IndraLab
Statements
reach
"As shown in Fig. 2b, both wild-type JOSD2 and its catalytic mutants interact with KRAS, suggesting that the catalytic activity of JOSD2 is not necessary for KRAS binding to JOSD2.In addition, we also observed an interaction between exogenous JOSD2 and endogenous KRAS as well as exogenous KRAS and endogenous JOSD2 (Fig. 2c, d)."
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"To further demonstrate that the interaction between KRAS and JOSD2 is influenced by physiological or pathological conditions, we then introduced EGF and found that EGF stimulation indeed significantly promoted the MAPK signaling pathway (Supplementary Fig. 2f), which is consistent with the previous study ."
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"As shown in Fig. 4q, KRAS mutants significantly upregulated JOSD2 levels, but failed to pose similar effects in CHIP-depleted cells, indicating that KRAS mutants upregulated JOSD2 relying on CHIP.Given that JOSD2 functions as a DUB, we further investigate whether JOSD2 exhibits auto-DUB activity."
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"However, despite the activated state of YAP/TAZ, depletion of JOSD2 still shows more robust anti-tumor effects in KRAS-mutant xenografts compared to the wild-type counterparts, further demonstrating that the growth-inhibitory effect of JOSD2 knockdown depends, at least partially, on the degradation of mutant KRAS.Given that KRAS mutants upregulated JOSD2 levels relying on CHIP, whether CHIP overexpression plays a similar role as JOSD2 shRNA?"
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"By comparing the clinical tumor samples from KRAS-mutant/wild-type CRC patients, in addition to integrating oncogenic mutations (G12C, G12D, G12V, G12A, G12S, G13C, G13D, G13V) into KRAS wild-type cells, our study substantiated the hypothesis that the mutational activation of KRAS robustly augments JOSD2 expression."
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"As shown in Fig. 6e, f and Supplementary Fig. 9a, b, HY041004 remarkably suppressed the cell proliferation and colony formation of HT-29-KRAS in vitro, and the effect of HY041004 on HT-29-KRAS is significantly stronger than that on HT-29-KRAS , whereas KRAS covalent inhibitors MRTX-849 only selectively inhibited KRAS CRC cells (Supplementary Fig. 9b), suggesting the potential of JOSD2 inhibition as the promising pan-KRAS-mutation-targeting strategy."
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"As shown in Fig. 2b, both wild-type JOSD2 and its catalytic mutants interact with KRAS, suggesting that the catalytic activity of JOSD2 is not necessary for KRAS binding to JOSD2.In addition, we also observed an interaction between exogenous JOSD2 and endogenous KRAS as well as exogenous KRAS and endogenous JOSD2 (Fig. 2c, d)."
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"To further demonstrate that the interaction between KRAS and JOSD2 is influenced by physiological or pathological conditions, we then introduced EGF and found that EGF stimulation indeed significantly promoted the MAPK signaling pathway (Supplementary Fig. 2f), which is consistent with the previous study ."
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"As shown in Supplementary Fig. 3i, depletion of JOSD2 significantly downregulated intratumor KRAS levels, indicating JOSD2 inhibition is capable of suppressing KRAS turnover in vitro and in vivo.To further investigate the contribution of JOSD2 in KRAS-mutant CRC growth in preclinical settings, we conducted KRAS-mutant CRC patient-derived cells (PDCs) and patient-derived xenografts (PDX) models (Fig. 3a)."
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"Subsequent in vivo xenografts demonstrated that JOSD2 inhibition dramatically suppressed KRAS-mutant CRC PDXs growth and downregulated intratumor KRAS, p-MEK and p-ERK levels, with inhibition ratio as 73.24% (PDX-1 xenografts) and 81.12% (PDX-2 xenografts) (Fig. 3b–e, Supplementary Fig. 3m and Supplementary Table 2), which is consistent with the results of SW480 and SW620 xenografts.These results collectively demonstrated that JOSD2 plays a crucial role in KRAS-mutant CRC and that targeting JOSD2 significantly suppressed KRAS-mutant CRC growth in vitro and in vivo."
