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Search results for: interacting


#32770827   2020/08/08 To Up

MAPRE1 promotes cell cycle progression of hepatocellular carcinoma cells by interacting with CDK2.

Targeting cyclin-dependent kinases (CDKs) is a promising method of therapy cancer. Unfortunately, the efficacy of CDK inhibitors in hepatocellular carcinoma (HCC) is limited, due in part to incomplete understanding of cell cycle progression and a lack of specific biomarkers to adequately identify which patients may be responsive to CDK inhibitors. In the present study, we report that MAPRE1, a gene involved in cell cycle and microtubule regulation, is significantly increased in HCC tissue, promotes HCC cell proliferation, enhances in vitro tumorigenesis, and associates with poor prognosis of HCC. We demonstrate that MAPRE1 binds with CDK2, resulting in the hyper- phosphorylation of the CDK2 Thr161 residue in HCC cells. Our findings reveal that targeting MAPRE1 might be an effective therapeutic strategy in HCC, and suggest that MAPRE1 expression might provide a promising biomarker to stratify patients with HCC who may benefit from treatment with CDK inhibitors. This article is protected by copyright. All rights reserved.
Xing-Hua Liang, Zheng-Ping Feng, Fo-Qiu Liu, Rong Yan, Liang-Yu Yin, Hao Shen, Hai-Lin Lu

1307 related Products with: MAPRE1 promotes cell cycle progression of hepatocellular carcinoma cells by interacting with CDK2.

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#32770173   2020/08/07 To Up

Sirtuin 3 deficiency exacerbates diabetic cardiomyopathy via necroptosis enhancement and NLRP3 activation.

Sirtuin 3 (SIRT3) is a potential therapeutic target for cardiovascular, metabolic, and other aging-related diseases. In this study, we investigated the role of SIRT3 in diabetic cardiomyopathy (DCM). Mice were injected with streptozotocin (STZ, 60 mg/kg, ip) to induce diabetes mellitus. Our proteomics analysis revealed that SIRT3 expression in the myocardium of diabetic mice was lower than that of control mice, as subsequently confirmed by real-time PCR and Western blotting. To explore the role of SIRT3 in DCM, SIRT3-knockout mice and 129S1/SvImJ wild-type mice were injected with STZ. We found that diabetic mice with SIRT3 deficiency exhibited aggravated cardiac dysfunction, increased lactate dehydrogenase (LDH) level in the serum, decreased adenosine triphosphate (ATP) level in the myocardium, exacerbated myocardial injury, and promoted myocardial reactive oxygen species (ROS) accumulation. Neonatal rat cardiomyocytes were transfected with SIRT3 siRNA, then exposed to high glucose (HG, 25.5 mM). We found that downregulation of SIRT3 further increased LDH release, decreased ATP level, suppressed the mitochondrial membrane potential, and elevated oxidative stress in HG-treated cardiomyocytes. SIRT3 deficiency further raised expression of necroptosis-related proteins including receptor-interacting protein kinase 1 (RIPK1), RIPK3, and cleaved caspase 3, and upregulated the expression of inflammation-related proteins including NLR family pyrin domain-containing protein 3 (NLRP3), caspase 1 p20, and interleukin-1β both in vitro and in vivo. Collectively, SIRT3 deficiency aggravated hyperglycemia-induced mitochondrial damage, increased ROS accumulation, promoted necroptosis, possibly activated the NLRP3 inflammasome, and ultimately exacerbated DCM in the mice. These results suggest that SIRT3 can be a molecular intervention target for the prevention and treatment of DCM.
Shu Song, Yue Ding, Guo-Liang Dai, Yue Zhang, Meng-Ting Xu, Jie-Ru Shen, Ting-Ting Chen, Yun Chen, Guo-Liang Meng

2036 related Products with: Sirtuin 3 deficiency exacerbates diabetic cardiomyopathy via necroptosis enhancement and NLRP3 activation.

30µg/vial5mg5 x 2 ml25 x 2 ml10 mg25 mg0.25 mg25 mg 25 G5 g100ug/vial

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#32770038   2020/08/07 To Up

A neural circuit model for human sensorimotor timing.

Humans and animals can effortlessly coordinate their movements with external stimuli. This capacity indicates that sensory inputs can rapidly and flexibly reconfigure the ongoing dynamics in the neural circuits that control movements. Here, we develop a circuit-level model that coordinates movement times with expected and unexpected temporal events. The model consists of two interacting modules, a motor planning module that controls movement times and a sensory anticipation module that anticipates external events. Both modules harbor a reservoir of latent dynamics, and their interaction forms a control system whose output is adjusted adaptively to minimize timing errors. We show that the model's output matches human behavior in a range of tasks including time interval production, periodic production, synchronization/continuation, and Bayesian time interval reproduction. These results demonstrate how recurrent interactions in a simple and modular neural circuit could create the dynamics needed to control timing behavior.
Seth W Egger, Nhat M Le, Mehrdad Jazayeri

2164 related Products with: A neural circuit model for human sensorimotor timing.

