binds STAT1. 4 / 4
| 2 2
reach
"Mechanistically, OTUB2 cleaves K6- and K63-associated ubiquitin linkages on signal transducer and activator of transcription 1 (STAT1), resulting in enhanced phosphorylation at Tyr701, dimerization, a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36288705
sparser
"The above results indicated that the interaction between OTUB2 and STAT1 is dependent on the enzymatic activity of OTUB2."
36288705
reach
"The above results indicated that the interaction between OTUB2 and STAT1 is dependent on the enzymatic activity of OTUB2."
36288705
sparser
"We found that OTUB2 specifically interacts with STAT1 and primarily cleaves K6- and K63-linked ubiquitin chains on STAT1."
36288705
STAT1 activates OTUB2.
| 1
STAT1 activates OTUB2. 1 / 1
| 1
reach
"Accordingly, STAT1 depletion abolished the tumor-suppressive effects of OTUB2 ( Figures S4 C–S4E)."
36288705
reach
"Finally, Western blotting experiments, Transwell migration assays, and wound healing assays indicated that OTUB2 knockdown reduced EMT and migration ability of colon cancer cells, which could be restored by GINS1 overexpression."
39210373
reach
"Additionally, Western blotting assays along with Transwell migration assays and wound healing assays verified that EMT process as well as migration ability in colon cancer cells were suppressed by OTUB2 knockdown but could be rescued through SP1 overexpression, and vice versa (Fig. S8C-E)."
39210373
reach
"These results indicate that OTUB2-regulated expression of ZEB1 enhances EMT to promote invasion and metastasis in iCCA cells ( Fig. 4 E and F)."
36858343
reach
"OTU deubiquitinase, ubiquitin aldehyde binding 2 (OTUB2) modulates the stemness feature, chemoresistance, and epithelial-mesenchymal transition of colon cancer via regulating GINS complex subunit 1 (GINS1) expression."
39210373
OTUB2 inhibits epithelial to mesenchymal transition. 1 / 1
| 1
reach
"However, upon addition of the EMT activator (TGF-β), we observed a reversal of changes in the expression levels of these EMT biomarkers caused by OTUB2 knockdown (Fig. 3C)."
39210373
OTUB2 affects cell migration
| 5
OTUB2 activates cell migration.
| 4
OTUB2 activates cell migration. 4 / 4
| 4
reach
"Knockdown of OTUB2 significantly inhibited cell migration and invasive ability, and ZEB1 overexpression could reverse this phenomenon as confirmed in in vitro experiments."
36858343
reach
"Additionally, while our findings suggest that OTUB2 promotes TNBC cell migration, this conclusion is based solely on in vitro assays, and we lack in vivo metastasis models to further validate its role in tumor dissemination."
40296903
reach
"Conversely, the knockdown of OTUB2 resulted in slower wound healing, reinforcing the Transwell results and confirming that OTUB2 depletion inhibits TNBC cell migration (Fig. 4E,F)."
40296903
reach
"Meanwhile, in vitro experiments confirmed that the reduction in cell migration and invasion ability caused by low OTUB2 expression could be attenuated by CTNNB1 overexpression."
36858343
OTUB2 inhibits cell migration.
| 1
OTUB2 inhibits cell migration. 1 / 1
| 1
reach
"We next found that downregulation of OTUB2 decreased cell migration and invasion ( Fig. 2 D and E)."
36858343
OTUB2 affects RIPK2
| 3 2
OTUB2 binds RIPK2.
| 2
OTUB2 binds RIPK2. 2 / 2
| 2
sparser
"RIPK2 was detected in the immunocomplex harvested from BMDMs with anti‐OTUB2 antibody (Figure  xref ), showing that RIPK2 interacts with OTUB2."
39358938
sparser
"To determine the mechanism how OTUB2 stabilises RIPK2, we then examined whether OTUB2 directly interacted with RIPK2."
39358938
OTUB2 activates RIPK2.
| 2
OTUB2 activates RIPK2. 2 / 2
| 2
reach
"Mechanistically, OTUB2 inhibited the proteasomal degradation of RIPK2 by removing K48-linked polyubiquitination on RIPK2, which was mediated by the active C51 residue in OTUB2."
39358938
reach
"Upon MDP stimulation, OTUB2 promoted NOD2 signaling by stabilizing RIPK2."
39358938
OTUB2 deubiquitinates RIPK2.
| 1
OTUB2 deubiquitinates RIPK2. 1 / 1
| 1
reach
"Deubiquitination of RIPK2 by OTUB2 augments NOD2 signalling and protective effects in intestinal inflammation."
39358938
OTUB2 affects PRRT2
| 5
OTUB2 activates PRRT2.
| 4
OTUB2 activates PRRT2. 4 / 4
| 4
reach
"These indicate that OTUB2 promotes the metastasis of iCCA cells through ZEB1-regulated EMT.CTNNB1 signaling is involved in many physiological and pathological processes, as shown in previous works [ 2[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36858343
reach
"These results indicate that OTUB2-regulated expression of ZEB1 enhances EMT to promote invasion and metastasis in iCCA cells ( Fig. 4 E and F)."
36858343
reach
"Therefore, we next sought to ascertain the underlying molecular mechanism of OTUB2-mediated iCCA pathogenesis.Previous studies established that ZEB1 promotes the metastasis of AML and kidney and pancr[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36858343
reach
"The present work demonstrated that OTUB2 knockdown significantly inhibited the proliferation of iCCA cells while promoting apoptosis, suggesting that increased cell proliferation and decreased apoptos[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36858343
OTUB2 binds PRRT2.
| 1
OTUB2 binds PRRT2. 1 / 1
| 1
reach
"The direct binding of OTUB2 to CTNNB1 in iCCA cells was verified by a Co-IP assay, and overexpression of CTNNB1 in cells with OTUB2 knockdown could rescue ZEB1 expression."
36858343
OTUB2 affects PJA1
2 | 3
OTUB2 activates PJA1.
| 3
OTUB2 activates PJA1. 3 / 3
| 3
reach
"Mechanistically, it was found that OTUB2 promoted the stabilization of PJA1 by deubiquitylation, based on immunoprecipitation (IP) and cycloheximide (CHX) assays."
35611163
reach
"Moreover, the suppressive effects of OTUB2 depletion on the malignant phenotypes of HCC cells could be reversed by overexpressing PJA1."
35611163
reach
"In conclusion, our study indicated that OTUB2 could promote the malignant proliferation and migration of HCC cells by increasing the stability of PJA1 via deubiquitylation."
35611163
OTUB2 binds PJA1.
2 |
PJA1 binds OTUB2. 2 / 2
2 |
biogrid
No evidence text available
35611163
biogrid
No evidence text available
22626734
OTUB2 affects PFKFB3
| 5
OTUB2 increases the amount of PFKFB3. 5 / 5
| 5
reach
"Collectively, these data indicated that OTUB2 promotes glycolysis in VSMCs by regulating PFKFB3 expression."
39776804
reach
"CUT&RUN-qPCR assays showed that OTUB2 silencing suppressed the YAP/TEAD1-promoted transcription of PFKFB3."
39776804
reach
"OTUB2 contributes to vascular calcification in chronic kidney disease via the YAP-mediated transcription of PFKFB3."
39776804
reach
"In the present study, we found that OTUB2-mediated YAP stabilization promotes PFKFB3 transcription, thereby accelerating VC in CKD."
39776804
reach
"OTUB2 facilitates PFKFB3 transcription through YAP."
39776804
OTUB2 affects GINS1
| 4 1
OTUB2 binds GINS1.
| 1 1
OTUB2 binds GINS1. 2 / 2
| 1 1
sparser
"Therefore, we postulated that there might be other key molecules involved in the interaction between OTUB2 and GINS1."
39210373
reach
"Therefore, we postulated that there might be other key molecules involved in the interaction between OTUB2 and GINS1."
39210373
OTUB2 activates GINS1.
| 2
OTUB2 activates GINS1. 2 / 2
| 2
reach
"Further investigations revealed that OTUB2 mediated the malignant progression of colon cancer by regulating GINS1."
39210373
reach
"Therefore, we also intended to investigate whether OTUB2 enhances the stem cell properties of colon cancer cells by modulating GINS1, thereby promoting chemotherapy resistance and EMT.SP1 can be categorized into four domains based on their respective functions: the dsDNA binding domain, the SP1 transcriptional activity domain, the Btd domain, and the SP domain [23]."
39210373
OTUB2 increases the amount of GINS1.
| 1
OTUB2 increases the amount of GINS1. 1 / 1
| 1
reach
"OTUB2 modulated stemness feature, chemosensitivity, and EMT of colon cancer cells through regulating GINS1 expression."
39210373
OTUB2 affects CS
| 5
CS binds OTUB2. 5 / 5
| 5
sparser
"H&E and immunohistochemistry (IHC) staining indicated enhanced YAP/TAZ levels in the OTUB2-WT group, but not in the OTUB2-CS and OTUB2-KR groups ( Figure 5 H)."
30472188
sparser
"Consistent with the idea that OTUB2 serves as a DUB for YAP/TAZ, we found that co-expression of OTUB2-WT, but not OTUB2-CS, decreased YAP/TAZ lysine 48 poly-ubiquitination detected in the presence of [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
sparser
"Pulse-chase labeling experiments showed that ectopic expression of OTUB2-WT, but not OTUB2-CS, prolonged the half-life of endogenous YAP ( Figure 3 L); Consistently, the turnover rate of TAZ as measur[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
sparser
"OTUB2-WT, OTUB2-CS, or OTUB2-K233R (KR) was ectopically expressed in 4T1 murine breast cancer cells, and the cells were injected under the nipple of BALB/c mice, which allowed us to examine both prima[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
sparser
"OTUB2-WT expression increased spontaneous lung metastasis without affecting primary tumor growth, whereas expression of OTUB2-CS or OTUB2-KR had no significant effects ( Figure 5 E–5H)."
30472188
OTUB2 affects CC
| 5
OTUB2 activates CC. 5 / 5
| 5
reach
"Knockdown of OTUB2 suppressed CC cell growth whereas OTUB2 upregulation fostered the proliferation of cancer cells."
38322554
reach
"FOXM1 was found to play a critical role in OTUB2-mediated CC cell growth."
38322554
reach
"OTUB2 promotes CC progression through deubiquitinating and stabilizing FOXM1."
38322554
reach
"Inhibition of OTUB2 promotes apoptosis and attenuates proliferation and metastasis of CC cells by downregulating the AKT/mTOR signalling pathway (Ref."
39377535
reach
"As indicated by CCK-8, Transwell, and flow cytometry results, OTUB2 silencing attenuated proliferative and metastatic capacities of CC cells but promoted CC cell apoptosis."
37334762
NR4A1 affects OTUB2
1 | 2 2
OTUB2 binds NR4A1. 4 / 4
1 | 1 2
sparser
"We also observed that OTUB2 also bind to Nur77 ( Fig. 4 D)."
30905540
reach
"That is, OTUB2 also bound Nur77 and was shown to increase the stability of Nur77 as shown by the CHX chase experiment."
30905540
biogrid
No evidence text available
30905540
sparser
"That is, OTUB2 also bound Nur77 and was shown to increase the stability of Nur77 as shown by the CHX chase experiment."
30905540
OTUB2 binds NR4A1 and 4 D. 1 / 1
| 1
reach
"We also observed that OTUB2 also bind to Nur77 ( Fig. 4 D)."
30905540
LN5P45 affects OTUB2
| 5
LN5P45 inhibits OTUB2.
| 2
LN5P45 inhibits OTUB2. 2 / 2
| 2
reach
"LN5P45 is a small-molecule inhibitor of OTUB2 with high specificity, and it inhibits the DUB activity of OTUB2 by engaging the C51 active site (Appendix Fig. S13B) (Gan et al, 2023)."
40021931
reach
"Since none of the other Rho-Ub-PA-labeled bands were affected by the OTUB2 inhibitor, this result indicates that LN5P45 can specifically inhibit endogenous OTUB2."
37642399
LN5P45 deubiquitinates OTUB2.
| 1
LN5P45 leads to the deubiquitination of OTUB2 on lysine. 1 / 1
| 1
reach
"Importantly, LN5P45 as well as other OTUB2 inhibitors strongly induce monoubiquitination of OTUB2 on lysine 31."
37642399
LN5P45 binds OTUB2.
| 1
LN5P45 binds OTUB2. 1 / 1
| 1
reach
"For crystallization, the covalent LN5P45-OTUB2 complex was generated by incubating 40 μM purified OTUB2 with a five-fold excess of the inhibitor for 1 h at 37 °C in GF buffer (50 mM Tris pH 7.5, 100 mM NaCl, 2 mM TCEP)."
37642399
LN5P45 activates OTUB2.
| 1
LN5P45 activates OTUB2. 1 / 1
| 1
reach
"LN5P45 treatment restored the viability of Otub2 cells to that of Otub2 cells in response to TCZ stimulation (Appendix Fig. S13E)."
40021931
GINS1 affects OTUB2
| 4 1
GINS1 decreases the amount of OTUB2.
| 2
GINS1 decreases the amount of OTUB2. 2 / 2
| 2
reach
"Conversely, the inhibitory effect of oxaliplatin on colon cancer cell proliferation was weakened by OTUB2 overexpression, which could be enhanced by GINS1 knockdown (Fig. S5F)."
39210373
reach
"Conversely, OTUB2 overexpression weakened EMT and migration ability of colon cancer cells but could be restored by GINS1 knockdown (Fig. S6A-C)."
39210373
GINS1 binds OTUB2.
| 1 1
OTUB2 binds GINS1. 2 / 2
| 1 1
sparser
"Therefore, we postulated that there might be other key molecules involved in the interaction between OTUB2 and GINS1."
39210373
reach
"Therefore, we postulated that there might be other key molecules involved in the interaction between OTUB2 and GINS1."
39210373
GINS1 activates OTUB2.
| 1
GINS1 activates OTUB2. 1 / 1
| 1
reach
"In summary, these experiments collectively demonstrated that modulation of GINS1 expression level allowed OTUB2 to regulated the stemness feature, chemosensitivity, and EMT in colon cancer."
39210373
CTNNB1 affects OTUB2
1 | 2 2
CTNNB1 binds OTUB2.
1 | 1 2
OTUB2 binds CTNNB1. 4 / 4
1 | 1 2
biogrid
No evidence text available
30323974
sparser
"We then performed reciprocal co-immunoprecipitations and demonstrated that OTUB2 and β-Catenin bound to each other."
38058843
reach
"The direct binding of OTUB2 to CTNNB1 in iCCA cells was verified by a Co-IP assay, and overexpression of CTNNB1 in cells with OTUB2 knockdown could rescue ZEB1 expression."
36858343
sparser
"The direct binding of OTUB2 to CTNNB1 in iCCA cells was verified by a Co-IP assay, and overexpression of CTNNB1 in cells with OTUB2 knockdown could rescue ZEB1 expression."
36858343
CTNNB1 inhibits OTUB2.
| 1
CTNNB1 inhibits OTUB2. 1 / 1
| 1
reach
"GSEA revealed a significant positive correlation between the OTUB2 and CTNNB1 pathways, and OTUB2 knockdown was induced by a significant decrease in CTNNB1 expression."
36858343
CS affects OTUB2
| 5
CS binds OTUB2. 5 / 5
| 5
sparser
"H&E and immunohistochemistry (IHC) staining indicated enhanced YAP/TAZ levels in the OTUB2-WT group, but not in the OTUB2-CS and OTUB2-KR groups ( Figure 5 H)."
30472188
sparser
"Consistent with the idea that OTUB2 serves as a DUB for YAP/TAZ, we found that co-expression of OTUB2-WT, but not OTUB2-CS, decreased YAP/TAZ lysine 48 poly-ubiquitination detected in the presence of [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
sparser
"Pulse-chase labeling experiments showed that ectopic expression of OTUB2-WT, but not OTUB2-CS, prolonged the half-life of endogenous YAP ( Figure 3 L); Consistently, the turnover rate of TAZ as measur[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
sparser
"OTUB2-WT, OTUB2-CS, or OTUB2-K233R (KR) was ectopically expressed in 4T1 murine breast cancer cells, and the cells were injected under the nipple of BALB/c mice, which allowed us to examine both prima[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
sparser
"OTUB2-WT expression increased spontaneous lung metastasis without affecting primary tumor growth, whereas expression of OTUB2-CS or OTUB2-KR had no significant effects ( Figure 5 E–5H)."
30472188
Valproic acid affects OTUB2
4 |
Valproic acid decreases the amount of OTUB2.
3 |
Valproic acid decreases the amount of OTUB2. 3 / 3
3 |
ctd
No evidence text available
26272509
ctd
No evidence text available
23179753
ctd
No evidence text available
27188386
Valproic acid methylates OTUB2.
1 |
Valproic acid methylates OTUB2. 1 / 1
1 |
ctd
No evidence text available
29154799
Smo-1 affects OTUB2
| 4
OTUB2 binds smo-1. 4 / 4
| 4
sparser
"Sumoylated OTUB2 interacts specifically with yet-unidentified sumo interaction motifs (SIMs) in WW domain-containing transcription factor (TAZ) and Yes-associated protein (YAP) to regulate protein activity and TAZ/YAP polyubiquitination in a Hippo-independent manner."
35110531
sparser
"No OTUB2-SUMO PLA signal was detected for the SUMOylation-deficient mutant K233R ( Figure 4 F), validating the specificity of the SUMO-PLA assay."
30472188
sparser
"Moreover, although purified YAP/TAZ could not directly interact with OTUB2-WT in vitro , it did bind OTUB2-SUMO chimera that might mimic SUMOylation (OTUB2-SUMO3; Figure 5 B)."
