Transcriptional repression of IKKβ by p53 in arsenite-induced GADD45α accumulation and apoptosis

Hu, Yongliang; Jin, Rui; Gao, Ming; Xu, Huan; Zou, Shuxian; Li, Xiaoguang; Chen, Xing; Wang, Qiyu; Wang, Hongli; Feng, Jie; Hu, Meiru; Song, Lun

doi:10.1038/s41388-018-0478-7

Cited by 17 publications

(9 citation statements)

References 38 publications

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“…In addition, the stability of crucial factors in regulatory pathways may affect signal transduction. IKBKB could promote the stability of MDM2 ( 42 ), which can interact with MAPSK3 to promote STAT3 degradation ( 43 ). In conclusion, the proteins we screened have critical functions in cellular biological processes and lipid metabolism and may modulate the adipocytokine signaling pathway in a synergistic mode.…”

Section: Discussionmentioning

confidence: 99%

Deciphering Risperidone-Induced Lipogenesis by Network Pharmacology and Molecular Validation

Yang

Huang

et al. 2022

Front. Psychiatry

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BackgroundRisperidone is an atypical antipsychotic that can cause substantial weight gain. The pharmacological targets and molecular mechanisms related to risperidone-induced lipogenesis (RIL) remain to be elucidated. Therefore, network pharmacology and further experimental validation were undertaken to explore the action mechanisms of RIL.MethodsRILs were systematically analyzed by integrating multiple databases through integrated network pharmacology, transcriptomics, molecular docking, and molecular experiment analysis. The potential signaling pathways for RIL were identified and experimentally validated using gene ontology (GO) enrichment and Kyoto encyclopedia of genes and genomes (KEGG) analysis.ResultsRisperidone promotes adipocyte differentiation and lipid accumulation through Oil Red O staining and reverse transcription-polymerase chain reaction (RT-PCR). After network pharmacology and GO analysis, risperidone was found to influence cellular metabolism. In addition, risperidone influences adipocyte metabolism, differentiation, and lipid accumulation-related functions through transcriptome analysis. Intersecting analysis, molecular docking, and pathway validation analysis showed that risperidone influences the adipocytokine signaling pathway by targeting MAPK14 (mitogen-activated protein kinase 14), MAPK8 (mitogen-activated protein kinase 8), and RXRA (retinoic acid receptor RXR-alpha), thereby inhibiting long-chain fatty acid β-oxidation by decreasing STAT3 (signal transducer and activator of transcription 3) expression and phosphorylation.ConclusionRisperidone increases adipocyte lipid accumulation by plausibly inhibiting long-chain fatty acid β-oxidation through targeting MAPK14 and MAPK8.

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Section: Discussionmentioning

confidence: 99%

Deciphering Risperidone-Induced Lipogenesis by Network Pharmacology and Molecular Validation

Yang

Huang

et al. 2022

Front. Psychiatry

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“…Ubiquitination, an important event for protein relocation and degradation, is emerging as a new mechanism for immune regulation [ 28 ]. In the present study, in despite the fact that the loading of endotoxin-containing pathogen facilitate the formation of Akt+ IKKα/β+ Rab5+ signalosome, the exact mechanisms that the endosomal relocation of Akt and IKK promoting endotoxin-containing pathogen-derived cross-presentation are still to be clarified.…”

Section: Discussionmentioning

confidence: 99%

Akt+ IKKα/β+ Rab5+ Signalosome Mediate the Endosomal Recruitment of Sec61 and Contribute to Cross-Presentation in Bone Marrow Precursor Cells