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"Specifically, when JOSD2 removes the polyubiquitin chains from KRAS, the steric hindrance is reduced, thereby promoting the KRAS-RAF1 interaction, which will be further investigated in our future study.Taken together, these data confirmed that JOSD2 positively regulated KRAS abundance and activity in an enzymatic activity-dependent manner."
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"Given that JOSD2 has been shown to reverse the polyubiquitin chains of KRAS mediated by LZTR1, which is reported to promote K48, K63, and K33-linked ubiquitin chains as part of its function as a “RAS killer protein” and JOSD2 also can deubiquitinate K6-linked ubiquitination of LKB1 and affecting its kinase activity , so we next tested the effects of GST-JOSD2 on K6-, K33-, K48-, K63- and K48R-linked ubiquitin chains of KRAS."
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"On this basis, overexpression of JOSD2, not JOSD1, dramatically decreased the polyubiquitin chains of KRAS promoted by LZTR1 and restored the LZTR1-mediated KRAS levels downregulation (Fig. 2k and Supplementary Fig. 2k, l), indicating that JOSD2 reversed the effect of LZTR1-mediated KRAS ubiquitination degradation."
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"Finally, the interaction between endogenous JOSD2 and IMPDH2 in mouse primary bone marrow-derived macrophages (BMDMs) was confirmed by Co-IP assay under physiological conditions, and the interaction between JOSD2 and IMPDH2 was further increased when the BMDMs were challenged by lipopolysaccharide (LPS) (Fig. 5H)."
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"Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-kappaB) and inflammation in macrophages."
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"Furthermore, compared to the wide-type IMPDH2, the ubiquitination level of IMPDH2-K134R mutant was significantly reduced and JOSD2 failed to further deubiquitinate IMPDH2-K134R mutant, indicating that K134 in IMPDH2 is essential for ubiquitination and JOSD2-mediated deubiquitination (Fig. S9B).3.7
JOSD2 inhibits the activity of IMPDH2 to suppress downstream NF-kappaB activation."
JOSD2 affects cell population proliferation
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JOSD2 activates cell population proliferation.
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JOSD2 inhibits cell population proliferation.
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JOSD2 inhibits cell population proliferation. 2 / 2
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"In addition, we transfected β-TRCP and cullin 1, two subunits of E3 ligase SCF into RBE cells, and found that YAP/TAZ protein levels were down-regulated as expected; in the contrast, the exogenous introduction of JOSD2 abrogated SCF -mediated degradation of YAP/TAZ in a deubiquitinase activity-dependent manner (Fig. 2I)."
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"In addition, we transfected β-TRCP and cullin 1, two subunits of E3 ligase SCF into RBE cells, and found that YAP/TAZ protein levels were down-regulated as expected; in the contrast, the exogenous introduction of JOSD2 abrogated SCF -mediated degradation of YAP/TAZ in a deubiquitinase activity-dependent manner (Fig. 2I)."
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"Notably, GST-JOSD2 significantly diminished the kinase activity of LKB1 but showed only slight effect on LKB1-3KR, suggesting that the three lysine residues responsible for K6-linked ubiquitination on LKB1 are critical in mediating JOSD2 modulation on LKB1 kinase activity (Fig. 4e)."
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"These findings not only provide a new inhibitor against DUB(s) with the potential to be developed as a candidate compound for cancer therapy, but also implicated that the pharmacological inhibition of JOSD2 by small molecular compound(s) could reactivate LKB1 by modulating its K6 linkage, thus further verified this newly-established JOSD2-LKB1 axis which was critical for NSCLC proliferation."
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"These findings are consistent with our in vitro finding that JOSD2 negatively regulates LKB1 pathway and promotes NSCLC cell growth dependent of LKB1.These results collectively provided clinical relevance that JOSD2 plays a crucial role in promoting NSCLC cell proliferation through LKB1 kinase activity inhibition."