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#32770028   2020/08/07 To Up

Mutant p53 induces Golgi tubulo-vesiculation driving a prometastatic secretome.

TP53 missense mutations leading to the expression of mutant p53 oncoproteins are frequent driver events during tumorigenesis. p53 mutants promote tumor growth, metastasis and chemoresistance by affecting fundamental cellular pathways and functions. Here, we demonstrate that p53 mutants modify structure and function of the Golgi apparatus, culminating in the increased release of a pro-malignant secretome by tumor cells and primary fibroblasts from patients with Li-Fraumeni cancer predisposition syndrome. Mechanistically, interacting with the hypoxia responsive factor HIF1α, mutant p53 induces the expression of miR-30d, which in turn causes tubulo-vesiculation of the Golgi apparatus, leading to enhanced vesicular trafficking and secretion. The mut-p53/HIF1α/miR-30d axis potentiates the release of soluble factors and the deposition and remodeling of the ECM, affecting mechano-signaling and stromal cells activation within the tumor microenvironment, thereby enhancing tumor growth and metastatic colonization.
Valeria Capaci, Lorenzo Bascetta, Marco Fantuz, Galina V Beznoussenko, Roberta Sommaggio, Valeria Cancila, Andrea Bisso, Elena Campaner, Alexander A Mironov, Jacek R Wiśniewski, Luisa Ulloa Severino, Denis Scaini, Fleur Bossi, Jodi Lees, Noa Alon, Ledia Brunga, David Malkin, Silvano Piazza, Licio Collavin, Antonio Rosato, Silvio Bicciato, Claudio Tripodo, Fiamma Mantovani, Giannino Del Sal

1043 related Products with: Mutant p53 induces Golgi tubulo-vesiculation driving a prometastatic secretome.

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#32769939   // To Up

Screening of significant biomarkers with poor prognosis in hepatocellular carcinoma via bioinformatics analysis.

Hepatocellular carcinoma (HCC) is a malignant tumor with unsatisfactory prognosis. The abnormal genes expression is significantly associated with initiation and poor prognosis of HCC. The aim of the present study was to identify molecular biomarkers related to the initiation and development of HCC via bioinformatics analysis, so as to provide a certain molecular mechanism for individualized treatment of hepatocellular carcinoma.Three datasets (GSE101685, GSE112790, and GSE121248) from the GEO database were used for the bioinformatics analysis. Differentially expressed genes (DEGs) of HCC and normal liver samples were obtained using GEO2R online tools. Gene ontology term and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis were conducted via the Database for Annotation, Visualization, and Integrated Discovery online bioinformatics tool. The protein-protein interaction (PPI) network was constructed by the Search Tool for the Retrieval of Interacting Genes database and hub genes were visualized by Cytoscape. Survival analysis and RNA sequencing expression were conducted by UALCAN and Gene Expression Profiling Interactive Analysis.A total of 115 shared DEGs were identified, including 30 upregulated genes and 85 downregulated genes in HCC samples. P53 signaling pathway and cell cycle were the major enriched pathways for the upregulated DEGs whereas metabolism-related pathways were the major enriched pathways for the downregulated DEGs. The PPI network was established with 105 nodes and 249 edges and 3 significant modules were identified via molecular complex detection. Additionally, 17 candidate genes from these 3 modules were significantly correlated with HCC patient survival and 15 of 17 genes exhibited high expression level in HCC samples. Moreover, 4 hub genes (CCNB1, CDK1, RRM2, BUB1B) were identified for further reanalysis of KEGG pathway, and enriched in 2 pathways, the P53 signaling pathway and cell cycle pathway.Overexpression of CCNB1, CDK1, RRM2, and BUB1B in HCC samples was correlated with poor survival in HCC patients, which could be potential therapeutic targets for HCC.
Quanquan Sun, Peng Liu, Bin Long, Yuan Zhu, Tongxin Liu

2856 related Products with: Screening of significant biomarkers with poor prognosis in hepatocellular carcinoma via bioinformatics analysis.

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#32768969   2020/07/06 To Up

Proteomic analysis of extracellular vesicles released from heat-stroked hepatocytes reveals promotion of programmed cell death pathway.

