Inhibition of TRAF6 ubiquitin-ligase activity by PRDX1 leads to inhibition of NFKB activation and autophagy activation

Min, Young Ki; Kim, Mi-Jeong; Lee, Sena; Chun, Eunyoung; Lee, Ki-Young

doi:10.1080/15548627.2018.1474995

Cited by 148 publications

(158 citation statements)

References 47 publications

(98 reference statements)

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“…Moreover, we found that p-IκBα and p-p65 were highly expressed and that IκBα was detected at low levels in BV2 cells after LPS treatment: Ala inhibited the degradation of IκBα but had no significant effect on p65. The p65 subunit of the activated NF-κB translocated from the cytoplasm to the nucleus, where it induced the expression of downstream target genes, including COX-2, iNOS, IL-1β, and IL-6 [44,45]. Increasingly, more research has demonstrated that the NF-κB p65 subunit is primarily retained in the cytoplasm of unstimulated BV2 cells but translocates to the nucleus when these cells are stimulated with LPS [32,46].…”

Section: Discussionmentioning

confidence: 99%

Anti-Neuroinflammatory Effect of Alantolactone through the Suppression of the NF-κB and MAPK Signaling Pathways

Tan

Wang

et al. 2019

Cells

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Neuroinflammation is a major cause of central nervous system (CNS) damage and can result in long-term disability and mortality. Therefore, the development of effective anti-neuroinflammatory agents for neuroprotection is vital. To our surprise, the naturally occurring molecule alantolactone (Ala) was reported to significantly inhibit tumor growth and metastasis as a result of its excellent anti-inflammatory effects. Thus, we proposed that it could also act as an anti-neuroinflammatory agent. Thus, in this study, a coculture system of BV2 cells and PC12 cells were used as an in vitro neuroinflammatory model to investigate the anti-neuroinflammatory mechanism of Ala. The results indicated that Ala downregulated the expression of proinflammatory factors by suppressing the nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Further evaluation using a middle cerebral artery occlusion and reperfusion (MCAO/R) rat model supported the conclusion that Ala could (1) alleviate cerebral ischemia-reperfusion injury; (2) reduce neurological deficits, cerebral infarct volume, and brain edema; and (3) attenuate the apoptosis and necrosis of neurons. In sum, Ala demonstrates anti-neuroinflammatory properties that contribute to the amelioration of CNS damage, and it could be a promising candidate for future applications in CNS injury treatment.

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Section: Discussionmentioning

confidence: 99%

Anti-Neuroinflammatory Effect of Alantolactone through the Suppression of the NF-κB and MAPK Signaling Pathways

Tan

Wang

et al. 2019

Cells

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“…Moreover, it can enhance bactericidal activity and inhibit the invasion and migration of tumor cells. 17 Among the proteins identified by proteomics for ESCC, PRDX1 is considered a tumor-associated antigen for EC cells. In the present study, PRDX1 was shown to be a tumor suppressor gene that is highly expressed in three ESCC cell lines.…”

Section: Discussionmentioning

confidence: 99%

<p>Silencing of Peroxiredoxin 1 Inhibits the Proliferation of Esophageal Cancer Cells and Promotes Apoptosis by Inhibiting the Activity of the PI3K/AKT Pathway</p>

Song¹,

Liu²,

Cui³

et al. 2019

CMAR

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Objective: To study the effect of peroxiredoxin 1 (PRDX1) on esophageal squamous carcinoma cells and determine whether it plays a role in regulating the PI3K/AKT signaling pathway. Methods: Three esophageal squamous cell carcinoma cell lines (Eca-109, EC9706, and KYSE150) and one normal cell line (human esophageal epithelial cells) were selected. The protein expression of peroxiredoxin 1 (PRDX1) and the activity of the PI3K/AKT pathway were detected via Western blotting. The proliferation ability of cells was detected through the MTT assay and cell clone formation. Apoptosis was detected using flow cytometry. Subsequently, cells were treated with a PI3K/AKT pathway inhibitor and activator, alone or in combination with silencing of PRDX1, and the above indicators were re-tested. Results: The expression of PRDX1 and activity of PI3K/AKT pathway-associated proteins were higher in esophageal cancer cells than in normal esophageal epithelial cells. Compared with normal human esophageal epithelial cells, the proliferation of the three types of esophageal cancer cells was increased, whereas their level of apoptosis was decreased (p<0.05). In Eca-109 cells (cell line with silenced expression of PRDX1), the expression of PRDX1 was significantly decreased. In contrast to the control group, the proliferation and clonality of cells in the silencing PRDX1 group was decreased, the proportion of apoptotic cells was increased, and the phosphorylation levels of PI3K and AKT were decreased (p<0.05). Compared with the control group, treatment with the inhibitor LY294002 alone significantly inhibited cell proliferation and promoted apoptosis (p<0.05); this effect was similar to that observed in the silencing PRDX1 group. Conclusion: PRDX1 was highly expressed in esophageal cancer cells. Silencing of PRDX1 can inhibit the proliferation of esophageal cancer cells and promote apoptosis. The mechanism involved in this process may be related to the inhibition of the PI3K/AKT signaling pathway.