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"In addition, to better consolidate our conclusion that JOSD2 regulated LKB1 activity by removing K6-ub but not K63-ub, we also investigated the effects of JOSD2 on K63-ub of LKB1, as shown in supplementary Fig. S4f, g, neither overexpression nor depletion of JOSD2 posed effects on LKB1 K63-ub, suggested that as a DUB for LKB1, JOSD2 preferentially cleaved K6 linkage but not K63 linkage.Hence, these results indicated that JOSD2 was a bona fide DUB for LKB1, as JOSD2 bound to LKB1 and removed the K6-linked polyubiquitination on LKB1."
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"Further cellular assays revealed that both HY041004 and HY04071 robustly blocked the loss of K6-linked polyubiquitination on LKB1 caused by JOSD2 (Fig. 7c), suggesting that these two compounds not only inhibit the in vitro deubiquitinating activity of JOSD2, but also efficiently suppress its catalytic activity in the cells."
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"To pinpoint the specific lysine linkage on LKB1 mediated by JOSD2, we performed a cell-based ubiquitination assay using WT-Ub and seven mutant forms of ubiquitin: ubiquitin-K6, ubiquitin-K11, ubiquitin-K27, ubiquitin-K29, ubiquitin-K33, ubiquitin-K48 and ubiquitin-K63, each links to the substrate in a distinctive manner."
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"Finally, the interaction between endogenous JOSD2 and IMPDH2 in mouse primary bone marrow-derived macrophages (BMDMs) was confirmed by Co-IP assay under physiological conditions, and the interaction between JOSD2 and IMPDH2 was further increased when the BMDMs were challenged by lipopolysaccharide (LPS) (Fig. 5H)."
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"Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-kappaB) and inflammation in macrophages."
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"This newly identified catalytic site can serve as a potential target for developing inhibitors against JOSD2 catalytic activity.In attempts to elucidate the underlying mechanisms of tumor-promoting effect of JOSD2, we found that overexpression of JOSD2 removes K6-linked polyubiquitination of LKB1, and the deubiquitination of K6 linkage of LKB1 leads to disruption of LKB1/STRAD/MO25 complex integrity, thus inhibits kinase activity of LKB1 and downstream AMPK signaling pathway, so as to induce cell proliferation."
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"Nonetheless, in LKB1-null cells, silencing JOSD2 still exhibited a certain inhibitory effect on the proliferation, suggesting that other protein substrates in addition to LKB1, might also be involved in JOSD2-driven NSCLC proliferation and cannot be excluded.To further demonstrate that the tumor-promoting effect of JOSD2 depends on LKB1, LKB1-WT and LKB1-3KR were introduced to LKB-null NCI-H460 cells."
JOSD2 affects response to xenobiotic stimulus
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JOSD2 affects glycolytic process
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JOSD2 activates glycolytic process.
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JOSD2 inhibits glycolytic process.
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"Contemporary research has demonstrated that JOSD2 can significantly impact metabolic and neoplastic diseases by modulating several signaling pathways by deubiquitinating different substrate proteins, such as sarcoplasmic/endoplasmic reticulum Ca ATPase 2a (SERCA2a), Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ), catenin beta-1 (CTNNB1), and a metabolic enzyme complex encompassing phosphoglycerate dehydrogenase, phosphofructokinase-1, and aldolase A16, 17, 18, 19."
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"As shown in Fig. 4q, KRAS mutants significantly upregulated JOSD2 levels, but failed to pose similar effects in CHIP-depleted cells, indicating that KRAS mutants upregulated JOSD2 relying on CHIP.Given that JOSD2 functions as a DUB, we further investigate whether JOSD2 exhibits auto-DUB activity."
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"Moreover, CHIP positively regulated the K48-linked polyubiquitination levels of JOSD2 (Fig. 4m, n and Supplementary Fig. 4l–n), indicating CHIP binds to JOSD2 and regulates the latter’s ubiquitination levels.To further demonstrate that CHIP functions as an E3 ligase regulating JOSD2, we next examined the effect of CHIP on JOSD2 protein levels."