30472188
sparser
"Deubiquitination of YAP/TAZ by OTUB2 depends on the presence of a poly-SUMO chain conjugated to OTUB2 lysine 233, as SUMOylation enables OTUB2 interaction with a novel SUMO-interacting motif (SIM) ide[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
Bisphenol A affects OTUB2
4 |
Bisphenol A increases the amount of OTUB2.
2 |
Bisphenol A increases the amount of OTUB2. 2 / 2
2 |
ctd
No evidence text available
32145629
ctd
No evidence text available
26496021
Bisphenol A methylates OTUB2.
1 |
Bisphenol A methylates OTUB2. 1 / 1
1 |
ctd
No evidence text available
28505145
Bisphenol A decreases the amount of OTUB2.
1 |
Bisphenol A decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
32387340
TRAF3 affects OTUB2
1 | 2 1
OTUB2 binds TRAF3. 3 / 3
1 | 2
reach
"OTUB1 and OTUB2 interact with and deubiquitinate TRAF3 and TRAF6, which are required for virus triggered IRF3 and NF-kappaB activation [XREF_BIBR]."
23151130
biogrid
No evidence text available
19996094
reach
"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63 linked polyubiquitin chains."
33511009
OTUB1 binds OTUB2, TRAF3, and TRAF6. 1 / 1
| 1
sparser
"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63‐linked polyubiquitin chains. [ xref ] Because various components are involved in virus‐induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG‐I‐, MDA5‐, and MAVS‐mediated but not TBK1‐ and IRF3‐mediated signaling."
33511009
RIPK3 affects OTUB2
| 1 3
OTUB2 binds RIPK3. 4 / 4
| 1 3
sparser
"Together, these results demonstrate that OTUB2 interacts with RIPK3 and increases the protein abundance of RIPK3 by reducing its degradation."
40021931
sparser
"Co-immunoprecipitation (Co-IP) verified the interaction between endogenous RIPK3 and OTUB2 in HT22 cells (Fig.  xref )."
40021931
sparser
"OTUB2 physically interacts with RIPK3 to inhibit its degradation."
40021931
reach
"Co-immunoprecipitation (Co-IP) verified the interaction between endogenous RIPK3 and OTUB2 in HT22 cells (Fig. 4F)."
40021931
PKM2 affects OTUB2
| 4
OTUB2 binds PKM2. 4 / 4
| 4
sparser
"OTUB2 directly interacts with PKM2 to inhibit its ubiquitination by disrupting the interaction between PKM2 and E3 ubiquitin ligase Parkin, thus enhancing its pyruvate kinase activity and promoting the Warburg effect [ xref ]."
40137167
sparser
"OTUB2, an OTU deubiquitinase, directly interacts with PKM2 and suppresses its ubiquitination via weakening the interaction of PKM2 and Parkin to increase PKM2 activity and glycolysis in colorectal cancer ( xref )."
38910890
sparser
"In colon cancer, OTUB2 interacts with PKM2, enhancing its activity and promoting glycolysis, thereby facilitating colorectal cancer progression [ xref ]."
39380010
sparser
"Moreover, the deubiquitinase OTUB2 directly interacts with PKM2 and inhibits its ubiquitination, resulting in enhanced glycolysis, proliferation and migratory capacity in CRC cells [ xref ]."
39993964
OTUB2 affects smo-1
| 4
OTUB2 binds smo-1. 4 / 4
| 4
sparser
"Sumoylated OTUB2 interacts specifically with yet-unidentified sumo interaction motifs (SIMs) in WW domain-containing transcription factor (TAZ) and Yes-associated protein (YAP) to regulate protein activity and TAZ/YAP polyubiquitination in a Hippo-independent manner."
35110531
sparser
"No OTUB2-SUMO PLA signal was detected for the SUMOylation-deficient mutant K233R ( Figure 4 F), validating the specificity of the SUMO-PLA assay."
30472188
sparser
"Moreover, although purified YAP/TAZ could not directly interact with OTUB2-WT in vitro , it did bind OTUB2-SUMO chimera that might mimic SUMOylation (OTUB2-SUMO3; Figure 5 B)."
30472188
sparser
"Deubiquitination of YAP/TAZ by OTUB2 depends on the presence of a poly-SUMO chain conjugated to OTUB2 lysine 233, as SUMOylation enables OTUB2 interaction with a novel SUMO-interacting motif (SIM) ide[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
reach
"We showed that OTUB2 prevents cancer stemness via elevated OXPHOS and subsequently increased PS synthesis."
36288705
reach
"Furthermore, treatment of cells with the Ca 2+ channel inhibitor ruthenium red completely abolished the elevated PS synthesis triggered by OTUB2 or CALML3 overexpression ( Figure S3 H), proving the cr[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36288705
reach
"Further lipidomic analyses indicated that OTUB2/STAT1 promoted phosphatidylserine (PS) synthesis by activating calmodulin-like protein 3 ( CALML3 )."
36288705
reach
"We next detected intracellular PS levels using ELISAs, and the results showed that OTUB2 significantly elevated the total PS content in a CALML3-dependent manner ( Figures 3 E and 3F)."
36288705
OTUB2 affects TNBC
| 4
OTUB2 activates TNBC. 4 / 4
| 4
reach
"The results demonstrated that OTUB2 knockdown significantly inhibited TNBC cell growth, while overexpression promoted cell growth in a time-dependent manner (Fig. 3A,B)."
40296903
reach
"Additionally, while our findings suggest that OTUB2 promotes TNBC cell migration, this conclusion is based solely on in vitro assays, and we lack in vivo metastasis models to further validate its role in tumor dissemination."
40296903
reach
"OTUB2 promotes TNBC cell proliferation in vitro and tumor growth."
40296903
reach
"Furthermore, overexpression of OTUB2 promoted TNBC cell proliferation and migration, whereas silencing of OTUB2 resulted in the opposite effect."
40296903
OTUB2 affects PGK1
| 2 2
OTUB2 binds PGK1.
| 2
OTUB2 binds U2AF2 and PGK1. 2 / 2
| 2
sparser
"High expression of OTUB2, U2AF2 and PGK1 is significantly associated with worse prognosis in NSCLC patients."
30662561
sparser
"In addition, our results suggest that high expression of OTUB2, U2AF2 and PGK1 is significantly associated with worse prognosis in NSCLC patients."
30662561
OTUB2 increases the amount of PGK1.
| 1
Modified OTUB2 increases the amount of PGK1. 1 / 1
| 1
reach
"Overexpression of OTUB2 upregulated the expression of PFKL and PGK1 in H292 cells and upregulated the expression of HK2, PFKL, PGK1, and PGAM1 in XL-2 cells."
30662561
OTUB2 activates PGK1.
| 1
OTUB2 activates PGK1. 1 / 1
| 1
reach
"OTUB2 increases the activity of the glycolytic enzyme PGK1 and activates Akt/mTOR signalling pathways to promote the Warburg effect in NSCLC by stabilising U2AF2 [49] ."
35031261
OTUB2 affects NSCLC
| 4
OTUB2 activates NSCLC. 4 / 4
| 4
reach
"To investigate the functional roles of U2AF2 in OTUB2 mediated NSCLC progression, we knocked down endogenous U2AF2 via two independent siRNAs in A549 and H1299 cells."
30662561
reach
"More importantly, OTUB2 promoted NSCLC progression, which was largely dependent on the direct binding to and deubiquitination of U2AF2, at least in NSCLC cells."
30662561
reach
"Our current findings suggest that OTUB2 promotes NSCLC progression, which is largely dependent on U2AF2, at least in NSCLC cells."
30662561
reach
"Next, to elucidate the underlying mechanism by which OTUB2 promotes NSCLC progression, a co-immunoprecipitation assay using antibodies against HA was performed in both 293T cells transfected with HA tagged OTUB2 and control cells."
30662561
OTUB2 affects KRT80
| 4
OTUB2 deubiquitinates KRT80.
| 3
OTUB2 deubiquitinates KRT80. 3 / 3
| 3
reach
"In conclusion, KRT80 is deubiquitinated by OTUB2, which activates the PI3K/AKT pathway that promotes gastric cancer cell proliferation and growth; KRT80 is essential in this process (Figure 1)."
37211956
reach
"Studies have reported that OTUB2 facilitates cancer metastasis via activating YAP and TAZ [36] and enhances the proliferation of gastric cancer cells by deubiquitinating KRT80 [37]."
40296903
reach
"Ouyang et al found that KRT80 is deubiquitinated by OTUB2 to activate the PI3K/AKT pathway, which promotes the growth and proliferation of GC cells; KRT80 is essential in this process."
37211956
OTUB2 increases the amount of KRT80.
| 1
OTUB2 increases the amount of KRT80. 1 / 1
| 1
reach
"Ouyang et al. [28] found that OTUB2 promoted gastric cancer cell proliferation by stabilizing KRT80 expression through deubiquitination."
39210373
OTUB2 affects HIF1A
| 4
OTUB2 activates HIF1A.
| 2
OTUB2 activates HIF1A. 2 / 2
| 2
reach
"Collectively, these data indicate that OTUB2 promotes the Warburg effect by modulating HIF1a and c-Myc."
30662561
reach
"OTUB2 may stimulate the Warburg effect by regulating HIF1a and c-Myc in NSCLC cells."
30662561
OTUB2 increases the amount of HIF1A.
| 1
OTUB2 increases the amount of HIF1A. 1 / 1
| 1
reach
"Moreover, it was very intriguing for us to show that OTUB2 promoted the protein expression of HIF1a and c-Myc and induced activation of the AKT and mTOR pathway."
30662561
OTUB2 decreases the amount of HIF1A.
| 1
OTUB2 decreases the amount of HIF1A. 1 / 1
| 1
reach
"OTUB2 silencing increases the HIF-1alpha protein level and drives ovarian cancer initiation and chemoresistance via activation of its downstream target carbonic anhydrase 9 (CA9)."
38701117
OTUB2 affects FOXM1
| 3 1
OTUB2 binds FOXM1.
| 1 1
OTUB2 binds FOXM1. 2 / 2
| 1 1
sparser
"Mechanistically, OTUB2 could bind FOXM1 and deubiquitinate FOXM1 to stabilize it."
38322554
reach
"Mechanistically, OTUB2 could bind FOXM1 and deubiquitinate FOXM1 to stabilize it."
38322554
OTUB2 deubiquitinates FOXM1.
| 1
OTUB2 deubiquitinates FOXM1. 1 / 1
| 1
reach
"Mechanistically, OTUB2 could bind FOXM1 and deubiquitinate FOXM1 to stabilize it."
38322554
OTUB2 activates FOXM1.
| 1
OTUB2 activates FOXM1. 1 / 1
| 1
reach
"The deubiquitinase OTUB2 promotes cervical cancer growth through stabilizing FOXM1."
38322554
OTUB2 activates Carcinoma, Non-Small-Cell Lung. 4 / 4
| 4
reach
"Moreover, OTUB2 stimulates the Warburg effect and promotes the progression of non-small cell lung cancer (NSCLC) 55."
39776804
reach
"Studies have shown that OTUB2 is abnormally active in a variety of tumor tissues and can promote the development of non-small cell lung cancer [ 13 ], thyroid papillary carcinoma [ 14 ], and liver can[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36858343
reach
"Some researchers have found that OTUB2 promotes the development of breast cancer [5], non-small cell lung cancer [6], thyroid papilloma cancer [7], endometrial cancer [8], and liver cancer [9]."
35850645
reach
"In the context of cancer, OTUB2 has been shown to promote non-small cell lung cancer initiation and progression by stabilizing U2 small nuclear ribonucleoprotein auxiliary factor 2 ( Li et al., 2019 )[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36288705
CircRNA6448-14 affects OTUB2
| 3
CircRNA6448-14 increases the amount of OTUB2. 3 / 3
| 3
reach
"Our findings make a substantial contribution to the understanding of the comparatively sparse circRNA-miRNA-mRNA regulatory network in ESCC.In summary, this study demonstrated that by competitively binding with miR-455-3p, circRNA6448-14 enhanced OTUB2 expression, ESCC glycolysis, and stemness."
38819228
reach
"Additionally, circRNA6448-14 enhanced the expression of OTUB2 by sponging miR-455-3p."
38819228
reach
"Finally, we revealed that circRNA6448-14 promoted OTUB2 expression and enhanced ESCC glycolysis and stemness by competitively binding to miR-455-3p."
38819228
Benzo[a]pyrene affects OTUB2
3 |
Benzo[a]pyrene increases the amount of OTUB2.
2 |
Benzo[a]pyrene increases the amount of OTUB2. 2 / 2
2 |
ctd
No evidence text available
21632981
ctd
No evidence text available
20106945
Benzo[a]pyrene methylates OTUB2.
1 |
Benzo[a]pyrene methylates OTUB2. 1 / 1
1 |
ctd
No evidence text available
27901495
TAFAZZIN affects OTUB2
| 3
reach
"TIMER database (http://timer.cistrome.org) and the Gene Expression Profiling Interactive Analysis (GEPIA) database (http://gepia.cancer-pku.cn/) were used to search the expression of OTUB2 in esophageal cancer; the GeneMANIA database (http://genemania.org/) was used to search the interaction between OTUB2 and YAP1/TAZ (WWTR1:TAZ also known as WWTR1)."
35850645
reach
"OTUB2 can both bind and deubiquitinate and thereby stabilize YAP and TAZ, particularly in cancer cells expressing oncogenic KRAS."
30472188
reach
"OTUB2 can bind and stabilize YAP1/TAZ through ubiquitination, and has a certain positive regulatory effect on YAP1/TAZ."
35850645
RBM15 affects OTUB2
| 3
RBM15 methylates OTUB2.
| 1
RBM15 leads to the methylation of OTUB2. 1 / 1
| 1
reach
"Similarly, in cervical cancer, RBM15 inhibition reduces m6A methylation of OTUB2, leading to the inactivation of the AKT/mTOR pathway, which in turn decreases cell proliferation and metastasis capacity (Song and Wu 2023)."
39716068
RBM15 increases the amount of OTUB2.
| 1
RBM15 increases the amount of OTUB2. 1 / 1
| 1
reach
"Mechanistically, m 6 A RNA immunoprecipitation (Me-RIP) results showed that RBM15 inhibition reduced the m 6 A methylation level of OTUB2 in CC cells, leading to the decline of OTUB2 expression."
37334762
RBM15 decreases the amount of OTUB2.
| 1
RBM15 decreases the amount of OTUB2. 1 / 1
| 1
reach
"Silencing RBM15 has been shown to suppress the malignant properties of CC cells by inhibiting the JAK-STAT signalling pathway and reducing OTUB2 expression (Refs 47, 48, 50)."
39377535
OTUB2-IN-1 affects OTUB2
| 3
OTUB2-IN-1 inhibits OTUB2.
| 2
OTUB2-IN-1 inhibits OTUB2. 2 / 2
| 2
reach
"In addition, OTUB2 inhibition by OTUB2-IN-1 attenuated calcium deposition and osteogenic reprogramming in VSMCs compared with VSMCs treated with the vehicle (Figure S3C-D)."
39776804
reach
"We also injected mice intraperitoneally with OTUB2-IN-1, a specific inhibitor of OTUB2, which was recently identified as able to block the deubiquitinase activity of OTUB2 but did not affect its stability (Figure S2K) 32."
39776804
OTUB2-IN-1 binds OTUB2.
| 1
OTUB2-IN-1 binds OTUB2. 1 / 1
| 1
reach
"Surface plasmon resonance (SPR) assays gave a dissociation constant (K ) value of approximately 12 μM for OTUB2-IN-1 binding to OTUB2 (Fig. 9e)."
38167274
OTUB2 affects translation
| 3
OTUB2 activates translation.
| 2
OTUB2 activates translation. 2 / 2
| 2
reach
"Deletion of OTU2 in yeast also decreased translation, supporting a generally conserved function for OTUD6 ."
39127721
reach
"It has been proposed that Rps7A must be de‐ubiquitinated by Otu2 to enable translation re‐initiation (Ikeuchi et al., 2023; Takehara et al., 2021)."
38009591
OTUB2 inhibits translation.
| 1
OTUB2 inhibits translation. 1 / 1
| 1
reach
"These results suggest that the deletion of Otu2 does not cause abortive translation."
33665564
OTUB2 activates signal transduction.
| 2
reach
"Inhibition of OTUB2 promotes apoptosis and attenuates proliferation and metastasis of CC cells by downregulating the AKT/mTOR signalling pathway (Ref."
39377535
reach
"showed that inhibiting OTUB2 can suppress the growth of colorectal cancer cells by modulating the β-catenin signaling pathway."
39210373
OTUB2 inhibits signal transduction.
| 1
OTUB2 inhibits signal transduction. 1 / 1
| 1
reach
"Inhibition of OTUB2 promotes apoptosis and attenuates proliferation and metastasis of CC cells by downregulating the AKT/mTOR signalling pathway (Ref."
39377535
OTUB2 affects glucose
| 3
OTUB2 activates glucose. 3 / 3
| 3
reach
"Conversely, OTUB2 overexpression substantially enhanced glycolytic capability, glucose uptake and extracellular lactate production in XL-2 and H292 cells."
30662561
reach
"As expected, we verified that OTUB2 overexpression increased ECAR, glucose uptake, and lactate production, while knockdown of OTUB2 impaired the aerobic glycolytic phenotype in different NSCLC cell lines."
30662561
reach
"Moreover, OTUB2 depletion reduces glucose consumption, lactate production, and cellular ATP production."
34671086
OTUB2 activates cell differentiation. 3 / 3
| 3
reach
"Thus, these data suggest that OTUB2 promotes the osteogenic differentiation of VSMCs."
39776804
reach
"YAP knockdown or inhibition effectively antagonized the OTUB2-mediated increase in osteogenic differentiation (Figure 4I, 4K and Figure S5E)."