You

et al. 2020

Vaccines

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Cross-presentation in dendritic cells (DC) requires the endosomal relocations of internalized antigens and the endoplasmic reticulum protein Sec61. Despite the fact that endotoxin-containing pathogen and endotoxin-free antigen have different effects on protein kinase B (Akt) and I-kappa B Kinase α/β (IKKα/β) activation, the exact roles of Akt phosphorylation, IKKα or IKKβ activation in endotoxin-containing pathogen-derived cross-presentation are poorly understood. In this study, endotoxin-free ovalbumin supplemented with endotoxin was used as a model pathogen. We investigated the effects of endotoxin-containing pathogen and endotoxin-free antigen on Akt phosphorylation, IKKα/β activation, and explored the mechanisms that the endotoxin-containing pathogen orchestrating the endosomal recruitment of Sec61 of the cross-presentation in bone marrow precursor cells (BMPC). We demonstrated that endotoxin-containing pathogen and endotoxin-free antigen efficiently induced the phosphorylation of Akt-IKKα/β and Akt-IKKα, respectively. Endotoxin-containing pathogen derived Akt+ IKKα/β+ Rab5+ signalosome, together with augmented the recruitment of Sec61 toward endosome, lead to the increased cross-presentation in BMPC. Importantly, the endosomal recruitment of Sec61 was partly mediated by the formation of Akt+ IKKα/β+ signalosome. Thus, these data suggest that Akt+ IKKα/β+ Rab5+ signalosome contribute to endotoxin-containing pathogen-induced the endosomal recruitment of Sec61 and the superior efficacy of cross-presentation in BMPC.

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“…The proteins encoding by PER2, GADD45A, and TPD52 genes are also involved in the cancer cell proliferation and tumor growth and are dysregulated in cancer cells (Wang et al 2016;Xiang et al 2018;Xiong et al 2018;Zhang et al 2018;Hu et al 2019;Rahman et al 2019). At the same time, the expression of these genes was resistant to the silencing of adipokine NAMPT in the glioma cells.…”

Section: Discussionmentioning

confidence: 99%

Silencing of NAMPT leads to up-regulation of insulin receptor substrate 1 gene expression in U87 glioma cells

Tsymbal

Minchenko

Luzina

et al. 2020

Endocrine Regulations

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Objective. The aim of the present study was to investigate the effect of adipokine NAMPT (nicotinamide phosphoribosyltransferase) silencing on the expression of genes encoding IRS1 (insulin receptor substrate 1) and some other proliferation related proteins in U87 glioma cells for evaluation of the possible significance of this adipokine in intergenic interactions.Methods. The silencing of NAMPT mRNA was introduced by NAMPT specific siRNA. The expression level of NAMPT, IGFBP3, IRS1, HK2, PER2, CLU, BNIP3, TPD52, GADD45A, and MKI67 genes was studied in U87 glioma cells by quantitative polymerase chain reaction. Anti-visfatin antibody was used for detection of NAMPT protein by Western-blot analysis.Results. It was shown that the silencing of NAMPT mRNA led to a strong down-regulation of NAMPT protein and significant modification of the expression of IRS1, IGFBP3, CLU, HK2, BNIP3, and MKI67 genes in glioma cells and a strong up-regulation of IGFBP3 and IRS1 and down-regulation of CLU, BNIP3, HK2, and MKI67 gene expressions. At the same time, no significant changes were detected in the expression of GADD45A, PER2, and TPD52 genes in glioma cells treated by siRNA specific to NAMPT. Furthermore, the silencing of NAMPT mRNA suppressed the glioma cell proliferation.Conclusions. Results of this investigation demonstrated that silencing of NAMPT mRNA with corresponding down-regulation of NAMPT protein and suppression of the glioma cell proliferation affected the expression of IRS1 gene as well as many other genes encoding the proliferation related proteins. It is possible that dysregulation of most of the studied genes in glioma cells after silencing of NAMPT is reflected by a complex of intergenic interactions and that NAMPT is an important factor for genome stability and regulatory mechanisms contributing to the control of glioma cell metabolism and proliferation.

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Transcriptional repression of IKKβ by p53 in arsenite-induced GADD45α accumulation and apoptosis

Cited by 17 publications

References 38 publications

Deciphering Risperidone-Induced Lipogenesis by Network Pharmacology and Molecular Validation

Deciphering Risperidone-Induced Lipogenesis by Network Pharmacology and Molecular Validation

Akt+ IKKα/β+ Rab5+ Signalosome Mediate the Endosomal Recruitment of Sec61 and Contribute to Cross-Presentation in Bone Marrow Precursor Cells

Silencing of NAMPT leads to up-regulation of insulin receptor substrate 1 gene expression in U87 glioma cells

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