Liver injury is a common complication of severe heat stroke (HS). Extracellular vesicles (EVs) are part of a novel pathway mediating intercellular communication. Whether EVs are involved in the pathogenesis underlying HS-induced liver injury remains unknown. Here, we explored the role of hepatocyte EVs in HS-induced liver injury and their protein regulation patterns after HS induction. Isobaric tags for relative and absolute quantification technology (iTRAQ) and liquid chromatography-tandem mass spectrometry analysis identified changes in the proteomic profiles of hepatocyte-derived heat-stroked EVs, and we identified 53 up-regulated proteins. Bioinformatics analysis verified that the regulation of programmed cell death was the most significant altered pathway. To clarify the effect of HS hepatocyte-derived EVs in inducing hepatocyte-programmed death and injury, they were added to recipient hepatocytes and injected into mice. This treatment significantly induced the synthesis of apoptosis (caspase-3/8) and necroptosis-associated proteins [receptor-interacting protein 1 (RIP1), RIP3, and mixed lineage kinase domain-like protein]; moreover, it increased the numbers of apoptotic and necroptotic cells in hepatocytes and liver tissues and increased the levels of biochemical liver injury markers (alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase). Our study is the first comprehensive analysis of the hepatocyte-derived heat-stroked EV proteome confirming the induction of liver injury by Evs. We provide a novel explanation for the pathological mechanism underlying HS-induced liver injury.
Yue Li, Xintao Zhu, Guozhen Wang, Huasheng Tong, Lei Su, Xu Li

1023 related Products with: Proteomic analysis of extracellular vesicles released from heat-stroked hepatocytes reveals promotion of programmed cell death pathway.

100ug Lyophilized100ug Lyophilized100ug Lyophilized1.5 x 10^6 cells1.5x10(6) cells100ug Lyophilized2 Pieces/Box100ug Lyophilized100ug Lyophilized100ug Lyophilized1.5 x 10^6 cells100ug Lyophilized

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#32768948   2020/07/09 To Up

MTMR14 protects against hepatic ischemia-reperfusion injury through interacting with AKT signaling in vivo and in vitro.

Hepatic ischemia-reperfusion (IR) injury is characterized by severe inflammation and cell death. However, very few effective therapies are presently available for hepatic IR injury treatment. Here, we reported a protective function and the underlying mechanism of myotubularin-related protein 14 (MTMR14) during hepatic IR injury. Hepatocyte-specific MTMR14 knockout (HKO) and transgenic (TG) mice were subjected to hepatic IR operation to explore MTMR14 function in vivo. Primary hepatocytes isolated from MTMR14-HKO and MTMR14-TG mice were subjected to hypoxia/reoxygenation (HR) insult in vitro. We found that MTMR14 expression in liver tissues from individuals with hepatic IR was markedly decreased, and similar results were detected in mice with hepatic IR surgery. MTMR14-TG mice following hepatic IR operation had obviously ameliorated liver pathological changes, along with improved hepatic dysfunction, which was proved by the decreased serum alanine amino transferase (ALT) and aspartate amino transferase (AST) levels. MTMR14-HKO and MTMR14-TG animal models indicated that MTMR14 alleviated cell death and inflammatory response. In addition, MTMR14 inhibited nuclear transcription factor κB (NF-κB) signaling. Of note, promoting MTMR14 expression improved phosphatidylinositol 3-kinase/protein kinase-B (PI3K/AKT) pathway through a physical interaction with AKT, subsequently reducing cell death and inflammation. Therefore, MTMR14 is a protective factor during hepatic IR injury, and the MTMR14/AKT signaling is involved the pathogenesis hepatic IR injury. Improvement of this axis might be a novel therapeutic strategy for the prevention of this pathological process.
Shufang Li, Meng Zhang, Bei Zhang

2204 related Products with: MTMR14 protects against hepatic ischemia-reperfusion injury through interacting with AKT signaling in vivo and in vitro.

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#32768240   2020/06/04 To Up

Target genes directly regulated by Eha are required for Edwardsiella tarda survival within macrophages.