39776804
reach
"In this study, we revealed that OTUB2 promoted VSMC osteogenic differentiation and aggravated VC both in vivo and in vitro."
39776804
reach
"We showed that OTUB2 prevents cancer stemness via elevated OXPHOS and subsequently increased PS synthesis."
36288705
reach
"Furthermore, treatment of cells with the Ca 2+ channel inhibitor ruthenium red completely abolished the elevated PS synthesis triggered by OTUB2 or CALML3 overexpression ( Figure S3 H), proving the cr[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36288705
reach
"In ESCC, DNA hypermethylation of otubain 2 (OTUB2) has been found to induce tumor initiation and chemoresistance by regulating biosynthesis of phosphatidylserine."
38989149
OTUB2 affects UIMC1
| 3
OTUB2 inhibits UIMC1. 3 / 3
| 3
reach
"OTUB2 enables the initiation of HR by suppressing the excessive accumulation of 53BP1 and RAP80 in an early phase of the DDR [XREF_BIBR, XREF_BIBR]."
30831436
reach
"Thus, the RNF8-RNF168 axis primarily suppresses HR and promotes non-HR-type DSB repair, e.g. NHEJ, and OTUB2 enables the initiation of HR by suppressing the excessive accumulation of 53BP1 and RAP80 in an early phase of the DDR."
26983989
reach
"Taking these findings together, we propose a model whereby OTUB2 inhibits excessive DSB-end protection and allows the initiation of HR by properly regulating the accumulation of RAP80 and 53BP1 at DSB[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24560272
OTUB2 affects UBE2N
1 | 2
OTUB2 inhibits UBE2N.
| 2
OTUB2 inhibits UBE2N. 2 / 2
| 2
reach
"Interestingly, the corresponding residue is a glutamic acid in OTUB2, which lacks an N-terminal arm and does not inhibit UBC13 4."
22367539
reach
"These residues are important for OTUB1 inhibition of E2 activity 4 and are absent in OTUB2, which does not inhibit UBC13 4."
22367539
OTUB2 binds UBE2N.
1 |
OTUB2 binds UBE2N. 1 / 1
1 |
biogrid
No evidence text available
20725033
OTUB2 affects TP53BP1
| 3
OTUB2 inhibits TP53BP1. 3 / 3
| 3
reach
"Thus, the RNF8-RNF168 axis primarily suppresses HR and promotes non-HR-type DSB repair, e.g. NHEJ, and OTUB2 enables the initiation of HR by suppressing the excessive accumulation of 53BP1 and RAP80 in an early phase of the DDR."
26983989
reach
"Taking these findings together, we propose a model whereby OTUB2 inhibits excessive DSB-end protection and allows the initiation of HR by properly regulating the accumulation of RAP80 and 53BP1 at DSB[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24560272
reach
"OTUB2 enables the initiation of HR by suppressing the excessive accumulation of 53BP1 and RAP80 in an early phase of the DDR [XREF_BIBR, XREF_BIBR]."
30831436
OTUB2 affects Stroke
| 3
OTUB2 activates Stroke. 3 / 3
| 3
reach
"Consistently, inhibition of OTUB2 with the small-molecule inhibitor LN5P45 attenuates ischemic stroke injury in mice and reduces neuronal death in human brain organoids after oxygen-glucose deprivation."
40021931
reach
"Furthermore, pharmacological inhibition of OTUB2 attenuated ischemic stroke injury in mice and neuronal death in human brain organoids."
40021931
reach
"However, after middle cerebral artery occlusion (MCAO), the infarct volume in Otub2 mice was significantly smaller than that of Otub2 mice (Fig. 1E,F), indicating that OTUB2 deficiency attenuates ischemic stroke injury."
40021931
OTUB2 affects Stomach Neoplasms
| 3
OTUB2 activates Stomach Neoplasms.
| 2
OTUB2 activates Stomach Neoplasms. 2 / 2
| 2
reach
"38 In the most recent studies, Ouyang et al investigated the mechanisms by which OTUB2 regulates KRT80 stability and thereby promotes proliferation in GC."
37211956
reach
"Knockdown of OTUB2 inhibited the proliferative capacity of GC cells in vitro and in vivo, although the proliferative capacity was restored upon re-supplementation with KRT80."
35110531
OTUB2 binds Stomach Neoplasms. 1 / 1
| 1
reach
"Poor prognosis of patients with GC was revealed to correlate with high expression of OTUB1-isoform 2 (105); the association between OTUB2 and GC remains to be further studied."
31897112
OTUB2 affects RPS7
| 3
OTUB2 deubiquitinates RPS7. 3 / 3
| 3
reach
"Consistent with our findings, the yeast ortholog of OTUD6, OTU2, deubiquitinates yeast RPS7/eS7A on the 40 S ribosomal subunit ."
39127721
reach
"Otu2 deubiquitinates eS7 in order to promote dissociation of the small ribosomal subunit from the mRNA upon completion of translation (129)."
34391779
reach
"In actively translating 80S ribosomes the ribosomal protein eS7 of the 40S subunit is monoubiquitinated by the E3 ligase Not4 and deubiquitinated by Otu2 upon ribosomal subunit recycling."
37169754
OTUB2 affects OTUB2
| 3
OTUB2 decreases the amount of OTUB2.
| 2
OTUB2 decreases the amount of OTUB2. 2 / 2
| 2
reach
"Cell lines with the highest expression of OTUB2 were transfected with lentivirus to knockdown OTUB2 levels."
35850645
reach
"Western blotting was used to detect the expression of OTUB2 protein in three esophageal squamous cell carcinoma cell lines, and the cell line with the highest expression of OTUB2 was selected for lentiviral transfection to knockdown OTUB2 expression."
35850645
OTUB2 inhibits OTUB2.
| 1
OTUB2 inhibits OTUB2. 1 / 1
| 1
reach
"We first used western blotting to detect OTUB2 expression in three ESCC lines, the cell lines with the highest expression of OTUB2 were selected for lentivirus transfection to knockdown OTUB2, and the sequences with the highest knockdown efficiency were selected for subsequent molecular experiments and cell function studies.Target sequence of shRNA: Western Blotting."
35850645
OTUB2 affects Interferon
| 2 1
OTUB2 inhibits Interferon.
| 1 1
OTUB2 inhibits Interferon. 2 / 2
| 1 1
sparser
"Like A20 and OTUD1, otubain 2 (OTUB2) is a DUB of the ovarian tumour protease subfamily. xref Recent studies have found that OTUB2 regulates tumourigenesis and/or progression of multiple cancers. xref , xref , xref For example, OTUB2 deubiquitinates and stabilises U2AF2 and thereby promotes tumourigenesis of non‐small cell lung cancer. xref Besides, OTUB2 promotes breast cancer metastasis by deubiquitinating and activating YAP/TAZ. xref OTUB2 has also been shown to inhibit antitumour immunity by disrupting the ubiquitination and degradation of PD‐L1 on tumour cells. xref In sharp contrast, OTUB2 inhibits tumourigenesis and progression of tongue and oesophageal squamous cell carcinoma by mediating the deubiquitination and activation of STAT1. xref Upon virus infection, OTUB2 inhibits type I IFN production by deubiquitinating TRAF3 and TRAF6, resulting in impaired cellular antiviral response. xref Moreover, OTUB2 has also been shown to fine‐tune DNA repair by suppressing RNF8‐mediated ubiquitination in response to DNA double‐strand breaks. xref However, the pathophysiological function of OTUB2 in intestinal inflammation remains unknown."
39358938
reach
"These findings suggest that OTUB1 and OTUB2 negatively regulate virus triggered type I IFN induction and cellular antiviral response by deubiquitinating TRAF3 and -6."
19996094
OTUB2 decreases the amount of Interferon.
| 1
OTUB2 decreases the amount of Interferon. 1 / 1
| 1
reach
"It is worth noting that OTUB1 and OTUB2 negatively regulate the expression of Ifnβ induced by the VISA-mediated pathway, but not the TBK1-mediated pathway [51]."
37632103
OTUB2 affects IRF3
| 2
OTUB2 inhibits IRF3. 2 / 3
| 2
reach
"Overexpression of OTUB1 and OTUB2 inhibited virus induced activation of IRF3 and NF-kappaB, transcription of the IFNB1 gene as well as cellular antiviral response, whereas knockdown of OTUB1 and OTUB2 had opposite effects."
19996094
reach
"[172] Because various components are involved in virus induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG-I-, MDA5-, and MAVS mediated but not TBK1- and IRF3 mediated signaling."
33511009
OTUB2 affects HIF1
| 3
OTUB2 decreases the amount of HIF1.
| 2
OTUB2 decreases the amount of HIF1. 2 / 2
| 2
reach
"Western blotting indicated that overexpression of OTUB2 and SNX29P2 reduced the protein expression levels of HIF-1α and CA9 under normoxic conditions, whereas the inactivated OTUB2 mutant did not exert such effects (Fig. 5C)."
38701117
reach
"As expected, overexpression of SNX29P2 inhibited the increases in the expression of HIF-1α and CA9 mediated by OTUB2 silencing under normoxic conditions, but these effects were abrogated under hypoxic conditions (Fig. 5D and SI Appendix, Fig. S5B)."
38701117
OTUB2 increases the amount of HIF1.
| 1
OTUB2 increases the amount of ubiquitinated HIF1. 1 / 1
| 1
reach
"Additionally, ubiquitination assays indicated that overexpression of OTUB2 and SNX29P2 increased the level of ubiquitinated HIF-1α (Fig. 5G)."
38701117
OTUB2 affects GST
| 3
OTUB2 binds GST. 3 / 3
| 3
sparser
"RD21A‐HA‐Ubn, ubiquitinated by PbE3‐2 in Escherichia coli using a previously established protocol, was incubated with GST‐OTU2."
40223806
sparser
"The ubiquitination level of RD21A‐HA‐Ubn was markedly reduced following incubation with GST‐OTU2, whereas no reduction was observed with GST alone."
40223806
sparser
"Incubation of recombinant GST-OTUB2 protein with OTUB2-IN-1 resulted in a significant inhibition of Ub-R110 cleavage by GST-OTUB2 in a dose-dependent manner (Supplementary Fig.  xref ), suggesting that OTUB2-IN-1 can inhibit the hydrolytic activity of recombinant GST-OTUB2 protein toward its substrate Ub-R110 in vitro."
38167274
OTUB2 affects FlaG
| 3
OTUB2 binds FlaG. 3 / 3
| 3
sparser
"Moreover, we found that exogenously expressed FLAG‐OTUB2 could bind with HIS‐MYC‐RIPK2 (Figure  xref ), confirming the direct interaction between the two proteins."
39358938
sparser
"Immunoblot analysis confirmed the successful overexpression of OTU2‐FLAG in both rd21a (lines L4 and L5) and Col‐0 (lines L1 and L2) backgrounds (Figure  xref )."
40223806
sparser
"Besides, we also confirmed the direct interaction between exogenously expressed FLAG-OTUB2 and GFP-RIPK3 by Co-IP (Fig.  xref )."
40021931
OTUB2 affects FAM168A
3 |
FAM168A binds OTUB2. 3 / 3
3 |
biogrid
No evidence text available
21516116
biogrid
No evidence text available
32296183
biogrid
No evidence text available
25416956
OTUB2 affects Death
| 3
OTUB2 activates Death.
| 2
OTUB2 activates Death. 2 / 2
| 2
reach
"Consistently, inhibition of OTUB2 with the small-molecule inhibitor LN5P45 attenuates ischemic stroke injury in mice and reduces neuronal death in human brain organoids after oxygen-glucose deprivation."
40021931
reach
"Considering the high abundance of OTUB2 in neurons, OTUB2 may directly regulate neuronal death in ischemic stroke injury."
40021931
OTUB2 inhibits Death.
| 1
OTUB2 inhibits Death. 1 / 1
| 1
reach
"Importantly, pharmacological inhibition of OTUB2 alleviated ischemic brain injury in mice and reduced oxygen-glucose deprivation-induced neuronal death in human brain organoids."
40021931
OTUB2 affects Carcinogenesis
| 3
OTUB2 inhibits Carcinogenesis.
| 2
OTUB2 inhibits Carcinogenesis. 2 / 2
| 2
reach
"OTUB2 was then ectopically expressed in the human tongue and esophageal SCC cell lines UM1 and KYSE30, and limiting dilution assays showed that elevated OTUB2 expression suppressed tumorigenesis ( Fig[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36288705
reach
"Moreover, limiting dilution assays indicated that CALML3 knockdown abolished the suppression of tumorigenesis by OTUB2 ( Figures 2 F, 2G, and S2 C–S2E)."
36288705
OTUB2 activates Carcinogenesis.
| 1
OTUB2 activates Carcinogenesis. 1 / 1
| 1
reach
"Moreover, OTUB2 stabilizes U2 small nuclear RNA auxiliary factor 2 (U2AF2) and induces carcinogenesis via the AKT/mTOR signaling pathway [185]."
35884607
OTUB2 affects BMP2
| 3
OTUB2 increases the amount of BMP2.
| 2
OTUB2 increases the amount of BMP2. 2 / 2
| 2
reach
"OTUB2 knockdown suppressed the alkaline phosphatase activity and the expression of the common osteogenic markers BMP2 and RUNX2 during osteogenesis of mesenchymal stem cells in response to Shh and Smo agonists, suggesting that OTUB2 may play a role in osteogenic differentiation by regulating Hh signaling [64]."
| PMC
reach
"We also found that OTUB2 knockdown suppressed the ALP activity and the expression of the common markers BMP2 and RUNX2 during osteogenesis of MSCs in response to Shh and Smo agonists, which indicated OTUB2 may have effect on osteogenic differentiation by regulating Hh signaling."
30241937
OTUB2 decreases the amount of BMP2.
| 1
OTUB2 decreases the amount of BMP2. 1 / 1
| 1
reach
"In contrast, OTUB2 deficiency dramatically suppressed VSMC calcification and decreased the expression of RUNX2 and BMP2, and, conversely, increased the expression of α-SMA (Figure 2L-M)."
39776804
L3MBTL1 affects OTUB2
| 3
L3MBTL1 binds OTUB2.
| 2
OTUB2 binds L3MBTL1. 2 / 2
| 2
reach
"Therefore, we focused on L3MBTL1 and asked whether OTUB2 prevented RNF8 mediated ubiquitination of L3MBTL1.First, to confirm whether OTUB2 interacts with L3MBTL1, we performed a coimmunoprecipitation [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24560272
reach
"These data suggest that the interaction between OTUB2 and L3MBTL1 is constitutive rather than DNA damage dependent.Next, we investigated whether OTUB2 could deubiquitinate L3MBTL1 in vivo."
24560272
L3MBTL1 inhibits OTUB2.
| 1
L3MBTL1 inhibits OTUB2. 1 / 1
| 1
reach
"In contrast, when OTUB2 was depleted by siRNA, control shRNA expressing cells and L3MBTL1 specific shRNA expressing cells exhibited similar frequencies of cells with large 53BP1 foci."
24560272
GST affects OTUB2
| 3
OTUB2 binds GST. 3 / 3
| 3
sparser
"RD21A‐HA‐Ubn, ubiquitinated by PbE3‐2 in Escherichia coli using a previously established protocol, was incubated with GST‐OTU2."
40223806
sparser
"The ubiquitination level of RD21A‐HA‐Ubn was markedly reduced following incubation with GST‐OTU2, whereas no reduction was observed with GST alone."
40223806
sparser
"Incubation of recombinant GST-OTUB2 protein with OTUB2-IN-1 resulted in a significant inhibition of Ub-R110 cleavage by GST-OTUB2 in a dose-dependent manner (Supplementary Fig.  xref ), suggesting that OTUB2-IN-1 can inhibit the hydrolytic activity of recombinant GST-OTUB2 protein toward its substrate Ub-R110 in vitro."
38167274
FlaG affects OTUB2
| 3
OTUB2 binds FlaG. 3 / 3
| 3
sparser
"Moreover, we found that exogenously expressed FLAG‐OTUB2 could bind with HIS‐MYC‐RIPK2 (Figure  xref ), confirming the direct interaction between the two proteins."
39358938
sparser
"Immunoblot analysis confirmed the successful overexpression of OTU2‐FLAG in both rd21a (lines L4 and L5) and Col‐0 (lines L1 and L2) backgrounds (Figure  xref )."
40223806
sparser
"Besides, we also confirmed the direct interaction between exogenously expressed FLAG-OTUB2 and GFP-RIPK3 by Co-IP (Fig.  xref )."
40021931
FAM168A affects OTUB2
3 |
FAM168A binds OTUB2. 3 / 3
3 |
biogrid
No evidence text available
21516116
biogrid
No evidence text available
32296183
biogrid
No evidence text available
25416956
(+)-JQ1 compound affects OTUB2
3 |
(+)-JQ1 compound decreases the amount of OTUB2. 3 / 3
3 |
ctd
No evidence text available
27432991
ctd
No evidence text available
26752646
ctd
No evidence text available
25307878
Thioacetamide affects OTUB2
2 |
Thioacetamide decreases the amount of OTUB2. 2 / 2
2 |
ctd
No evidence text available
34492290
ctd
No evidence text available
23411599
Silicon dioxide affects OTUB2
2 |
Silicon dioxide increases the amount of OTUB2. 2 / 2
2 |
ctd
No evidence text available
25351596
ctd
No evidence text available
25895662
MiR-455-3p affects OTUB2
| 2
MiR-455-3p increases the amount of OTUB2. 2 / 2
| 2
reach
"In conclusion, circRNA6448-14 promoted the expression of OTUB2 by sponge adsorption of miR-455-3p."
38819228
reach
"In conclusion, circRNA6448-14 sponged miR-455-3p, which in turn promoted OTUB2 expression, thereby enhancing glycolysis and stemness of ESCC cells."