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“…The regulation of ubiquitination of EZH2 is complex, and several E3 ligases, such as Smurf2, β-TrCP, Praja1 and FOXP3, have been reported to be involved in these processes [37][38][39][40]. TRAF6 is a kind of adaptor protein and E3 ubiquitin ligase that belongs to the family of tumor necrosis factor receptorassociated factors (TRAFs), and plays a vital role in various solid tumors through activating multiple signaling pathways [41,42]. Recent study showed that TRAF6 could catalyze K63-linked polyubiquitination of EZH2 and promote its proteasome-dependent degradation in prostate cancer [26].…”

Section: Discussionmentioning

confidence: 99%

TRIM25 Regulates Oxaliplatin Resistance in Colorectal Cancer by Promoting EZH2 Stability

Zhou

Peng

Xiao

et al. 2020

Preprint

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Background Resistance to chemotherapy remains the major cause of treatment failure in patients with colorectal cancer (CRC). TRIM25, an E3-ubiquitin ligase, has been reported to play a vital role in tumorigenesis. This project aims to explore the function and mechanism of TRIM25 in regulating oxaliplatin resistance in colorectal cancer.Methods The expression of TRIM25 in colorectal cancer tissues were examined by publicly available dataset, Immunohistochemistry and western blot. Further survival analysis was conducted using Kaplan-Meier method. CCK8 assay, colony-formation assay, Annexin V-FITC /PI staining and xenograft tumor models were used for evaluating sensitivity of CRC cells to oxaliplatin. Sphere-formation assay, RT-PCR and limiting dilution assay were used to evaluate the influence of TRIM25 on stem cell properties of CRC cells. Co-immunoprecipitation, polyubiquitination assay and western bolt elucidate the mechanism by which TRIM25 regulates EZH2.Results Patients with high expression of TRIM25 have significantly higher recurrence rate (28.9% vs. 15.0%, P = 0.012) and worse disease-free survival (P = 0.006) than those with low TRIM25 expression. Downregulation of TRIM25 dramatically inhibited while TRIM25 overexpression enhanced CRC cells survival after oxaliplatin treatment. In addition, TRIM25 promotes stem cell properties of CRC cells both in vitro and in vivo (8 mice per group). Importantly, we demonstrated that TRIM25 inhibits the binding of E3-ubiquitin ligase TRAF6 to EZH2, thus stabilizing and upregulating EZH2 and promoting oxaliplatin resistance. Conclusions Our study provides evidence that TRIM25 is a novel epigenetic regulator of oxaliplatin resistance. Targeting TRIM25 might be a promising strategy for CRC treatment.

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Inhibition of TRAF6 ubiquitin-ligase activity by PRDX1 leads to inhibition of NFKB activation and autophagy activation

Cited by 148 publications

References 47 publications

Anti-Neuroinflammatory Effect of Alantolactone through the Suppression of the NF-κB and MAPK Signaling Pathways

Anti-Neuroinflammatory Effect of Alantolactone through the Suppression of the NF-κB and MAPK Signaling Pathways

<p>Silencing of Peroxiredoxin 1 Inhibits the Proliferation of Esophageal Cancer Cells and Promotes Apoptosis by Inhibiting the Activity of the PI3K/AKT Pathway</p>

TRIM25 Regulates Oxaliplatin Resistance in Colorectal Cancer by Promoting EZH2 Stability

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