Eha is a virulence regulator in Edwardsiella tarda (E. tarda). The present study examined how Eha regulated its target genes to affect the bacterial survival within the cells. We constructed the reporter a pGEX-4T-ehaflag plasmid expressing Eha tagged at its C terminus with the flag epitope, and introduced the plasmid into an eha mutant ET13 strain, and obtained a Cehaflag strain. The expression and activity of an EhaFlag fusion protein restored the survival of the Cehaflag as the wild type in macrophages by Western blotting and intracellular survival experiments. We used a monoclonal anti-Flag antibody to precipitate EhaFlag-DNA complexes using chromatic immunoprecipitation (ChIP). We then designed primers based on the differentially-expressed genes identified from RNA-sequencing, and identified ten Eha-interacting genes by qPCR. We amplified the promoter regions of the ten genes and the eha gene from ET13 strain by PCR, constructed pBD-PlacZ and pBD-PlacZ plasmids. The eha gene directly and positively regulated these target genes, and be negatively auto-regulated by Eha in E. tarda, as determined by comparing their β-Galactosidase activities. These target genes were distributed in the categories involved in the bacterial growth, movement and resistance to HO or acid. We further constructed a ETATCC_RS15225 mutant (△dcuA1), a ETATCC_ RS14855 mutant (△flgK) anda ETATCC_RS07650 mutant (ΔtnaA), and a partial complementary strains of △eha-tnaA and △eha-flgK and the complementary strains of CΔflgK and CΔtnaA. The ETATCC_RS15225 gene probably encoded a transporter protein DcuA1 at outer membrane with SDS-PAGE and RT-PCR. The ETATCC _RS14855 gene probably encoded FlgK protein and affected the bacterial motility. The ETATCC_RS07650 gene encoded Tryptophanase, which affected the bacterial survival within macrophages. With the assistance of these above strains, our results showed that the eha gene was able to regulate the ETATCC_RS15225 gene to express its outer membrane protein DcuA1, the ETATCC _RS14855 gene to control the flagellar motility and the ETATCC_RS07650 to affect the bacterial survival within macrophages. With the combination of other functions of above three genes, our results suggested that Eha directly regulates the target genes to affect E. tarda to survive within the cells.
Daqing Gao, Nian Liu, Chang Tian, Rui Liu, Lijiang Zhao, Yuanyuan Zhang, Enjin Zheng, Chengping Lu

1365 related Products with: Target genes directly regulated by Eha are required for Edwardsiella tarda survival within macrophages.

25 µg0.2 mg100 ml100 TESTS0.2 mg0.1 mg0.1 ml25 µg0.1 mg250 ml0.25 mg1 ml

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#32768236   2020/07/13 To Up

Cellular poly(C) binding protein 2 interacts with porcine epidemic diarrhea virus papain-like protease 1 and supports viral replication.

Porcine epidemic diarrhea virus (PEDV) belongs to the Alphacoronavirus genus in the Coronaviridae family. Similar to other coronaviruses, PEDV encodes two papain-like proteases. Papain-like protease (PLP)2 has been proposed to play a key role in antagonizing host innate immunity. However, the function of PLP1 remains unclear. In this study, we found that overexpression of PLP1 significantly promoted PEDV replication and inhibited production of interferon-β. Immunoprecipitation and mass spectrometry were used to identify cellular interaction partners of PLP1. Host cell poly(C) binding protein 2 (PCBP2) was determined to bind and interact with PLP1. Both endogenous and overexpressed PCBP2 co-localized with PLP1 in the cytoplasm. Overexpression of PLP1 upregulated expression of PCBP2. Furthermore, overexpression of PCBP2 promoted PEDV replication. Silencing of endogenous PCBP2 using small interfering RNAs attenuated PEDV replication. Taken together, these data demonstrated that PLP1 negatively regulated the production of type 1 interferon by interacting with PCBP2 and promoted PEDV replication.
Pengfei Zhang, Linyang Yu, Jianguo Dong, Yanling Liu, Leyi Zhang, Pengshuai Liang, Lei Wang, Bin Chen, Li Huang, Changxu Song

1499 related Products with: Cellular poly(C) binding protein 2 interacts with porcine epidemic diarrhea virus papain-like protease 1 and supports viral replication.

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#32767654   2020/08/07 To Up

LDL receptor-related protein LRP6 senses nutrient levels and regulates Hippo signaling.

Controlled cell growth and proliferation are essential for tissue homeostasis and development. Wnt and Hippo signaling are well known as positive and negative regulators of cell proliferation, respectively. The regulation of Hippo signaling by the Wnt pathway has been shown, but how and which components of Wnt signaling are involved in the activation of Hippo signaling during nutrient starvation are unknown. Here, we report that a reduction in the level of low-density lipoprotein receptor-related protein 6 (LRP6) during nutrient starvation induces phosphorylation and cytoplasmic localization of YAP, inhibiting YAP-dependent transcription. Phosphorylation of YAP via loss of LRP6 is mediated by large tumor suppressor kinases 1/2 (LATS1/2) and Merlin. We found that O-GlcNAcylation of LRP6 was reduced, and the overall amount of LRP6 was decreased via endocytosis-mediated lysosomal degradation during nutrient starvation. Merlin binds to LRP6; when LRP6 is less O-GlcNAcylated, Merlin dissociates from it and becomes capable of interacting with LATS1 to induce phosphorylation of YAP. Our data suggest that LRP6 has unexpected roles as a nutrient sensor and Hippo signaling regulator.
Wonyoung Jeong, Soyoung Kim, Ukjin Lee, Zhendong A Zhong, Mikhail Savitsky, Hyeryun Kwon, Jiyoung Kim, Taebok Lee, Jin Won Cho, Bart O Williams, Vladimir L Katanaev, Eek-Hoon Jho

1536 related Products with: LDL receptor-related protein LRP6 senses nutrient levels and regulates Hippo signaling.

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