38819228
MiR-378a-3p affects OTUB2
| 2
MiR-378a-3p deubiquitinates OTUB2.
| 1
MiR-378a-3p leads to the deubiquitination of OTUB2. 1 / 1
| 1
reach
"Additionally, miR-378a-3p targeted and downregulated the expression of ubiquitin aldehyde binding 2 (OTUB2), a deubiquitinase associated with TNBC progression."
38702967
MiR-378a-3p decreases the amount of OTUB2.
| 1
MiR-378a-3p decreases the amount of OTUB2. 1 / 1
| 1
reach
"Additionally, miR-378a-3p targeted and downregulated the expression of ubiquitin aldehyde binding 2 (OTUB2), a deubiquitinase associated with TNBC progression."
38702967
Hsa-mir-4279 affects OTUB2
2 |
Hsa-mir-4279 decreases the amount of OTUB2. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
19536157
biopax:mirtarbase
No evidence text available
23824327
Hsa-miR-6856-3p affects OTUB2
2 |
Hsa-miR-6856-3p decreases the amount of OTUB2. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
22012620
biopax:mirtarbase
No evidence text available
23708386
Hsa-miR-629-3p affects OTUB2
2 |
Hsa-miR-629-3p decreases the amount of OTUB2. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
23824327
biopax:mirtarbase
No evidence text available
19536157
Deltamethrin affects OTUB2
2 |
Deltamethrin increases the amount of OTUB2. 2 / 2
2 |
ctd
No evidence text available
37019170
ctd
No evidence text available
34520793
Crocidolite asbestos increases the amount of OTUB2. 2 / 2
2 |
ctd
No evidence text available
25351596
ctd
No evidence text available
29279043
Aflatoxin B1 affects OTUB2
2 |
Aflatoxin B1 increases the amount of OTUB2.
1 |
Aflatoxin B1 increases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
21641981
Aflatoxin B1 decreases the amount of OTUB2.
1 |
Aflatoxin B1 decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
19770486
WWTR1 affects OTUB2
2 |
WWTR1 binds OTUB2. 2 / 2
2 |
biogrid
No evidence text available
30472188
biogrid
No evidence text available
30472188
VHL affects OTUB2
| 1 1
OTUB2 binds VHL. 2 / 2
| 1 1
reach
"Furthermore, in vitro co-IP assays demonstrated that both OTUB2 and SNX29P2 directly interact with VHL and that the interaction between OTUB2 and VHL is independent of the enzymatic activity of OTUB2 (Fig. 5 I and J)."
38701117
sparser
"Furthermore, in vitro co-IP assays demonstrated that both OTUB2 and SNX29P2 directly interact with VHL and that the interaction between OTUB2 and VHL is independent of the enzymatic activity of OTUB2 ( xref )."
38701117
UB chains affects OTUB2
| 2
OTUB2 binds UB chains. 2 / 2
| 2
reach
"Among the eleven A. thaliana OTU DUBs examined, we found that OTU2 and OTLD1 bind UB chains with distinct linkage preferences."
24659992
reach
"A. thaliana OTU2 and OTLD1 bind UB chains with distinct linkage preferences."
24659992
U2AF2 affects PGK1
| 2
OTUB2 binds U2AF2 and PGK1. 2 / 2
| 2
sparser
"High expression of OTUB2, U2AF2 and PGK1 is significantly associated with worse prognosis in NSCLC patients."
30662561
sparser
"In addition, our results suggest that high expression of OTUB2, U2AF2 and PGK1 is significantly associated with worse prognosis in NSCLC patients."
30662561
U2AF1 affects OTUB2
| 2
OTUB2 binds U2AF1. 2 / 2
| 2
sparser
"For example, OTUB2 could bind to and deubiquitinate U2AF1 and then promote NSCLC progression via the AKT/mTOR pathway. xref Hyperbaric oxygen therapy and microRNA 101 have also been proven to repress the Warburg effect by HIF‐1α in NSCLC cells. xref , xref However, the inhibition is still weak, and therefore, a deeper understanding of the mechanisms underlying the Warburg effect is essential to intercept the energy supply and consequently inhibit NSCLC proliferation."
39224032
sparser
"In NSCLC, numerous factors have been proven to be related to the Warburg effect: OTUB2 could bind to and deubiquitinate U2AF1 and consequently promote NSCLC progression, xref and α‐Hederin could inhibit glycolysis in A549 and H460 cells by activating SIRT6. xref Our previous study showed that AMPK could be located on the mitochondria, and this mitoAMPK could inhibit the Warburg effect."
39224032
TRIM8 affects OTUB2
2 |
OTUB2 binds TRIM8. 2 / 2
2 |
biogrid
No evidence text available
23105109
biogrid
No evidence text available
32296183
TRIM54 affects OTUB2
2 |
TRIM54 binds OTUB2. 2 / 2
2 |
biogrid
No evidence text available
25416956
biogrid
No evidence text available
22626734
TP53BP2 affects OTUB2
2 |
TP53BP2 binds OTUB2. 2 / 2
2 |
biogrid
No evidence text available
32296183
biogrid
No evidence text available
25416956
SENP1 affects OTUB2
1 | 1
SENP1 desumoylates OTUB2.
| 1
SENP1 leads to the desumoylation of OTUB2. 1 / 1
| 1
reach
"Moreover, Myc-SUMO3 transfection resulted in OTUB2 poly-SUMOylation, which was significantly decreased by the SUMO-specific protease SENP1 (Figure S6B)."
39776804
SENP1 binds OTUB2.
1 |
SENP1 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
30472188
Raloxifene Hydrochloride decreases the amount of OTUB2. 2 / 2
2 |
ctd
No evidence text available
33269387
ctd
No evidence text available
19059307
RIPK2 affects OTUB2
| 2
OTUB2 binds RIPK2. 2 / 2
| 2
sparser
"RIPK2 was detected in the immunocomplex harvested from BMDMs with anti‐OTUB2 antibody (Figure  xref ), showing that RIPK2 interacts with OTUB2."
39358938
sparser
"To determine the mechanism how OTUB2 stabilises RIPK2, we then examined whether OTUB2 directly interacted with RIPK2."
39358938
RFP affects OTUB2
| 2
OTUB2 binds RFP. 2 / 2
| 2
sparser
"Co‐immunoprecipitation followed by immunoblotting demonstrated that the overall ubiquitination levels remained unchanged when RFP‐OTU1 or RFP‐OTU2 variants were co‐expressed (Figure  xref ; Figure  xref )."
39642157
sparser
"Co‐expression of RFP‐OTU1 or RFP‐OTU2 did not affect the levels of SP‐SUBEX‐C57Y‐GFP protein (Figure  xref ) or lead to the accumulation of SP‐RFP‐SUBEX‐C57Y‐NG11 in the cytosol or nucleus (Figure  xref )."
39642157
REL affects OTUB2
2 |
REL binds OTUB2. 2 / 2
2 |
biogrid
No evidence text available
32296183
biogrid
No evidence text available
25416956
RAS affects OTUB2
| 2
RAS sumoylates OTUB2. 2 / 2
| 2
reach
"Therefore, our observations suggest that EGF and RAS activation might be able to regulate YAP/TAZ through SUMOylating OTUB2."
30472188
reach
"Thus, these clinical data support our model that EGF signaling or RAS activation stimulates OTUB2 SUMOylation and thereby stabilizes YAP/TAZ, which enhances cancer stemness and metastasis ( Figure 7 K[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
POLH affects OTUB2
| 1 1
OTUB2 binds POLH. 2 / 2
| 1 1
sparser
"OTU2 has been previously linked to DNA damage response due to an increase in its protein level upon MMS-induced DNA damage. xref In another study, knockout of OTU2 in yeast cells led to an increased expression of a number of DNA repair proteins. xref In addition, a negative genetic interaction between OTU2 and RAD30, which encodes the translesion DNA synthesis (TLS) polymerase η in yeast, was also reported. xref Our result suggested a potential connection of OTU2 to DNA damage response, particularly PCNA deubiquitination."
30429995
reach
"XREF_BIBR In addition, a negative genetic interaction between OTU2 and RAD30, which encodes the translesion DNA synthesis (TLS) polymerase eta in yeast, was also reported."
30429995
PKM2/PI3K/AKT affects OTUB2
| 2
PKM2/PI3K/AKT increases the amount of OTUB2. 2 / 2
| 2
reach
"Overexpression of OTUB2 could promote glycolysis and induce proliferation, migration, and invasion of EC cells, while inhibition of the PKM2/PI3K/AKT signaling pathway significantly reversed the oncogenic effects of OTUB2 overexpression on EC cells [15]."
37478120
reach
"Importantly, inhibition of the PKM2/PI3K/AKT signaling pathway significantly reversed the promoting effect of OTUB2 overexpression on EC."
36316812
PJA1 affects OTUB2
2 |
PJA1 binds OTUB2. 2 / 2
2 |
biogrid
No evidence text available
35611163
biogrid
No evidence text available
22626734
PIAS3 affects OTUB2
1 | 1
PIAS3 sumoylates OTUB2.
| 1
PIAS3 leads to the sumoylation of OTUB2. 1 / 1
| 1
reach
"Indeed, co-expression of Flag-OTUB2 and Myc-SUMO3 resulted in OTUB2 poly-SUMoylation, which could be strongly enhanced by co-expression of PIAS3 ( Figure 4 B) and decreased by SENP1 ( Figure 4 C)."
30472188
PIAS3 binds OTUB2.
1 |
OTUB2 binds PIAS3. 1 / 1
1 |
biogrid
No evidence text available
30472188
PGK1 affects U2AF2
| 2
OTUB2 binds U2AF2 and PGK1. 2 / 2
| 2
sparser
"High expression of OTUB2, U2AF2 and PGK1 is significantly associated with worse prognosis in NSCLC patients."
30662561
sparser
"In addition, our results suggest that high expression of OTUB2, U2AF2 and PGK1 is significantly associated with worse prognosis in NSCLC patients."
30662561
OTUB2 affects calcium(2+)
| 2
OTUB2 increases the amount of calcium(2+).
| 1
OTUB2 increases the amount of calcium(2+). 1 / 1
| 1
reach
"Mechanistically, we found that the OTUB2/CALML3 axis increased intracellular Ca 2+ levels, OXPHOS, and glycerophospholipid synthesis by affecting membrane ion channels."
36288705
OTUB2 activates calcium(2+).
| 1
OTUB2 activates calcium(2+). 1 / 1
| 1
reach
"In addition, OTUB2 inhibition by OTUB2-IN-1 attenuated calcium deposition and osteogenic reprogramming in VSMCs compared with VSMCs treated with the vehicle (Figure S3C-D)."
39776804
OTUB2 affects ZEB1
| 2
OTUB2 inhibits ZEB1.
| 1
OTUB2 inhibits ZEB1. 1 / 1
| 1
reach
"Silencing OTUB2 induced decreases in ZEB1 and CTNNB1, and CTNNB1 overexpression markedly reversed the change in ZEB1 expression ( Fig. 5 D)."
36858343
OTUB2 increases the amount of ZEB1.
| 1
OTUB2 increases the amount of ZEB1. 1 / 1
| 1
reach
"The results showed that silencing OTUB2 decreased ZEB1 and N-cadherin expression and increased E-cadherin expression, and these effects were markedly reversed by the overexpression of ZEB1 in iCCA cel[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36858343
OTUB2 affects WWTR1
2 |
WWTR1 binds OTUB2. 2 / 2
2 |
biogrid
No evidence text available
30472188
biogrid
No evidence text available
30472188
OTUB2 affects VHL
| 1 1
OTUB2 binds VHL. 2 / 2
| 1 1
reach
"Furthermore, in vitro co-IP assays demonstrated that both OTUB2 and SNX29P2 directly interact with VHL and that the interaction between OTUB2 and VHL is independent of the enzymatic activity of OTUB2 (Fig. 5 I and J)."
38701117
sparser
"Furthermore, in vitro co-IP assays demonstrated that both OTUB2 and SNX29P2 directly interact with VHL and that the interaction between OTUB2 and VHL is independent of the enzymatic activity of OTUB2 ( xref )."
38701117
OTUB2 affects UB chains
| 2
OTUB2 binds UB chains. 2 / 2
| 2
reach
"Among the eleven A. thaliana OTU DUBs examined, we found that OTU2 and OTLD1 bind UB chains with distinct linkage preferences."
24659992
reach
"A. thaliana OTU2 and OTLD1 bind UB chains with distinct linkage preferences."
24659992
OTUB2 affects U2AF1
| 2
OTUB2 binds U2AF1. 2 / 2
| 2
sparser
"For example, OTUB2 could bind to and deubiquitinate U2AF1 and then promote NSCLC progression via the AKT/mTOR pathway. xref Hyperbaric oxygen therapy and microRNA 101 have also been proven to repress the Warburg effect by HIF‐1α in NSCLC cells. xref , xref However, the inhibition is still weak, and therefore, a deeper understanding of the mechanisms underlying the Warburg effect is essential to intercept the energy supply and consequently inhibit NSCLC proliferation."
39224032
sparser
"In NSCLC, numerous factors have been proven to be related to the Warburg effect: OTUB2 could bind to and deubiquitinate U2AF1 and consequently promote NSCLC progression, xref and α‐Hederin could inhibit glycolysis in A549 and H460 cells by activating SIRT6. xref Our previous study showed that AMPK could be located on the mitochondria, and this mitoAMPK could inhibit the Warburg effect."
39224032
OTUB2 affects TRIM8
2 |
OTUB2 binds TRIM8. 2 / 2
2 |
biogrid
No evidence text available
23105109
biogrid
No evidence text available
32296183
OTUB2 affects TRIM54
2 |
TRIM54 binds OTUB2. 2 / 2
2 |
biogrid
No evidence text available
25416956
biogrid
No evidence text available
22626734
OTUB2 affects TP53BP2
2 |
TP53BP2 binds OTUB2. 2 / 2
2 |
biogrid
No evidence text available
32296183
biogrid
No evidence text available
25416956
OTUB2 affects SNX29P2
| 2
OTUB2 deubiquitinates SNX29P2. 2 / 2
| 2
reach
"OTUB2 Deubiquitinates and Stabilizes SNX29P2.."
38701117
reach
"Finally, the direct deubiquitination of SNX29P2 by OTUB2 was validated by an in vitro deubiquitination assay (Fig. 3J)."
38701117
OTUB2 affects RUNX2
| 2
OTUB2 increases the amount of RUNX2. 2 / 2
| 2
reach
"In contrast, OTUB2 deficiency dramatically suppressed VSMC calcification and decreased the expression of RUNX2 and BMP2, and, conversely, increased the expression of α-SMA (Figure 2L-M)."
39776804
reach
"We also found that OTUB2 knockdown suppressed the ALP activity and the expression of the common markers BMP2 and RUNX2 during osteogenesis of MSCs in response to Shh and Smo agonists, which indicated OTUB2 may have effect on osteogenic differentiation by regulating Hh signaling."
30241937
OTUB2 affects RFP
| 2
OTUB2 binds RFP. 2 / 2
| 2
sparser
"Co‐immunoprecipitation followed by immunoblotting demonstrated that the overall ubiquitination levels remained unchanged when RFP‐OTU1 or RFP‐OTU2 variants were co‐expressed (Figure  xref ; Figure  xref )."
39642157
sparser
"Co‐expression of RFP‐OTU1 or RFP‐OTU2 did not affect the levels of SP‐SUBEX‐C57Y‐GFP protein (Figure  xref ) or lead to the accumulation of SP‐RFP‐SUBEX‐C57Y‐NG11 in the cytosol or nucleus (Figure  xref )."
39642157
OTUB2 affects REL
2 |
REL binds OTUB2. 2 / 2
2 |
biogrid
No evidence text available
32296183
biogrid
No evidence text available
25416956
OTUB2 affects POLH
| 1 1
OTUB2 binds POLH. 2 / 2
| 1 1
sparser
"OTU2 has been previously linked to DNA damage response due to an increase in its protein level upon MMS-induced DNA damage. xref In another study, knockout of OTU2 in yeast cells led to an increased expression of a number of DNA repair proteins. xref In addition, a negative genetic interaction between OTU2 and RAD30, which encodes the translesion DNA synthesis (TLS) polymerase η in yeast, was also reported. xref Our result suggested a potential connection of OTU2 to DNA damage response, particularly PCNA deubiquitination."
30429995
reach
"XREF_BIBR In addition, a negative genetic interaction between OTU2 and RAD30, which encodes the translesion DNA synthesis (TLS) polymerase eta in yeast, was also reported."
30429995
OTUB2 affects PGK1, and U2AF2
| 2
OTUB2 binds U2AF2 and PGK1. 2 / 2
| 2
sparser
"High expression of OTUB2, U2AF2 and PGK1 is significantly associated with worse prognosis in NSCLC patients."
30662561
sparser
"In addition, our results suggest that high expression of OTUB2, U2AF2 and PGK1 is significantly associated with worse prognosis in NSCLC patients."
30662561
OTUB2 affects PGAM1
| 1 1
OTUB2 increases the amount of PGAM1.
| 1
Modified OTUB2 increases the amount of PGAM1. 1 / 1
| 1
reach
"Overexpression of OTUB2 upregulated the expression of PFKL and PGK1 in H292 cells and upregulated the expression of HK2, PFKL, PGK1, and PGAM1 in XL-2 cells."
30662561
OTUB2 binds PGAM1.
| 1
PGAM1 binds OTUB2. 1 / 1
| 1
sparser
"UBE2S was found to be overexpressed in GBM cells, where it interacts with PGAM1 and OTUB2 to inhibit PGAM1 degradation via K48-linked deubiquitylation."