JOSD2 affects Cholangiocarcinoma
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"In addition, to better consolidate our conclusion that JOSD2 regulated LKB1 activity by removing K6-ub but not K63-ub, we also investigated the effects of JOSD2 on K63-ub of LKB1, as shown in supplementary Fig. S4f, g, neither overexpression nor depletion of JOSD2 posed effects on LKB1 K63-ub, suggested that as a DUB for LKB1, JOSD2 preferentially cleaved K6 linkage but not K63 linkage.Hence, these results indicated that JOSD2 was a bona fide DUB for LKB1, as JOSD2 bound to LKB1 and removed the K6-linked polyubiquitination on LKB1."
JOSD2 is modified
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JOSD2 affects NSCLC
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JOSD2 activates NSCLC.
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"Nonetheless, in LKB1-null cells, silencing JOSD2 still exhibited a certain inhibitory effect on the proliferation, suggesting that other protein substrates in addition to LKB1, might also be involved in JOSD2-driven NSCLC proliferation and cannot be excluded.To further demonstrate that the tumor-promoting effect of JOSD2 depends on LKB1, LKB1-WT and LKB1-3KR were introduced to LKB-null NCI-H460 cells."
JOSD2 deubiquitinates NSCLC.
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"Similarly, compared with the AAV6-NC group, AAV6-mediated JOSD2 overexpression significantly inhibited DSS-induced colon shortening and colon epithelial damage in mice, as seen in Fig. 8C–F. Moreover, AAV6-mediated JOSD2 overexpression markedly reduced the expression of proinflammatory cytokine and chemokine genes compared with the AAV6-NC-injected group (Fig. 8G)."
JOSD2 affects Leukemia, Myeloid, Acute
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JOSD2 affects Hypertrophy
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JOSD2 inhibits Hypertrophy.
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JOSD2 activates Hypertrophy.
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"Contemporary research has demonstrated that JOSD2 can significantly impact metabolic and neoplastic diseases by modulating several signaling pathways by deubiquitinating different substrate proteins, such as sarcoplasmic/endoplasmic reticulum Ca ATPase 2a (SERCA2a), Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ), catenin beta-1 (CTNNB1), and a metabolic enzyme complex encompassing phosphoglycerate dehydrogenase, phosphofructokinase-1, and aldolase A16, 17, 18, 19."
JOSD2 affects localization
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sparser
"Subsequently, we examined the biological activity of GST-JOSD2/JOSD1 by introducing their co-reported substrate proteins YAP xref , xref , as shown in Supplementary Fig. xref , both GST-JOSD2 and GST-JOSD1 efficiently removing the polyubiquitin chains of YAP, confirming that our purified recombinant protein are biologically active."
sparser
"Given that JOSD2 has been shown to reverse the polyubiquitin chains of KRAS mediated by LZTR1, which is reported to promote K48, K63, and K33-linked ubiquitin chains as part of its function as a “RAS killer protein” and JOSD2 also can deubiquitinate K6-linked ubiquitination of LKB1 and affecting its kinase activity xref , xref , so we next tested the effects of GST-JOSD2 on K6-, K33-, K48-, K63- and K48R-linked ubiquitin chains of KRAS."
sparser
"Subsequently, we examined the biological activity of GST-JOSD2/JOSD1 by introducing their co-reported substrate proteins YAP xref , xref , as shown in Supplementary Fig. xref , both GST-JOSD2 and GST-JOSD1 efficiently removing the polyubiquitin chains of YAP, confirming that our purified recombinant protein are biologically active."
sparser
"Given that JOSD2 has been shown to reverse the polyubiquitin chains of KRAS mediated by LZTR1, which is reported to promote K48, K63, and K33-linked ubiquitin chains as part of its function as a “RAS killer protein” and JOSD2 also can deubiquitinate K6-linked ubiquitination of LKB1 and affecting its kinase activity xref , xref , so we next tested the effects of GST-JOSD2 on K6-, K33-, K48-, K63- and K48R-linked ubiquitin chains of KRAS."