39904430
OTUB2 affects OTU
| 2
OTUB2 binds OTU. 1 / 1
| 1
reach
"The network included many proteins, sphingomyelin phosphodiesterase 3 (SMPD3), ubiquitin-conjugating enzyme E2 N (UBE2N), and OTU deubiquitinase ubiquitin aldehyde binding 2 (OTUB2) proteins mainly pa[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
37532135
OTUB2 binds sumoylated OTU. 1 / 1
| 1
reach
"Additionally, Josephin domain-containing protein 2 (JOSD2) and poly-SUMOylated OTU deubiquitinase ubiquitin aldehyde binding 2 (OTUB2) deubiquitinate and stabilize YAP/TAZ [41, 42]."
37743467
OTUB2 affects NMRAL1
2 |
OTUB2 binds NMRAL1. 2 / 2
2 |
biogrid
No evidence text available
31796584
biogrid
No evidence text available
24763515
OTUB2 affects Mice
| 2
OTUB2 activates Mice. 2 / 2
| 2
reach
"Furthermore, in vivo assays show that knockout of OTUB2 inhibits tumor growth in mice."
34671086
reach
"Consistently, inhibition of OTUB2 with the small-molecule inhibitor LN5P45 attenuates ischemic stroke injury in mice and reduces neuronal death in human brain organoids after oxygen-glucose deprivation."
40021931
OTUB2 affects MLKL
| 2
OTUB2 phosphorylates MLKL.
| 1
OTUB2 leads to the phosphorylation of MLKL. 1 / 1
| 1
reach
"Although RIPK1 phosphorylation was not changed, OTUB2 deficiency significantly impaired the phosphorylation of RIPK3 and MLKL (Fig. 3A–D)."
40021931
OTUB2 increases the amount of MLKL.
| 1
OTUB2 increases the amount of MLKL. 1 / 1
| 1
reach
"Besides, OTUB2 deficiency significantly reduced the levels of phosphorylated RIPK3 and MLKL in primary neurons after OGD (Fig. 6C–F), showing that OTUB2 increases neuronal necroptosis after ischemia."
40021931
OTUB2 affects MAVS
1 | 1
OTUB2 inhibits MAVS.
| 1
OTUB2 inhibits MAVS. 1 / 1
| 1
reach
"[172] Because various components are involved in virus induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG-I-, MDA5-, and MAVS mediated but not TBK1- and IRF3 mediated signaling."
33511009
OTUB2 binds MAVS.
1 |
OTUB2 binds MAVS. 1 / 1
1 |
biogrid
No evidence text available
19996094
OTUB2 affects MAGEA11
1 1 |
MAGEA11 binds OTUB2. 2 / 2
1 1 |
biogrid
No evidence text available
16189514
hprd
No evidence text available
16189514
OTUB2 affects Kr
| 2
Kr binds OTUB2. 2 / 2
| 2
sparser
"OTUB2-WT expression increased spontaneous lung metastasis without affecting primary tumor growth, whereas expression of OTUB2-CS or OTUB2-KR had no significant effects ( Figure 5 E–5H)."
30472188
sparser
"H&E and immunohistochemistry (IHC) staining indicated enhanced YAP/TAZ levels in the OTUB2-WT group, but not in the OTUB2-CS and OTUB2-KR groups ( Figure 5 H)."
30472188
OTUB2 affects IFN-I
| 2
OTUB2 inhibits IFN-I.
| 1
OTUB2 inhibits IFN-I. 1 / 1
| 1
reach
"Notably, UCHL1, OTUB1, OTUB2, OTUD5, USP25, MYSM1, and MCPIP1 (Figure 3A) negatively regulate virus-induced IFN-I production and antiviral activities by cleaving K63-linked or other types of polyubiquitin chains from TRAF3 or TRAF6."
34707613
OTUB2 activates IFN-I.
| 1
OTUB2 activates IFN-I. 1 / 1
| 1
reach
"Notably, UCHL1, OTUB1, OTUB2, OTUD5, USP25, MYSM1, and MCPIP1 (Figure 3A) negatively regulate virus-induced IFN-I production and antiviral activities by cleaving K63-linked or other types of polyubiquitin chains from TRAF3 or TRAF6."
34707613
OTUB2 affects Honokiol
| 2
Honokiol binds OTUB2. 2 / 2
| 2
reach
"Bioinformatics analyzed the drug honokiol that bound to OTU deubiquitinase, ubiquitin aldehyde binding 2 (OTUB2)."
38480480
reach
"CETSA confirmed that honokiol could bind to OTUB2."
38480480
OTUB2 affects HYCC1
| 2
OTUB2 activates HYCC1. 2 / 2
| 2
reach
"Functionally, the overexpression of OTUB2 could promote malignant proliferation and metastasis of HCC cells, while knockdown of OTUB2 exerted the opposite results."
35611163
reach
"In conclusion, our study indicated that OTUB2 could promote the malignant proliferation and migration of HCC cells by increasing the stability of PJA1 via deubiquitylation."
35611163
OTUB2 affects HSPA9
2 |
HSPA9 binds OTUB2. 2 / 2
2 |
biogrid
No evidence text available
30021884
biogrid
No evidence text available
34535262
OTUB2 affects Flag
| 2
OTUB2 binds Flag. 2 / 2
| 2
sparser
"Mass spectrometry analysis of Flag-OTUB2 isolated from MDA-MB-231 cells revealed possible SUMOylation at Lys233, which is just before the stop codon ( Figure 4 A; Table S5 )."
30472188
sparser
"Indeed, co-expression of Flag-OTUB2 and Myc-SUMO3 resulted in OTUB2 poly-SUMoylation, which could be strongly enhanced by co-expression of PIAS3 ( Figure 4 B) and decreased by SENP1 ( Figure 4 C)."
30472188
OTUB2 activates DNA-templated transcription. 2 / 2
| 2
reach
"Third, although we found that OTUB2 promotes the transcription of key glycolytic enzymes, including GLUT1, HK2, and PKM2, we cannot exclude the possibility that OTUB2 may regulate other glycolytic enzymes in addition to PFKFB3 to affect VC development."
39776804
reach
"We examined the expression of Hippo target genes following OTUB2 overexpression or depletion and found that OTUB2 depletion inhibited the transcription of Hippo target genes, including CTGF, AREG, and ANKRD1 in VSMCs, whereas the opposite results were observed in the overexpression group (Figure 3I-J)."
39776804
OTUB2 affects DDR
| 2
OTUB2 inhibits DDR. 2 / 2
| 2
reach
"These data indicate that the mechanism by which OTUB2 inhibits the DDR is through its deubiquitination activity, which is different from that of OTUB1.Next, we sought to pinpoint the step of DDR signa[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24560272
reach
"Therefore, we excluded the off-target effects of the siRNA and confirmed that OTUB2 indeed suppressed the DDR in a DUB activity dependent manner."
24560272
OTUB2 affects Cell Survival
| 2
OTUB2 activates Cell Survival. 2 / 2
| 2
reach
"Cell Counting Kit-8 and flow cytometry assay results revealed that overexpression of OTUB2 enhanced cell viability of endometrial cancer cells, while knockdown of OTUB2 inhibited cell viability."
32830515
reach
"Otubain 2 is a novel promoter of beta cell survival as revealed by siRNA high-throughput screens of human pancreatic islets."
23515685
OTUB2 affects CDH1
| 2
OTUB2 increases the amount of CDH1.
| 1
OTUB2 increases the amount of CDH1. 1 / 1
| 1
reach
"The results showed that silencing OTUB2 decreased ZEB1 and N-cadherin expression and increased E-cadherin expression, and these effects were markedly reversed by the overexpression of ZEB1 in iCCA cel[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36858343
OTUB2 decreases the amount of CDH1.
| 1
OTUB2 decreases the amount of CDH1. 1 / 1
| 1
reach
"The results showed that silencing OTUB2 decreased ZEB1 and N-cadherin expression and increased E-cadherin expression, and these effects were markedly reversed by the overexpression of ZEB1 in iCCA cel[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36858343
OTUB2 affects CA9
| 2
OTUB2 decreases the amount of CA9. 2 / 2
| 2
reach
"Western blotting indicated that overexpression of OTUB2 and SNX29P2 reduced the protein expression levels of HIF-1α and CA9 under normoxic conditions, whereas the inactivated OTUB2 mutant did not exert such effects (Fig. 5C)."
38701117
reach
"As expected, overexpression of SNX29P2 inhibited the increases in the expression of HIF-1α and CA9 mediated by OTUB2 silencing under normoxic conditions, but these effects were abrogated under hypoxic conditions (Fig. 5D and SI Appendix, Fig. S5B)."
38701117
OTUB2 affects ARRDC3
2 |
ARRDC3 binds OTUB2. 2 / 2
2 |
biogrid
No evidence text available
25416956
biogrid
No evidence text available
32296183
OTUB2 inhibitors affects OTUB2
| 2
OTUB2 inhibitors leads to the deubiquitination of OTUB2 at position 31. 1 / 1
| 1
reach
"Importantly, LN5P45 as well as other OTUB2 inhibitors strongly induce monoubiquitination of OTUB2 on lysine 31."
37642399
OTUB2 inhibitors leads to the deubiquitination of OTUB2 on lysine. 1 / 1
| 1
reach
"Importantly, LN5P45 as well as other OTUB2 inhibitors strongly induce monoubiquitination of OTUB2 on lysine 31."
37642399
OTU affects OTUB2
| 2
OTUB2 binds OTU. 1 / 1
| 1
reach
"The network included many proteins, sphingomyelin phosphodiesterase 3 (SMPD3), ubiquitin-conjugating enzyme E2 N (UBE2N), and OTU deubiquitinase ubiquitin aldehyde binding 2 (OTUB2) proteins mainly pa[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
37532135
OTUB2 binds sumoylated OTU. 1 / 1
| 1
reach
"Additionally, Josephin domain-containing protein 2 (JOSD2) and poly-SUMOylated OTU deubiquitinase ubiquitin aldehyde binding 2 (OTUB2) deubiquitinate and stabilize YAP/TAZ [41, 42]."
37743467
NMRAL1 affects OTUB2
2 |
OTUB2 binds NMRAL1. 2 / 2
2 |
biogrid
No evidence text available
31796584
biogrid
No evidence text available
24763515
MIR1264 affects OTUB2
2 |
MIR1264 decreases the amount of OTUB2. 2 / 2
2 |
biopax:mirtarbase
No evidence text available
19536157
biopax:mirtarbase
No evidence text available
23824327
MAGEA11 affects OTUB2
1 1 |
MAGEA11 binds OTUB2. 2 / 2
1 1 |
biogrid
No evidence text available
16189514
hprd
No evidence text available
16189514
Kr affects OTUB2
| 2
Kr binds OTUB2. 2 / 2
| 2
sparser
"OTUB2-WT expression increased spontaneous lung metastasis without affecting primary tumor growth, whereas expression of OTUB2-CS or OTUB2-KR had no significant effects ( Figure 5 E–5H)."
30472188
sparser
"H&E and immunohistochemistry (IHC) staining indicated enhanced YAP/TAZ levels in the OTUB2-WT group, but not in the OTUB2-CS and OTUB2-KR groups ( Figure 5 H)."
30472188
Honokiol affects OTUB2
| 2
Honokiol binds OTUB2. 2 / 2
| 2
reach
"Bioinformatics analyzed the drug honokiol that bound to OTU deubiquitinase, ubiquitin aldehyde binding 2 (OTUB2)."
38480480
reach
"CETSA confirmed that honokiol could bind to OTUB2."
38480480
HSPA9 affects OTUB2
2 |
HSPA9 binds OTUB2. 2 / 2
2 |
biogrid
No evidence text available
30021884
biogrid
No evidence text available
34535262
GENEWIZ affects OTUB2
| 2
GENEWIZ activates OTUB2. 2 / 2
| 2
reach
"Human and mouse OTUB2, mouse PD-L1, and HA-Ub were synthesized by GENEWIZ and cloned into the lentiCas9-Puro vector containing a puromycin selection cassette."
38167274
reach
"sgRNA-resistant human and mouse OTUB2 (res OTUB2) constructs were synthesized by GENEWIZ and cloned into the lentiCas9-Blast vector containing a blastcidin selection cassette."
38167274
Flag affects OTUB2
| 2
OTUB2 binds Flag. 2 / 2
| 2
sparser
"Mass spectrometry analysis of Flag-OTUB2 isolated from MDA-MB-231 cells revealed possible SUMOylation at Lys233, which is just before the stop codon ( Figure 4 A; Table S5 )."
30472188
sparser
"Indeed, co-expression of Flag-OTUB2 and Myc-SUMO3 resulted in OTUB2 poly-SUMoylation, which could be strongly enhanced by co-expression of PIAS3 ( Figure 4 B) and decreased by SENP1 ( Figure 4 C)."
30472188
FOXM1 affects OTUB2
| 1 1
OTUB2 binds FOXM1. 2 / 2
| 1 1
sparser
"Mechanistically, OTUB2 could bind FOXM1 and deubiquitinate FOXM1 to stabilize it."
38322554
reach
"Mechanistically, OTUB2 could bind FOXM1 and deubiquitinate FOXM1 to stabilize it."
38322554
CM affects OTUB2
| 1 1
CM leads to the sumoylation of OTUB2. 2 / 2
| 1 1
reach
"In the present study, we discovered that endogenous OTUB2 SUMOylation is promoted by CM, revealing a potential mechanism of YAP activation under calcifying conditions."
39776804
sparser
"In the present study, we discovered that endogenous OTUB2 SUMOylation is promoted by CM, revealing a potential mechanism of YAP activation under calcifying conditions."
39776804
ARRDC3 affects OTUB2
2 |
ARRDC3 binds OTUB2. 2 / 2
2 |
biogrid
No evidence text available
25416956
biogrid
No evidence text available
32296183
17beta-estradiol affects OTUB2
2 |
17beta-estradiol increases the amount of OTUB2. 2 / 2
2 |
ctd
No evidence text available
32145629
ctd
No evidence text available
30165855
Vorinostat affects OTUB2
1 |
Vorinostat decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
27188386
Valdecoxib affects OTUB2
1 |
Valdecoxib decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
24136188
Urethane affects OTUB2
1 |
Urethane decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
28818685
Triptonide affects OTUB2
1 |
Triptonide decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
33045310
Triphenyl phosphate increases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
30589522
Trimellitic anhydride increases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
19042947
Topotecan affects OTUB2
1 |
Topotecan decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
25729387
Titanium dioxide affects OTUB2
1 |
Titanium dioxide methylates OTUB2. 1 / 1
1 |
ctd
No evidence text available
35295148
Thiocyanate affects OTUB2
| 1
Thiocyanate activates OTUB2. 1 / 1
| 1
reach
"To re-examine the ability of OTUB2 to inhibit 53BP1 foci formation, HeLa cells were transiently transfected with Flag-OTUB2 expression vectors, treated with NCS, and then subjected to Flag and 53BP1 i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24560272
Thimerosal affects OTUB2
1 |
Thimerosal decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
27188386
Testosterone affects OTUB2
1 |
Testosterone increases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
26496021
Temozolomide affects OTUB2
1 |
Temozolomide decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
31758290
Tamoxifen affects OTUB2
1 |
Tamoxifen decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
19059307
Sodium dichromate affects OTUB2
1 |
Sodium dichromate decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
25993096
Sodium arsenate affects OTUB2
1 |
Sodium arsenate decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
32525701
Rotenone affects OTUB2
1 |
Rotenone decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
28374803
Quercetin affects OTUB2
1 |
Quercetin increases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
21632981
Pyruvate kinase affects OTUB2
| 1
OTUB2 binds pyruvate kinase. 1 / 1
| 1
sparser
"Mechanistically, OTUB2 directly interacts with pyruvate kinase M2 (PKM2) and inhibits its ubiquitination by blocking the interaction between PKM2 and its ubiquitin E3 ligase Parkin, thereby enhancing PKM2 activity and promoting glycolysis."
34671086
Pirinixic acid affects OTUB2
1 |
Pirinixic acid decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
23811191
Phorbol 13-acetate 12-myristate increases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
25613284
Paracetamol affects OTUB2
1 |
Paracetamol increases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
33387578
Oxaliplatin affects OTUB2
1 |
Oxaliplatin decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
25729387
Ormosil affects OTUB2
1 |
Ormosil increases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
24888373
Orange affects OTUB2
| 1
OTUB2 binds CD274 and orange. 1 / 1
| 1
reach
"We found that the interaction between OTUB2 and PD-L1 (orange signals) mainly colocalized with the ER marker calnexin (Fig. 6b)."
38167274
MiR-29a-3p affects OTUB2
| 1
MiR-29a-3p decreases the amount of OTUB2. 1 / 1
| 1
reach
"Moreover, miR-29a-3p suppresses papillary thyroid carcinoma progression by directly decreasing OTUB2 expression and its associated TRAF6/NF-κB signaling ( Ma and Sun, 2019 )."
33609777
Methapyrilene affects OTUB2
1 |
Methapyrilene methylates OTUB2. 1 / 1
1 |
ctd
No evidence text available
30157460
Methane affects OTUB2
| 1
Methane activates OTUB2. 1 / 1
| 1
reach
"High methane and sulfate supported the growth of anaerobic methane oxidizers and sulfate reducing bacteria as well as the high abundance of Aigarchaeota (OTU2)."
32153535
Metformin affects OTUB2
1 |
Metformin increases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
31324951
Lucanthone affects OTUB2
1 |
Lucanthone increases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
21148553
Ligand affects OTUB2
| 1
Ligand binds OTUB2. 1 / 1
| 1
reach
"The protein RMSD between the apo and the ligand-bound OTUB2 structures was 0."
34071582
Kif6 affects OTUB2
| 1
OTUB2 binds kif6 and K63. 1 / 1
| 1
reach
"We found that OTUB2 specifically interacts with STAT1 and primarily cleaves K6- and K63-linked ubiquitin chains on STAT1."
36288705
Isotretinoin affects OTUB2
1 |
Isotretinoin decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
20436886
Indometacin affects OTUB2
1 |
Indometacin increases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
28628672
Ilf3-a affects OTUB2
| 1
OTUB2 binds ilf3-a. 1 / 1
| 1
sparser
"To explore the role of ribosome-bound Otu2 and Ubp3, and to identify additional factors associated with the respective complexes, we performed a quantitative mass spectrometry-based analysis."
37169754
Icd affects OTUB2
| 1
OTUB2 binds icd. 1 / 1
| 1
sparser
"As OTUB2 interacts with the ICD of PD-L1, we speculated that OTUB2 can remove polyubiquitin chains from the ICD of PD-L1."
38167274
Hsa-mir-4682 affects OTUB2
1 |
Hsa-mir-4682 decreases the amount of OTUB2. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
22012620
Hsa-mir-4424 affects OTUB2
1 |
Hsa-mir-4424 decreases the amount of OTUB2. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
22012620
Hsa-mir-4420 affects OTUB2
1 |
Hsa-mir-4420 decreases the amount of OTUB2. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
22012620
Hsa-mir-4313 affects OTUB2
1 |
Hsa-mir-4313 decreases the amount of OTUB2. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
22012620
Hsa-mir-3943 affects OTUB2
1 |
Hsa-mir-3943 decreases the amount of OTUB2. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
22012620
Hsa-miR-6769a-3p affects OTUB2
1 |
Hsa-miR-6769a-3p decreases the amount of OTUB2. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23708386
Hsa-miR-5687 affects OTUB2
1 |
Hsa-miR-5687 decreases the amount of OTUB2. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23708386
Hsa-miR-4773 affects OTUB2
1 |
Hsa-miR-4773 decreases the amount of OTUB2. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23708386
Hsa-miR-3680-5p affects OTUB2
1 |
Hsa-miR-3680-5p decreases the amount of OTUB2. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
22012620
Hsa-miR-3186-5p affects OTUB2
1 |
Hsa-miR-3186-5p decreases the amount of OTUB2. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23708386
Hsa-miR-215-5p affects OTUB2
1 |
Hsa-miR-215-5p decreases the amount of OTUB2. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
19074876
Hsa-miR-192-5p affects OTUB2
1 |
Hsa-miR-192-5p decreases the amount of OTUB2. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
19074876
Hsa-miR-181b-3p affects OTUB2
1 |
Hsa-miR-181b-3p decreases the amount of OTUB2. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
22012620
Hsa-miR-181b-2-3p affects OTUB2
1 |
Hsa-miR-181b-2-3p decreases the amount of OTUB2. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
22012620
Hsa-miR-125a-5p affects OTUB2
1 |
Hsa-miR-125a-5p decreases the amount of OTUB2. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23622248
Genistein affects OTUB2
1 |
Genistein increases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
20884965
Folic acid affects OTUB2
1 |
Folic acid methylates OTUB2. 1 / 1
1 |
ctd
No evidence text available
20938992
EGFP affects OTUB2
| 1
OTUB2 binds eGFP. 1 / 1
| 1
sparser
"Like the transiently transfected HEK293T cells ( xref ), the eGFP-OTUB2 HeLa clones were treated with increasing concentrations of LN5P45 for 4 h, prior to analysis by Rho-Ub-PA labeling."
37642399
Dorsomorphin affects OTUB2
1 |
Dorsomorphin decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
27188386
Dibutyl phthalate affects OTUB2
1 |
Dibutyl phthalate decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
21266533
Deoxynivalenol affects OTUB2
1 |
Deoxynivalenol increases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
35307453
Cisplatin affects OTUB2
1 |
Cisplatin increases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
27392435
Casticin affects OTUB2
1 |
Casticin decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
28444820
Cadmium dichloride increases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
38174414
Bisphenol F affects OTUB2
1 |
Bisphenol F increases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
28628672
Benzo[e]pyrene affects OTUB2
1 |
Benzo[e]pyrene methylates OTUB2. 1 / 1
1 |
ctd
No evidence text available
30157460
Arsenic atom affects OTUB2
1 |
Arsenic atom decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
32525701
Amino acid affects OTUB2
| 1
Amino acid activates OTUB2. 1 / 1
| 1
reach
"The OTUB2 SUMOylation site is located in the last five amino acid residues, which have been reported to cause OTUB2 self-inhibition ( Balakirev et al., 2003 )."
30472188
Aluminium atom affects OTUB2
1 |
Aluminium atom decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
21298039
Acetamide affects OTUB2
1 |
Acetamide decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
31881176
ZNF211 affects OTUB2
1 |
OTUB2 binds ZNF211. 1 / 1
1 |
biogrid
No evidence text available
30662561
Vanadates affects OTUB2
1 |
Vanadates increases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
22714537
VTP affects OTUB2
| 1
VTP decreases the amount of OTUB2. 1 / 1
| 1
reach
"Consistent with the findings in the VSMC model, the expression levels of PFKFB3 were significantly increased in mouse aortas after OTUB2 overexpression, which was blocked by AAV-shYAP and VTP (Figure 6I)."
39776804
VIM affects OTUB2
1 |
OTUB2 binds VIM. 1 / 1
1 |
biogrid
No evidence text available
30662561
USP32P2 affects OTUB2
1 |
USP32P2 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
19615732
USP21 affects OTUB2
1 |
USP21 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
22626734
UBE2N affects OTUB2
1 |
OTUB2 binds UBE2N. 1 / 1
1 |
biogrid
No evidence text available
20725033
Tobacco Smoke Pollution increases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
33660061
TRRAP affects OTUB2
1 |
TRRAP binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
35906200
TRIM55 affects OTUB2
1 |
TRIM55 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
22626734
TRIM5 affects OTUB2
1 |
OTUB2 binds TRIM5. 1 / 1
1 |
biogrid
No evidence text available
23105109
TRIM39 affects OTUB2
1 |
OTUB2 binds TRIM39. 1 / 1
1 |
biogrid
No evidence text available
23105109
TRIM27 affects OTUB2
1 |
OTUB2 binds TRIM27. 1 / 1
1 |
biogrid
No evidence text available
23105109
TRIM26 affects OTUB2
1 |
OTUB2 binds TRIM26. 1 / 1
1 |
biogrid
No evidence text available
23105109
TRIM25 affects OTUB2
1 |
OTUB2 binds TRIM25. 1 / 1
1 |
biogrid
No evidence text available
23105109
TRIM21 affects OTUB2
1 |
OTUB2 binds TRIM21. 1 / 1
1 |
biogrid
No evidence text available
30662561
TRIM2 affects OTUB2
1 |
OTUB2 binds TRIM2. 1 / 1
1 |
biogrid
No evidence text available
23105109
TRAPPC8 affects OTUB2
1 |
OTUB2 binds TRAPPC8. 1 / 1
1 |
biogrid
No evidence text available
33961781
TRAPPC4 affects OTUB2
1 |
OTUB2 binds TRAPPC4. 1 / 1
1 |
biogrid
No evidence text available
33961781
TRAPPC13 affects OTUB2
1 |
OTUB2 binds TRAPPC13. 1 / 1
1 |
biogrid
No evidence text available
33961781
TRAPPC12 affects OTUB2
1 |
OTUB2 binds TRAPPC12. 1 / 1
1 |
biogrid
No evidence text available
33961781
TRAPPC11 affects OTUB2
1 |
biogrid
No evidence text available
33961781
TRAF6 affects TRAF3
| 1
OTUB1 binds OTUB2, TRAF3, and TRAF6. 1 / 1
| 1
sparser
"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63‐linked polyubiquitin chains. [ xref ] Because various components are involved in virus‐induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG‐I‐, MDA5‐, and MAVS‐mediated but not TBK1‐ and IRF3‐mediated signaling."
33511009
Stroke affects OTUB2
| 1
Stroke activates OTUB2. 1 / 1
| 1
reach
"These in vitro and in vivo data synergistically demonstrate that OTUB2 enhances ischemic stroke injury by potentiating neuronal necroptosis through RIPK3.Since OTUB2 promoted neuronal necroptosis and genetic deletion of OTUB2 ameliorated ischemic stroke injury, we further investigated whether inhibition of OTUB2 with inhibitors could protect mice from ischemic stroke."
40021931
Stomach Neoplasms affects OTUB2
| 1
OTUB2 binds Stomach Neoplasms. 1 / 1
| 1
reach
"Poor prognosis of patients with GC was revealed to correlate with high expression of OTUB1-isoform 2 (105); the association between OTUB2 and GC remains to be further studied."
31897112
Soot affects OTUB2
1 |
Soot decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
26551751
Soman affects OTUB2
1 |
Soman decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
19281266
Smoke affects OTUB2
1 |
Smoke decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
34520756
Saxiphilin affects OTUB2
| 1
Saxiphilin activates OTUB2. 1 / 1
| 1
reach
"FOS increased Ruminococcus2 OTU3 and Lactobacillus OTU37, SAX increased Bacteroides OTU2, and CAX increased Bacteroides OTU11."
28572676
SOX10 affects OTUB2
1 |
OTUB2 binds SOX10. 1 / 1
1 |
biogrid
No evidence text available
30662561
SNAI1 affects OTUB2
1 |
SNAI1 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
31911859
SIM2 affects OTUB2
| 1
SIM2 sumoylates OTUB2. 1 / 1
| 1
reach
"This SIM thus seems to be required for YAP/TAZ-induced transcription.We next examined whether the YAP/TAZ SIM is needed for binding to SUMOylated OTUB2."
30472188
SIAH1 affects OTUB2
1 |
SIAH1 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
25416956
RTCB affects OTUB2
1 |
OTUB2 binds RTCB. 1 / 1
1 |
biogrid
No evidence text available
30662561
RNF126 affects OTUB2
1 |
OTUB2 binds RNF126. 1 / 1
1 |
biogrid
No evidence text available
23105109
RNF123 affects OTUB2
1 |
RNF123 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
29676528
RFFL affects OTUB2
1 |
RFFL binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
22626734
RCC2 affects OTUB2
1 |
OTUB2 binds RCC2. 1 / 1
1 |
biogrid
No evidence text available
30662561
RBCK1 affects OTUB2
1 |
OTUB2 binds RBCK1. 1 / 1
1 |
biogrid
No evidence text available
23105109
Protease affects OTUB2
| 1
Protease leads to the sumoylation of OTUB2. 1 / 1
| 1
reach
"Moreover, Myc-SUMO3 transfection resulted in OTUB2 poly-SUMOylation, which was significantly decreased by the SUMO-specific protease SENP1 (Figure S6B)."
39776804
Polyethylene Glycols increases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
24888373
Particulate Matter decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
38156290
Palm Oil affects OTUB2
1 |
Palm Oil increases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
18042831
PTBP1 affects OTUB2
1 |
OTUB2 binds PTBP1. 1 / 1
1 |
biogrid
No evidence text available
30662561
PRRT2 affects OTUB2
| 1
OTUB2 binds PRRT2. 1 / 1
| 1
reach
"The direct binding of OTUB2 to CTNNB1 in iCCA cells was verified by a Co-IP assay, and overexpression of CTNNB1 in cells with OTUB2 knockdown could rescue ZEB1 expression."
36858343
PRPF19 affects OTUB2
1 |
OTUB2 binds PRPF19. 1 / 1
1 |
biogrid
No evidence text available
30662561
PPP1R9A affects OTUB2
1 |
OTUB2 binds PPP1R9A. 1 / 1
1 |
biogrid
No evidence text available
33961781
POLDIP3 affects OTUB2
1 |
OTUB2 binds POLDIP3. 1 / 1
1 |
biogrid
No evidence text available
30662561
PMEPA1 affects OTUB2
1 |
OTUB2 binds PMEPA1. 1 / 1
1 |
biogrid
No evidence text available
32296183
PHLDA2 affects OTUB2
1 |
OTUB2 binds PHLDA2. 1 / 1
1 |
biogrid
No evidence text available
32296183
PGAM1 affects OTUB2
| 1
PGAM1 binds OTUB2. 1 / 1
| 1
sparser
"UBE2S was found to be overexpressed in GBM cells, where it interacts with PGAM1 and OTUB2 to inhibit PGAM1 degradation via K48-linked deubiquitylation."
39904430
PEMT affects OTUB2
1 |
PEMT binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
33961781
OTUB2 affects β-Catenin
| 1
OTUB2 activates β-Catenin. 1 / 1
| 1
reach
"Inhibition of OTUB2 suppresses colorectal cancer cell growth by regulating β-Catenin signaling."
38058843
OTUB2 affects ubiquitin-proteasome
| 1
OTUB2 inhibits ubiquitin-proteasome. 1 / 1
| 1
reach
"Hence, these results collectively demonstrated that OTUB2 inhibited the ubiquitin-proteasome system-mediated degradation process of SP1 protein, thereby contributing to the stabilization of SP1 protein expression levels."
39210373
OTUB2 affects tumour gastric cancer
| 1
OTUB2 activates tumour gastric cancer. 1 / 1
| 1
eidos
"Correction : OTUB2 regulates KRT80 stability via deubiquitination and promotes tumour proliferation in gastric cancer ."
35440577
OTUB2 affects rps7-A
| 1
OTUB2 ubiquitinates rps7-A. 1 / 1
| 1
sparser
"It has been proposed that Rps7A must be de‐ubiquitinated by Otu2 to enable translation re‐initiation (Ikeuchi et al.,  xref ; Takehara et al.,  xref )."
38009591
OTUB2 affects replication
| 1
OTUB2 inhibits replication. 1 / 1
| 1
sparser
"Knockdown of OTUB1 and OTUB2 inhibited vesicular stomatitis virus (VSV) replication."
23151130
OTUB2 activates regulation of cell population proliferation. 1 / 1
| 1
reach
"In our current study, TRAF6 and phosphorylated AKT expression were repressed after OTUB2 knockdown, which suggested that AKT signaling might be associated with the regulation of cell proliferation and migration mediated by OTUB2 in TNBC.The approval of bortezomib for treating multiple myeloma has confirmed the proteasomes as a valid target for anti-cancer therapy [49]."
40296903
OTUB2 affects receptor-interacting protein kinase 3
| 1
OTUB2 increases the amount of receptor-interacting protein kinase 3. 1 / 1
| 1
reach
"OTUB2 enhances neuronal necroptosis, a predominant form of cell death after ischemic stroke, by maintaining the protein levels of receptor-interacting protein kinase 3 (RIPK3)."
40021931
OTUB2 affects pyruvate kinase
| 1
OTUB2 binds pyruvate kinase. 1 / 1
| 1
sparser
"Mechanistically, OTUB2 directly interacts with pyruvate kinase M2 (PKM2) and inhibits its ubiquitination by blocking the interaction between PKM2 and its ubiquitin E3 ligase Parkin, thereby enhancing PKM2 activity and promoting glycolysis."
34671086
OTUB2 affects polyubiquitin chains
| 1
OTUB2 activates polyubiquitin chains. 1 / 1
| 1
reach
"Notably, UCHL1, OTUB1, OTUB2, OTUD5, USP25, MYSM1, and MCPIP1 (Figure 3A) negatively regulate virus-induced IFN-I production and antiviral activities by cleaving K63-linked or other types of polyubiquitin chains from TRAF3 or TRAF6."
34707613
OTUB2 affects pH reduction
| 1
OTUB2 activates pH reduction. 1 / 1
| 1
reach
"By contrast, OTUB2 knockdown suppressed the O 2 consumption rate (OCR) but increased the extracellular acidification rate (ECAR) ( Figures 3 K, 3L, and S3 G)."
36288705
OTUB2 affects oxaliplatin
| 1
OTUB2 activates oxaliplatin. 1 / 1
| 1
reach
"The results revealed that knockdown or overexpression of OTUB2 significantly enhanced or weakened the inhibitory effect of oxaliplatin on colon cancer cell proliferation (Fig. 2I), while simultaneously augmenting or diminishing its promoting effect on apoptosis induction in colon cancer cells (Fig. 2J)."
39210373
OTUB2 affects orange
| 1
OTUB2 binds CD274 and orange. 1 / 1
| 1
reach
"We found that the interaction between OTUB2 and PD-L1 (orange signals) mainly colocalized with the ER marker calnexin (Fig. 6b)."
38167274
OTUB2 affects nuclear factor-kappaB
| 1
OTUB2 activates nuclear factor-kappaB. 1 / 1
| 1
reach
"OTUB2 knockdown increased caspase-3/7 activity in MIN6 cells and primary human islets and inhibited insulin secretion and increased nuclear factor-kappaB (NF-kappaB) activity both under basal conditions and following cytokine treatment."
23515685
OTUB2 affects non-small cell lung cancer
| 1
OTUB2 activates non-small cell lung cancer. 1 / 1
| 1
reach
"OTUB2 can promote tumorigenic progression of non-small cell lung cancer cells through deubiquitination of U2AF2, stimulation of the Warburg effect, and activation of AKT/mTOR signaling."
37642399
OTUB2 affects mineralization
| 1
OTUB2 activates mineralization. 1 / 1
| 1
reach
"We observed that the increased VSMC mineralization induced by OTUB2 overexpression was significantly abrogated following additional treatment with 3PO and PFK158 (Figure 7C-F)."
39776804
OTUB2 affects ligand
| 1
Ligand binds OTUB2. 1 / 1
| 1
reach
"The protein RMSD between the apo and the ligand-bound OTUB2 structures was 0."
34071582
OTUB2 affects kif6
| 1
OTUB2 binds kif6 and K63. 1 / 1
| 1
reach
"We found that OTUB2 specifically interacts with STAT1 and primarily cleaves K6- and K63-linked ubiquitin chains on STAT1."