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JOSD2 inhibits epithelial to mesenchymal transition.
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JOSD2 inhibits epithelial to mesenchymal transition. 1 / 1
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"We found that ATXN3 inhibited apoptosis, while JOSD1 and JOSD2 promoted apoptosis, JOSD2 inhibited DNA damage response, JOSD1 and JOSD2 promoted EMT, and JOSD2 suppressed RTK and androgen pathways.Moreover, we used the cBioPortal database to explore the co-expression (Table 3) and mutual exclusion (Table 4) between individual members of the MJDs family."
JOSD2 activates epithelial to mesenchymal transition.
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JOSD2 activates epithelial to mesenchymal transition. 1 / 1
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"We found that ATXN3 inhibited apoptosis, while JOSD1 and JOSD2 promoted apoptosis, JOSD2 inhibited DNA damage response, JOSD1 and JOSD2 promoted EMT, and JOSD2 suppressed RTK and androgen pathways.Moreover, we used the cBioPortal database to explore the co-expression (Table 3) and mutual exclusion (Table 4) between individual members of the MJDs family."
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"Moreover, CHIP positively regulated the K48-linked polyubiquitination levels of JOSD2 (Fig. 4m, n and Supplementary Fig. 4l–n), indicating CHIP binds to JOSD2 and regulates the latter’s ubiquitination levels.To further demonstrate that CHIP functions as an E3 ligase regulating JOSD2, we next examined the effect of CHIP on JOSD2 protein levels."
JOSD2 affects Neoplasm Metastasis
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JOSD2 affects Neoplasm Invasiveness
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"Moreover, a recent report described that R779C, a gain of function mutation of NLRP3, promotes NLRP3 de-ubiquitylation by BRCC3 and JOSD2 to promote NLRP3 activation, which increases the risk of developing Very-early-onset inflammatory bowel disease (VEOIBD), a chronic inflammatory disease of the gastrointestinal tract can happen in early childhood (Zhou et al., 2021)."
JOSD2 binds NLRP3.
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"Together, these findings highlight OTUD6B as a DUB that maintains KIFC1 levels to ensure supernumerary centrosomes remain clustered, allowing cancer cells to avoid mitotic catastrophe and complete cell division.Amongst the 94 DUBs screened, we found that depletion of only OTUD6B or JOSD2 could both reduce cellular KIFC1 levels and increase multipolar spindles in TNBC cells (Figs."
JOSD2 affects ESCC
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JOSD2 affects Cell Survival
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"This provides a strong indication that the observed anti-tumor effects of HY041004 in vivo are indeed mainly through JOSD2 inhibition.Taken together, these data collectively demonstrated depletion of JOSD2 or pharmacological inhibiting JOSD2 significantly suppressed the growth of CRC in vitro and in vivo, especially KRAS-mutant CRC."
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"This provides a strong indication that the observed anti-tumor effects of HY041004 in vivo are indeed mainly through JOSD2 inhibition.Taken together, these data collectively demonstrated depletion of JOSD2 or pharmacological inhibiting JOSD2 significantly suppressed the growth of CRC in vitro and in vivo, especially KRAS-mutant CRC."
JOSD2 affects CRC growth
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HY041004 affects JOSD2
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E3_Ub_ligase affects JOSD2
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E3_Ub_ligase binds JOSD2.
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E3_Ub_ligase binds JOSD2. 1 / 1
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E3_Ub_ligase activates JOSD2.
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E3_Ub_ligase activates JOSD2. 1 / 1
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Pyruvate kinase affects JOSD2
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Isopropyl β-d-thiogalactoside affects JOSD2
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Adeno-associated virus 6 affects JOSD2
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"In order to investigate the therapeutic potential of JOSD2 in colitis, the adeno-associated virus 6 with macrophage-specific CD68 promoter and JOSD2 plasmid (AAV6-JOSD2) was injected in the mice subjected to DSS-induced colitis to achieve the macrophage-specific overexpression of JOSD2 in mice."