36288705
OTUB2 affects inulin
| 1
OTUB2 activates inulin. 1 / 1
| 1
reach
"As shown in Additional file 2: Figure S1, OTU2 were rapidly increased after starting inulin feeding and showed significant compositional increment after 2 weeks of continuous inulin feeding (p values < 4E−02, Tukey’s HSD test)."
31969191
OTUB2 inhibits inflammatory response. 1 / 1
| 1
reach
"Consistent with this possibility, in depth taxonomic analysis of the 16S rDNA dataset revealed that OTU2, OTU6, and OTU24 decreased in their relative abundance with co-housing, indicating that these bacterial species might have promoted skin inflammation in ft/ft mice."
30240702
OTUB2 affects immune response
| 1
OTUB2 inhibits immune response. 1 / 1
| 1
reach
"These results indicate that depletion of OTUB2 enhances antitumor immunity by regulating PD-L1 abundance and activating CTLs."
38167274
OTUB2 affects ilf3-a
| 1
OTUB2 binds ilf3-a. 1 / 1
| 1
sparser
"To explore the role of ribosome-bound Otu2 and Ubp3, and to identify additional factors associated with the respective complexes, we performed a quantitative mass spectrometry-based analysis."
37169754
OTUB2 affects icd
| 1
OTUB2 binds icd. 1 / 1
| 1
sparser
"As OTUB2 interacts with the ICD of PD-L1, we speculated that OTUB2 can remove polyubiquitin chains from the ICD of PD-L1."
38167274
OTUB2 affects glucose consumption
| 1
OTUB2 activates glucose consumption. 1 / 1
| 1
eidos
"Moreover , OTUB2 depletion reduces glucose consumption , lactate production , and cellular ATP production ."
34671086
OTUB2 activates evasion of host immune response. 1 / 1
| 1
reach
"Therefore, whether OTUB2-mediated immune evasion involves other immune-related genes, was not a focus in this study and should be further investigated."
38167274
OTUB2 inhibits endoplasmic reticulum. 1 / 1
| 1
reach
"OTUB2 mediates ER-dependent degradation of PD-L1."
38167274
OTUB2 affects eS7A
| 1
OTUB2 deubiquitinates eS7A. 1 / 1
| 1
reach
"Otu2 and Ubp3 deubiquitinate eS7A in the distinct ribosome complexes."
33665564
OTUB2 affects eGFP
| 1
OTUB2 binds eGFP. 1 / 1
| 1
sparser
"Like the transiently transfected HEK293T cells ( xref ), the eGFP-OTUB2 HeLa clones were treated with increasing concentrations of LN5P45 for 4 h, prior to analysis by Rho-Ub-PA labeling."
37642399
reach
"Some researchers have found that OTUB2 promotes the development of breast cancer [5], non-small cell lung cancer [6], thyroid papilloma cancer [7], endometrial cancer [8], and liver cancer [9]."
35850645
OTUB2 affects circRNA6448-14
| 1
OTUB2 inhibits circRNA6448-14. 1 / 1
| 1
reach
"Overexpression of OTUB2 or silencing miR-455-3p reversed the inhibitory effect of knockdown of circRNA6448-14 on ESCC glycolysis and stemness.Conclusion: This research demonstrated that the circRNA6448-14/miR-455-3p/OTUB2 axis induced the glycolysis and stemness of ESCC cells."
38819228
OTUB2 affects cellular ATP
| 1
OTUB2 activates cellular ATP. 1 / 1
| 1
eidos
"Moreover , OTUB2 depletion reduces glucose consumption , lactate production , and cellular ATP production ."
34671086
OTUB2 affects cell
| 1
OTUB2 activates cell. 1 / 1
| 1
eidos
"In addition , OTUB2 inhibition deactivated the AKT / mTOR signaling in CC cells ."
37334762
OTUB2 affects apoptotic process
| 1
reach
"As indicated by CCK-8, Transwell, and flow cytometry results, OTUB2 silencing attenuated proliferative and metastatic capacities of CC cells but promoted CC cell apoptosis."
37334762
OTUB2 affects activation
| 1
OTUB2 inhibits activation. 1 / 1
| 1
sparser
"Overexpression of OTUB1 and OTUB2 inhibited virus-induced activation of IRF3 and NF-kappaB, transcription of the IFNB1 gene as well as cellular antiviral response, whereas knockdown of OTUB1 and OTUB2 had opposite effects."
19996094
OTUB2 affects ZNF211
1 |
OTUB2 binds ZNF211. 1 / 1
1 |
biogrid
No evidence text available
30662561
OTUB2 affects YAP/TAZ.62
| 1
OTUB2 activates YAP/TAZ.62. 1 / 1
| 1
reach
"Recently, OTUB2 has been shown to bind directly to and activate YAP/TAZ.62 For this interaction to occur, OTUB2 must be sumoylated."
31832513
OTUB2 affects VIM
1 |
OTUB2 binds VIM. 1 / 1
1 |
biogrid
No evidence text available
30662561
OTUB2 affects Ubiquitination
| 1
OTUB2 inhibits Ubiquitination. 1 / 1
| 1
eidos
"Mechanistically , OTUB2 directly interacts with pyruvate kinase M2 ( PKM2 ) and inhibits its ubiquitination by blocking the interaction between PKM2 and its ubiquitin E3 ligase Parkin , thereby enhancing PKM2 activity and promoting glycolysis ."
34671086
OTUB2 affects Ub-R110
| 1
OTUB2 inhibits Ub-R110. 1 / 1
| 1
reach
"Incubation of recombinant GST-OTUB2 protein with OTUB2-IN-1 resulted in a significant inhibition of Ub-R110 cleavage by GST-OTUB2 in a dose-dependent manner (Supplementary Fig. 19b−d), suggesting that OTUB2-IN-1 can inhibit the hydrolytic activity of recombinant GST-OTUB2 protein toward its substrate Ub-R110 in vitro."
38167274
OTUB2 affects USP32P2
1 |
USP32P2 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
19615732
OTUB2 affects USP21
1 |
USP21 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
22626734
OTUB2 affects U2 small nuclear ribonucleoprotein auxiliary factor 2
| 1
OTUB2 activates U2 small nuclear ribonucleoprotein auxiliary factor 2. 1 / 1
| 1
reach
"In the context of cancer, OTUB2 has been shown to promote non-small cell lung cancer initiation and progression by stabilizing U2 small nuclear ribonucleoprotein auxiliary factor 2 ( Li et al., 2019 )[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36288705
OTUB2 affects TRRAP
1 |
TRRAP binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
35906200
OTUB2 affects TRIM55
1 |
TRIM55 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
22626734
OTUB2 affects TRIM5
1 |
OTUB2 binds TRIM5. 1 / 1
1 |
biogrid
No evidence text available
23105109
OTUB2 affects TRIM39
1 |
OTUB2 binds TRIM39. 1 / 1
1 |
biogrid
No evidence text available
23105109
OTUB2 affects TRIM27
1 |
OTUB2 binds TRIM27. 1 / 1
1 |
biogrid
No evidence text available
23105109
OTUB2 affects TRIM26
1 |
OTUB2 binds TRIM26. 1 / 1
1 |
biogrid
No evidence text available
23105109
OTUB2 affects TRIM25
1 |
OTUB2 binds TRIM25. 1 / 1
1 |
biogrid
No evidence text available
23105109
OTUB2 affects TRIM21
1 |
OTUB2 binds TRIM21. 1 / 1
1 |
biogrid
No evidence text available
30662561
OTUB2 affects TRIM2
1 |
OTUB2 binds TRIM2. 1 / 1
1 |
biogrid
No evidence text available
23105109
OTUB2 affects TRAPPC8
1 |
OTUB2 binds TRAPPC8. 1 / 1
1 |
biogrid
No evidence text available
33961781
OTUB2 affects TRAPPC4
1 |
OTUB2 binds TRAPPC4. 1 / 1
1 |
biogrid
No evidence text available
33961781
OTUB2 affects TRAPPC13
1 |
OTUB2 binds TRAPPC13. 1 / 1
1 |
biogrid
No evidence text available
33961781
OTUB2 affects TRAPPC12
1 |
OTUB2 binds TRAPPC12. 1 / 1
1 |
biogrid
No evidence text available
33961781
OTUB2 affects TRAPPC11
1 |
biogrid
No evidence text available
33961781
OTUB2 affects TBK1
| 1
OTUB2 inhibits TBK1. 1 / 1
| 1
reach
"[172] Because various components are involved in virus induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG-I-, MDA5-, and MAVS mediated but not TBK1- and IRF3 mediated signaling."
33511009
OTUB2 affects SOX10
1 |
OTUB2 binds SOX10. 1 / 1
1 |
biogrid
No evidence text available
30662561
OTUB2 affects SNAI1
1 |
SNAI1 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
31911859
OTUB2 affects SLC2A1
| 1
OTUB2 activates SLC2A1. 1 / 1
| 1
reach
"Interestingly, our RT-qPCR results confirmed that OTUB2 overexpression increased the transcript levels of various glycolytic enzymes in VSMCs, including GLUT1, HK2, PKM2, and PFKFB3."
39776804
OTUB2 affects SIAH1
1 |
SIAH1 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
25416956
OTUB2 affects SI
| 1
OTUB2 inhibits SI. 1 / 1
| 1
reach
"Overexpression of OTUB2 in ES-2 and A2780 cells significantly reduced cell proliferation (Fig. 2F and SI Appendix, Fig. S2 E and G)."
38701117
OTUB2 affects SERPINB3
| 1
OTUB2 inhibits SERPINB3. 1 / 1
| 1
reach
"Notably, although the incidence of ESCC gradually increased with time, there was no obvious difference between the numbers of tumor nodules seen in the tongues at 24 and 32 weeks, which may be due to [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36288705
OTUB2 affects SENP1
1 |
SENP1 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
30472188
OTUB2 affects RTCB
1 |
OTUB2 binds RTCB. 1 / 1
1 |
biogrid
No evidence text available
30662561
OTUB2 affects RNF168
| 1
OTUB2 inhibits RNF168. 1 / 1
| 1
reach
"On the other hand, we also found 13 DUBs that were recruited to DNA damage sites but gave only marginal DSB repair defects upon siRNA depletion, including OTUB1, a negative regulator of the UBE2N (UBC13) ubiquitin E2 enzyme 24, USP44 that is reported to antagonize RNF168 dependent ubiquitylation 25, and OTUB2 that functions in repair-pathway choice 26 (XREF_FIG, XREF_FIG, and XREF_FIG), suggesting that some of the additional DUBs we identified might be negative DDR regulators and/or be involved in repair-pathway choice."
25194926
OTUB2 affects RNF126
1 |
OTUB2 binds RNF126. 1 / 1
1 |
biogrid
No evidence text available
23105109
OTUB2 affects RNF123
1 |
RNF123 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
29676528
OTUB2 affects RNA-seq
| 1
OTUB2 activates RNA-seq. 1 / 1
| 1
reach
"Our work provides a new perspective that OTUB2-IN-1, a small-molecule inhibitor that successfully targets OTUB2, may have clinical translational value for VC treatment.We further explored the mechanism by which OTUB2 promotes calcification by performing RNA-seq to identify changes in gene expression in response to OTUB2 overexpression."
39776804
OTUB2 affects RIG-I MDA5 MAVS-mediated TBK1 IRF3-mediated signaling
| 1
OTUB2 inhibits RIG-I MDA5 MAVS-mediated TBK1 IRF3-mediated signaling. 1 / 1
| 1
eidos
"] Because various components are involved in virus-induced signaling , biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG-I - , MDA5 - , and MAVS-mediated but not TBK1 - and IRF3-mediated signaling ."
33511009
OTUB2 affects RFFL
1 |
RFFL binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
22626734
OTUB2 affects RCC2
1 |
OTUB2 binds RCC2. 1 / 1
1 |
biogrid
No evidence text available
30662561
OTUB2 affects RBCK1
1 |
OTUB2 binds RBCK1. 1 / 1
1 |
biogrid
No evidence text available
23105109
OTUB2 affects Protease
| 1
OTUB2 deubiquitinates Protease. 1 / 1
| 1
reach
"A second shared gene of interest is OTU2 that encodes a putative otubain related deubiquitylating protease XREF_BIBR, XREF_BIBR."
24009520
OTUB2 affects Papilloma
| 1
OTUB2 activates Papilloma. 1 / 1
| 1
reach
"Some researchers have found that OTUB2 promotes the development of breast cancer [5], non-small cell lung cancer [6], thyroid papilloma cancer [7], endometrial cancer [8], and liver cancer [9]."
35850645
OTUB2 affects PTBP1
1 |
OTUB2 binds PTBP1. 1 / 1
1 |
biogrid
No evidence text available
30662561
OTUB2 affects PRPF19
1 |
OTUB2 binds PRPF19. 1 / 1
1 |
biogrid
No evidence text available
30662561
OTUB2 affects PPP1R9A
1 |
OTUB2 binds PPP1R9A. 1 / 1
1 |
biogrid
No evidence text available
33961781
OTUB2 affects PPP1CB
| 1
OTUB2 activates PPP1CB. 1 / 1
| 1
reach
"Besides, the OTU33, OTU3, and OTU2 increased in the LP, MP, HP, and HM groups as compared to the CD and HFD groups."
33711371
OTUB2 affects POLDIP3
1 |
OTUB2 binds POLDIP3. 1 / 1
1 |
biogrid
No evidence text available
30662561
OTUB2 affects PMEPA1
1 |
OTUB2 binds PMEPA1. 1 / 1
1 |
biogrid
No evidence text available
32296183
OTUB2 affects PIAS3
1 |
OTUB2 binds PIAS3. 1 / 1
1 |
biogrid
No evidence text available
30472188
OTUB2 affects PI3K
| 1
OTUB2 activates PI3K. 1 / 1
| 1
reach
"Given that OTUB2 promotes gastric cancer growth and proliferation by positively regulating the activation of the PI3K/AKT signaling pathway via KRT80, we believe that KRT80 also has clinical effects similar to OTUB2."
37211956
OTUB2 affects PHLDA2
1 |
OTUB2 binds PHLDA2. 1 / 1
1 |
biogrid
No evidence text available
32296183
OTUB2 affects PFKL
| 1
Modified OTUB2 increases the amount of PFKL. 1 / 1
| 1
reach
"Overexpression of OTUB2 upregulated the expression of PFKL and PGK1 in H292 cells and upregulated the expression of HK2, PFKL, PGK1, and PGAM1 in XL-2 cells."
30662561
OTUB2 affects PEMT
1 |
PEMT binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
33961781
OTUB2 affects PD-L1Δ
| 1
OTUB2 leads to the deubiquitination of PD-L1Δ. 1 / 1
| 1
reach
"In line with the lack of interaction between OTUB2 and PD-L1ΔICD, we observed that compared with full-length PD-L1 (PD-L1 FL), PD-L1ΔICD was barely modified by polyubiquitination, and OTUB2 did not reduce the polyubiquitination of PD-L1ΔICD (Fig. 5e)."
38167274
OTUB2 activates Oxygen Consumption. 1 / 1
| 1
reach
"By contrast, OTUB2 knockdown suppressed the O 2 consumption rate (OCR) but increased the extracellular acidification rate (ECAR) ( Figures 3 K, 3L, and S3 G)."
36288705
OTUB2 affects OTUB2-IN-1
| 1
OTUB2-IN-1 binds OTUB2. 1 / 1
| 1
reach
"Surface plasmon resonance (SPR) assays gave a dissociation constant (K ) value of approximately 12 μM for OTUB2-IN-1 binding to OTUB2 (Fig. 9e)."
38167274
OTUB2 affects NPSR1
1 |
NPSR1 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
33961781
OTUB2 affects NPM1
1 |
OTUB2 binds NPM1. 1 / 1
1 |
biogrid
No evidence text available
34671086
OTUB2 affects NOD2
| 1
OTUB2 activates NOD2. 1 / 1
| 1
reach
"Upon MDP stimulation, OTUB2 promoted NOD2 signaling by stabilizing RIPK2."
39358938
OTUB2 affects NF-kappaB inhibitors
| 1
OTUB2 activates NF-kappaB inhibitors. 1 / 1
| 1
reach
"Additionally, we found that liver cancer cell lines harboring higher OTUB2 expression were more sensitive to NF-kappaB inhibitors, and overexpression of OTUB2 could significantly reduce the antitumor effects of NF-kappaB inhibitors in liver cancer cells."
32003539
OTUB2 affects NEDD8
1 |
NEDD8 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
34642328
OTUB2 affects NCOA5
1 |
OTUB2 binds NCOA5. 1 / 1
1 |
biogrid
No evidence text available
30662561
OTUB2 affects MYH9
1 |
MYH9 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
40437099
OTUB2 affects MPRIP
1 |
OTUB2 binds MPRIP. 1 / 1
1 |
biogrid
No evidence text available
33961781
OTUB2 affects MID2
1 |
MID2 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
25416956
OTUB2 affects MGI.B
| 1
OTUB2 activates MGI.B. 1 / 1
| 1
reach
"MGI.A and MGI.B, which were more abundant in subsurface and mesopelagic layers, were mainly contributed by OTU6 and OTU2, respectively."
29109713
OTUB2 affects MGI.A
| 1
OTUB2 activates MGI.A. 1 / 1
| 1
reach
"MGI.A and MGI.B, which were more abundant in subsurface and mesopelagic layers, were mainly contributed by OTU6 and OTU2, respectively."
29109713
OTUB2 affects MAP1LC3
| 1
OTUB2 leads to the deubiquitination of MAP1LC3. 1 / 1
| 1
reach
"Altogether, these results indicate that OTUB2 decreases LC3 ubiquitylation mediated by TRAF6 and suppresses ubiquitinated LC3-induced CTNNB1 autolysosomal degradation.iCCA, second only to hepatocellul[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36858343
OTUB2 affects LN5P45
| 1
LN5P45 binds OTUB2. 1 / 1
| 1
reach
"For crystallization, the covalent LN5P45-OTUB2 complex was generated by incubating 40 μM purified OTUB2 with a five-fold excess of the inhibitor for 1 h at 37 °C in GF buffer (50 mM Tris pH 7.5, 100 mM NaCl, 2 mM TCEP)."