STK11 affects K6
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"In addition, to better consolidate our conclusion that JOSD2 regulated LKB1 activity by removing K6-ub but not K63-ub, we also investigated the effects of JOSD2 on K63-ub of LKB1, as shown in supplementary Fig. S4f, g, neither overexpression nor depletion of JOSD2 posed effects on LKB1 K63-ub, suggested that as a DUB for LKB1, JOSD2 preferentially cleaved K6 linkage but not K63 linkage.Hence, these results indicated that JOSD2 was a bona fide DUB for LKB1, as JOSD2 bound to LKB1 and removed the K6-linked polyubiquitination on LKB1."
PR619 affects JOSD2
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"As shown in Supporting Information Fig. S4A, PR619 greatly abolished the deubiquitinating efficiency of JOSD2 on YAP, as indicated by the reversal of loss of poly-ubiquitin chains on YAP in PR619 treated cells.Collectively, these results demonstrate that JOSD2 stabilizes YAP/TAZ through the cleavage of poly-ubiquitin chains from YAP/TAZ, which confirm its regulation on YAP/TAZ as a DUB.3.5
JOSD2 is essential for the growth of CCA xenograft and positively correlated with YAP in CCA patients."
NLRP3 affects JOSD2
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K63 affects JOSD2
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"Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-kappaB) and inflammation in macrophages."
K6 affects STK11
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"In addition, to better consolidate our conclusion that JOSD2 regulated LKB1 activity by removing K6-ub but not K63-ub, we also investigated the effects of JOSD2 on K63-ub of LKB1, as shown in supplementary Fig. S4f, g, neither overexpression nor depletion of JOSD2 posed effects on LKB1 K63-ub, suggested that as a DUB for LKB1, JOSD2 preferentially cleaved K6 linkage but not K63 linkage.Hence, these results indicated that JOSD2 was a bona fide DUB for LKB1, as JOSD2 bound to LKB1 and removed the K6-linked polyubiquitination on LKB1."
JOSD2-LKB1 affects JOSD2
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"The therapeutic potential of this newly identified JOSD2-LKB1 regulatory axis was then verified by both RNA interference and small-molecule inhibitors that abolish DUB activity of JOSD2 and exert potent anticancer activities.JOSD2 belongs to the MJD subfamily of DUB that also includes Ataxin-3, Atanxin-3L and JOSD1."
JOSD2-3KR affects JOSD2
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JOSD2 affects regulation of cell cycle
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JOSD2 inhibits regulation of cell cycle. 1 / 1
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"In addition, we further examined the effects of JOSD2 knockdown on cell cycle and found depletion of JOSD2 significantly induced cell cycle arrest (Supplementary Fig. S8e), moreover, the levels of p-ERK and p-Akt, two classical pathways associated with cell proliferation, were also significantly inhibited (Supplementary Fig. S3c)."
JOSD2 affects pyruvate kinase
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"Furthermore, compared to the wide-type IMPDH2, the ubiquitination level of IMPDH2-K134R mutant was significantly reduced and JOSD2 failed to further deubiquitinate IMPDH2-K134R mutant, indicating that K134 in IMPDH2 is essential for ubiquitination and JOSD2-mediated deubiquitination (Fig. S9B).3.7
JOSD2 inhibits the activity of IMPDH2 to suppress downstream NF-kappaB activation."
JOSD2 affects polyubiquitin chains
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"Given that JOSD2 has been shown to reverse the polyubiquitin chains of KRAS mediated by LZTR1, which is reported to promote K48, K63, and K33-linked ubiquitin chains as part of its function as a “RAS killer protein” and JOSD2 also can deubiquitinate K6-linked ubiquitination of LKB1 and affecting its kinase activity , so we next tested the effects of GST-JOSD2 on K6-, K33-, K48-, K63- and K48R-linked ubiquitin chains of KRAS."
JOSD2 affects phosphofructokinase
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JOSD2 activates phosphofructokinase. 1 / 1
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JOSD2 affects nuclear localization PKM2
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JOSD2 affects glucose metabolic process
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JOSD2 activates glucose metabolic process. 1 / 1
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JOSD2 affects cell death
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JOSD2 activates cell death. 1 / 1
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JOSD2 affects calcium(2+)
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JOSD2 activates calcium(2+). 1 / 1
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JOSD2 affects apoptotic process
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JOSD2 activates apoptotic process. 1 / 1
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"We found that ATXN3 inhibited apoptosis, while JOSD1 and JOSD2 promoted apoptosis, JOSD2 inhibited DNA damage response, JOSD1 and JOSD2 promoted EMT, and JOSD2 suppressed RTK and androgen pathways.Moreover, we used the cBioPortal database to explore the co-expression (Table 3) and mutual exclusion (Table 4) between individual members of the MJDs family."
reach
"We found that ATXN3 inhibited apoptosis, while JOSD1 and JOSD2 promoted apoptosis, JOSD2 inhibited DNA damage response, JOSD1 and JOSD2 promoted EMT, and JOSD2 suppressed RTK and androgen pathways.Moreover, we used the cBioPortal database to explore the co-expression (Table 3) and mutual exclusion (Table 4) between individual members of the MJDs family."
JOSD2 affects YAP TAZ proteasomal
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JOSD2 affects Wnt pathway transduction
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JOSD2 affects TAZ16
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JOSD2 affects SERCA2a
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"We found that ATXN3 inhibited apoptosis, while JOSD1 and JOSD2 promoted apoptosis, JOSD2 inhibited DNA damage response, JOSD1 and JOSD2 promoted EMT, and JOSD2 suppressed RTK and androgen pathways.Moreover, we used the cBioPortal database to explore the co-expression (Table 3) and mutual exclusion (Table 4) between individual members of the MJDs family."
JOSD2 affects PKM2 nuclear localization
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JOSD2 affects NSCLC growth
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JOSD2 affects NLRP3-R779C
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"In addition, we transfected β-TRCP and cullin 1, two subunits of E3 ligase SCF into RBE cells, and found that YAP/TAZ protein levels were down-regulated as expected; in the contrast, the exogenous introduction of JOSD2 abrogated SCF -mediated degradation of YAP/TAZ in a deubiquitinase activity-dependent manner (Fig. 2I)."
JOSD2 affects K63
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"Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-kappaB) and inflammation in macrophages."
reach
"In addition, to better consolidate our conclusion that JOSD2 regulated LKB1 activity by removing K6-ub but not K63-ub, we also investigated the effects of JOSD2 on K63-ub of LKB1, as shown in supplementary Fig. S4f, g, neither overexpression nor depletion of JOSD2 posed effects on LKB1 K63-ub, suggested that as a DUB for LKB1, JOSD2 preferentially cleaved K6 linkage but not K63 linkage.Hence, these results indicated that JOSD2 was a bona fide DUB for LKB1, as JOSD2 bound to LKB1 and removed the K6-linked polyubiquitination on LKB1."
JOSD2 affects IMPDH2-K134R
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JOSD2 affects HY041004
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JOSD2 affects E3_Ub_ligase
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E3_Ub_ligase binds JOSD2. 1 / 1
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JOSD2 affects Carcinoma, Non-Small-Cell Lung
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JOSD2 activates Carcinoma, Non-Small-Cell Lung. 1 / 1
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JOSD2 affects Carcinoma, Hepatocellular
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JOSD2 activates Carcinoma, Hepatocellular. 1 / 1
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JOSD2 affects Body Weight
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JOSD2 activates Body Weight. 1 / 1
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JOSD2 affects BRCC3
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IMPDH2-K134R affects JOSD2
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IMPDH2 affects K63
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"Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-kappaB) and inflammation in macrophages."
HY04071 affects JOSD2
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ESCC affects JOSD2
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BRCC3 affects JOSD2
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AAV6 affects JOSD2
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