37642399
OTUB2 affects LMBRD1
1 |
LMBRD1 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
40437099
OTUB2 affects KRT40
1 |
OTUB2 binds KRT40. 1 / 1
1 |
biogrid
No evidence text available
25416956
OTUB2 affects KRT31
1 |
KRT31 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
25416956
OTUB2 affects KDM1A
| 1
OTUB2 increases the amount of KDM1A. 1 / 1
| 1
reach
"Notably, we demonstrated that OTUB2 increased lysine-specific histone demethylase 1A (KDM1A) expression through deubiquitination."
34646768
OTUB2 affects KCTD6
1 |
OTUB2 binds KCTD6. 1 / 1
1 |
biogrid
No evidence text available
33961781
OTUB2 affects K63
| 1
OTUB2 binds kif6 and K63. 1 / 1
| 1
reach
"We found that OTUB2 specifically interacts with STAT1 and primarily cleaves K6- and K63-linked ubiquitin chains on STAT1."
36288705
OTUB2 affects Ischemia
| 1
OTUB2 activates Ischemia. 1 / 1
| 1
reach
"Collectively, these findings show that OTUB2 enhances ischemia-induced neuronal necroptosis by regulating RIPK3 through its DUB activity."
40021931
OTUB2 affects INS
| 1
OTUB2 activates INS. 1 / 1
| 1
reach
"OTUB2 knockdown increased caspase-3/7 activity in MIN6 cells and primary human islets and inhibited insulin secretion and increased nuclear factor-kappaB (NF-kappaB) activity both under basal conditions and following cytokine treatment."
23515685
OTUB2 affects Histone
| 1
OTUB2 leads to the deubiquitination of Histone. 1 / 1
| 1
reach
"However, OTUB2 does not suppress histone ubiquitination induced by RNF168 overexpression [XREF_BIBR]."
26983989
OTUB2 affects Hedgehog
| 1
OTUB2 activates Hedgehog. 1 / 1
| 1
eidos
"( C ) Hedgehog signaling : OTUB2 enhances Hh signaling through deubiquitinating Gli2 ."
36340031
OTUB2 affects HP
| 1
OTUB2 activates HP. 1 / 1
| 1
reach
"Besides, the OTU33, OTU3, and OTU2 increased in the LP, MP, HP, and HM groups as compared to the CD and HFD groups."
33711371
OTUB2 affects HNRNPF
1 |
OTUB2 binds HNRNPF. 1 / 1
1 |
biogrid
No evidence text available
30662561
OTUB2 affects HK2
| 1
Modified OTUB2 increases the amount of HK2. 1 / 1
| 1
reach
"Overexpression of OTUB2 upregulated the expression of PFKL and PGK1 in H292 cells and upregulated the expression of HK2, PFKL, PGK1, and PGAM1 in XL-2 cells."
30662561
OTUB2 affects Glu-Ser
| 1
OTUB2 inhibits Glu-Ser. 1 / 1
| 1
reach
"Rhodococcus sp. OC_3C (same as ES_64F) OTU2 readily degraded ES but not OC."
38010544
OTUB2 affects GTF2I
1 |
OTUB2 binds GTF2I. 1 / 1
1 |
biogrid
No evidence text available
19615732
OTUB2 affects GPBP1
1 |
GPBP1 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
28514442
OTUB2 affects GAPDH
1 |
OTUB2 binds GAPDH. 1 / 1
1 |
biogrid
No evidence text available
30662561
OTUB2 affects ESR1
| 1
OTUB2 activates ESR1. 1 / 1
| 1
reach
"Clearly, the RTP values of compounds 2a and 2c are far greater for the ERbeta mediated response (OTUB2 activation in ERalpha + ERbeta cells) than the ERalpha mediated response (PR activation in ERalpha only cells)."
25559213
OTUB2 affects EEF1A1
1 |
OTUB2 binds EEF1A1. 1 / 1
1 |
biogrid
No evidence text available
30662561
OTUB2 affects ECAR
| 1
OTUB2 activates ECAR. 1 / 1
| 1
reach
"As expected, we verified that OTUB2 overexpression increased ECAR, glucose uptake, and lactate production, while knockdown of OTUB2 impaired the aerobic glycolytic phenotype in different NSCLC cell lines."
30662561
OTUB2 affects E3_Ub_ligase
| 1
OTUB2 binds E3_Ub_ligase. 1 / 1
| 1
reach
"Second, while we have demonstrated that OTUB2 can inhibit K48 ubiquitination-mediated degradation of SP1 and upregulate its expression, it remains unknown whether OTUB2 competitively binds to the ubiquitin or E3 ubiquitin ligase binding site on SP1."
39210373
OTUB2 affects Disease
| 1
OTUB2 activates Disease. 1 / 1
| 1
reach
"OTUB2 is likely to cause cancer and other malignant diseases while maintaining normal human development and physiological function."
35309903
OTUB2 affects DYRK3
| 1
OTUB2 activates DYRK3. 1 / 1
| 1
reach
"Grouper OTUB1 and OTUB2 promote Red-spotted grouper nervous necrosis virus (RGNNV) replication by inhibiting the host innate immune response."
38909637
OTUB2 affects DNA Damage
| 1
OTUB2 inhibits DNA Damage. 1 / 1
| 1
reach
"OTUB2 was recently reported to suppress DNA damage responses through suppression of deubiquitylation of ubiquitylated proteins with RNF8 XREF_BIBR."
27507734
OTUB2 affects DAZAP2
1 |
OTUB2 binds DAZAP2. 1 / 1
1 |
biogrid
No evidence text available
32296183
OTUB2 affects Chemokine
| 1
OTUB2 increases the amount of Chemokine. 1 / 1
| 1
reach
"However, Otub2 and Otub2 microglia produced comparable levels of pro-inflammatory cytokines and chemokines upon stimulation with lipopolysaccharide (LPS) (Appendix Fig. S3A–E)."
40021931
OTUB2 affects Carcinoma
| 1
OTUB2 activates Carcinoma. 1 / 1
| 1
reach
"In oral and esophageal squamous cell carcinomas, OTUB2 activates CALML3 (34), a specific marker of the squamous epithelium (42–44), to exert its tumor-suppressive effects."
38701117
OTUB2 affects CRC
| 1
OTUB2 activates CRC. 1 / 1
| 1
reach
"Here we demonstrate that OTUB2, an OTU deubiquitinase, is upregulated in colorectal cancer (CRC) and exacerbates the progression of CRC through modulating the aerobic glycolysis."
34671086
OTUB2 affects CPSF6
1 |
CPSF6 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
25416956
OTUB2 affects CPLX3
1 |
CPLX3 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
28514442
OTUB2 affects CISH
| 1
OTUB2 inhibits CISH. 1 / 1
| 1
reach
"On the other hand, OTUB2 depletion increased the resistance of KYSE150 and CAL-27 cells to cisplatin treatment, with CIs ranging from 2.31 to 3.23; ectopic CALML3 expression rescued these phenotypes ([MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36288705
OTUB2 affects CDIP1
1 |
CDIP1 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
32296183
OTUB2 affects CDH2
| 1
OTUB2 increases the amount of CDH2. 1 / 1
| 1
reach
"The results showed that silencing OTUB2 decreased ZEB1 and N-cadherin expression and increased E-cadherin expression, and these effects were markedly reversed by the overexpression of ZEB1 in iCCA cel[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36858343
OTUB2 affects CD24
| 1
OTUB2 activates CD24. 1 / 1
| 1
reach
"The increased tumor mammosphere formation and CD44 high /CD24 low population induced by ectopic OTUB2 were significantly reduced upon the pretreatment of the cells with VP ( Figure S3 F), suggesting t[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
OTUB2 affects CCR1
1 |
CCR1 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
33961781
OTUB2 affects BLVRB
| 1
BLVRB binds OTUB2. 1 / 1
| 1
sparser
"PCR and qPCR reactions were performed as described previously ( Westerholm et al., 2016 ) with the following exceptions: 0.5 μL of the forward and the reverse primers (20 μM) except for primer pair OT[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
27423543
OTUB2 affects Akt1
1 |
OTUB2 binds Akt1. 1 / 1
1 |
biogrid
No evidence text available
32133736
OTUB2 affects APP
1 |
OTUB2 binds APP. 1 / 1
1 |
biogrid
No evidence text available
21832049
OTUB2 affects ALDO
| 1
OTUB2 activates ALDO. 1 / 1
| 1
reach
"Analyses using a Seahorse XF96 analyzer revealed that OTUB2 deficiency suppressed glycolytic flux and decreased the production of lactate."
39776804
OTUB2 affects ABCE1
| 1
OTUB2 binds ABCE1. 1 / 1
| 1
sparser
"The interaction of Rli1 with Otu2 was further confirmed by immunoblot analysis using strains endogenously expressing GFP-tagged Rli1 and Otu2-3×Flag ( xref C)."
33665564
OTUB2 affects 8xGTIIC-Luc reporter
| 1
OTUB2 increases the amount of 8xGTIIC-Luc reporter. 1 / 1
| 1
reach
"Depletion of endogenous OTUB2 by two independent small hairpin RNA (shRNA) repressed YAP- and TAZ-induced 8xGTIIC-Luc reporter activity; ectopic expression of OTUB2-WT, but not the inactive CS mutant,[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
OTUB2 affects 4 D
| 1
OTUB2 binds NR4A1 and 4 D. 1 / 1
| 1
reach
"We also observed that OTUB2 also bind to Nur77 ( Fig. 4 D)."
30905540
OTUB1 affects TRAF6
| 1
OTUB1 binds OTUB2, TRAF3, and TRAF6. 1 / 1
| 1
sparser
"Coimmunoprecipitation analyses indicate that OTUB1 and OTUB2 associate with TRAF3 and TRAF6, negatively regulating antiviral responses by deubiquitinating their respective K63‐linked polyubiquitin chains. [ xref ] Because various components are involved in virus‐induced signaling, biochemical assays have demonstrated that OTUB1 and OTUB2 inhibit RIG‐I‐, MDA5‐, and MAVS‐mediated but not TBK1‐ and IRF3‐mediated signaling."
33511009
reach
"Histological analyses not only indicated a significant increase in the number of metastatic lesions but also in the average surface area/intensity of the metastasis produced by OTUB2-expressing cells [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30472188
NR4A1 affects 4 D
| 1
OTUB2 binds NR4A1 and 4 D. 1 / 1
| 1
reach
"We also observed that OTUB2 also bind to Nur77 ( Fig. 4 D)."
30905540
NPSR1 affects OTUB2
1 |
NPSR1 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
33961781
NPM1 affects OTUB2
1 |
OTUB2 binds NPM1. 1 / 1
1 |
biogrid
No evidence text available
34671086
NEDD8 affects OTUB2
1 |
NEDD8 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
34642328
NCOA5 affects OTUB2
1 |
OTUB2 binds NCOA5. 1 / 1
1 |
biogrid
No evidence text available
30662561
N-nitrosodimethylamine decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
25380136
N-methyl-4-phenylpyridinium increases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
28801915
Methylmercury Compounds decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
22129749
MYH9 affects OTUB2
1 |
MYH9 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
40437099
MPRIP affects OTUB2
1 |
OTUB2 binds MPRIP. 1 / 1
1 |
biogrid
No evidence text available
33961781
MID2 affects OTUB2
1 |
MID2 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
25416956
MAVS affects OTUB2
1 |
OTUB2 binds MAVS. 1 / 1
1 |
biogrid
No evidence text available
19996094
LMBRD1 affects OTUB2
1 |
LMBRD1 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
40437099
L-methionine affects OTUB2
1 |
L-methionine methylates OTUB2. 1 / 1
1 |
ctd
No evidence text available
20938992
KRT40 affects OTUB2
1 |
OTUB2 binds KRT40. 1 / 1
1 |
biogrid
No evidence text available
25416956
KRT31 affects OTUB2
1 |
KRT31 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
25416956
KCTD6 affects OTUB2
1 |
OTUB2 binds KCTD6. 1 / 1
1 |
biogrid
No evidence text available
33961781
K63 affects kif6
| 1
OTUB2 binds kif6 and K63. 1 / 1
| 1
reach
"We found that OTUB2 specifically interacts with STAT1 and primarily cleaves K6- and K63-linked ubiquitin chains on STAT1."
36288705
JUN affects OTUB2
1 |
JUN decreases the amount of OTUB2. 1 / 1
1 |
biopax:msigdb
No evidence text available
HNRNPF affects OTUB2
1 |
OTUB2 binds HNRNPF. 1 / 1
1 |
biogrid
No evidence text available
30662561
GTF2I affects OTUB2
1 |
OTUB2 binds GTF2I. 1 / 1
1 |
biogrid
No evidence text available
19615732
GPBP1 affects OTUB2
1 |
GPBP1 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
28514442
GAPDH affects OTUB2
1 |
OTUB2 binds GAPDH. 1 / 1
1 |
biogrid
No evidence text available
30662561
Fig. S6A-C affects OTUB2
| 1
Fig. S6A-C decreases the amount of OTUB2. 1 / 1
| 1
reach
"Conversely, OTUB2 overexpression weakened EMT and migration ability of colon cancer cells but could be restored by GINS1 knockdown (Fig. S6A-C)."
39210373
ESCC affects OTUB2
| 1
ESCC activates OTUB2. 1 / 1
| 1
reach
"When we silenced OTUB2 using lentivirus interference in an ESCC cell line, the progression of ESCC was significantly inhibited."
35850645
EEF1A1 affects OTUB2
1 |
OTUB2 binds EEF1A1. 1 / 1
1 |
biogrid
No evidence text available
30662561
E3_Ub_ligase affects OTUB2
| 1
OTUB2 binds E3_Ub_ligase. 1 / 1
| 1
reach
"Second, while we have demonstrated that OTUB2 can inhibit K48 ubiquitination-mediated degradation of SP1 and upregulate its expression, it remains unknown whether OTUB2 competitively binds to the ubiquitin or E3 ubiquitin ligase binding site on SP1."
39210373
DAZAP2 affects OTUB2
1 |
OTUB2 binds DAZAP2. 1 / 1
1 |
biogrid
No evidence text available
32296183
Cuprizon affects OTUB2
1 |
Cuprizon decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
26577399
CPSF6 affects OTUB2
1 |
CPSF6 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
25416956
CPLX3 affects OTUB2
1 |
CPLX3 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
28514442
CHAF1A affects OTUB2
| 1
CHAF1A activates OTUB2. 1 / 1
| 1
reach
"Notably, maternal Caf diet appeared to prevent a depletion of OTU2 in group CafCaf after the switch to chow, in contrast to the reduction in abundance of this bacterium in group CCaf post‐switch."
36271770
CDIP1 affects OTUB2
1 |
CDIP1 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
32296183
CD274 affects orange
| 1
OTUB2 binds CD274 and orange. 1 / 1
| 1
reach
"We found that the interaction between OTUB2 and PD-L1 (orange signals) mainly colocalized with the ER marker calnexin (Fig. 6b)."
38167274
CCR1 affects OTUB2
1 |
CCR1 binds OTUB2. 1 / 1
1 |
biogrid
No evidence text available
33961781
CALML3 affects OTUB2
| 1
CALML3 activates OTUB2. 1 / 1
| 1
reach
"Further lipidomic analyses indicated that OTUB2/STAT1 promoted phosphatidylserine (PS) synthesis by activating calmodulin-like protein 3 ( CALML3 )."
36288705
CA9 affects OTUB2
| 1
CA9 inhibits OTUB2. 1 / 1
| 1
reach
"Activation of CA9 restores OTUB2-mediated inhibition of glycolysis and tumor growth; thus, CA9 inhibitors might be a promising strategy for ovarian cancer treatment."
38701117
BLVRB affects OTUB2
| 1
BLVRB binds OTUB2. 1 / 1
| 1
sparser
"PCR and qPCR reactions were performed as described previously ( Westerholm et al., 2016 ) with the following exceptions: 0.5 μL of the forward and the reverse primers (20 μM) except for primer pair OT[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
27423543
Akt1 affects OTUB2
1 |
OTUB2 binds Akt1. 1 / 1
1 |
biogrid
No evidence text available
32133736
Air Pollutants affects OTUB2
1 |
Air Pollutants increases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
38156290
ctd
No evidence text available
30157460
APP affects OTUB2
1 |
OTUB2 binds APP. 1 / 1
1 |
biogrid
No evidence text available
21832049
ABCE1 affects OTUB2
| 1
OTUB2 binds ABCE1. 1 / 1
| 1
sparser
"The interaction of Rli1 with Otu2 was further confirmed by immunoblot analysis using strains endogenously expressing GFP-tagged Rli1 and Otu2-3×Flag ( xref C)."
33665564
AAV-shYAP affects OTUB2
| 1
AAV-shYAP decreases the amount of OTUB2. 1 / 1
| 1
reach
"Consistent with the findings in the VSMC model, the expression levels of PFKFB3 were significantly increased in mouse aortas after OTUB2 overexpression, which was blocked by AAV-shYAP and VTP (Figure 6I)."
39776804
4 D affects OTUB2
| 1
OTUB2 binds NR4A1 and 4 D. 1 / 1
| 1
reach
"We also observed that OTUB2 also bind to Nur77 ( Fig. 4 D)."
30905540
2-hydroxypropanoic acid decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
30851411
4,4'-diaminodiphenylmethane decreases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
25380136
3,3',5,5'-tetrabromobisphenol A increases the amount of OTUB2. 1 / 1
1 |
ctd
No evidence text available
25172293