Differential Proteomic Analysis Reveals Protein Networks and Pathways that May Contribute to <i>Helicobacter pylori</i> FKBP‐Type PPIase‐Associated Gastric Diseases

Zhu, Yanmei; Gong, Yuehua; Li, Aodi; Chen, Moye; Kang, Dan; Li, Jun; Yuan, Yuan

doi:10.1002/prca.201700127

Cited by 5 publications

(3 citation statements)

References 40 publications

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“…IPA software v7.1 (Ingenuity Systems, Mountain View, CA) was used for network connection and pathway analysis (http://www.ingenuity.com). Proteins were categorized based on molecular function and published interactions with other proteins [59].…”

Section: Methodsmentioning

confidence: 99%

Novel Autoantibodies Related to Cell Death and DNA Repair Pathways in Systemic Lupus Erythematosus

Luo

Bao

Wang

et al. 2019

Genomics, Proteomics &Amp; Bioinformatics

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Systemic lupus erythematosus (SLE) is a complex autoimmune syndrome characterized by various co-existing autoantibodies (autoAbs) in patients’ blood. However, the full spectrum of autoAbs in SLE has not been comprehensively elucidated. In this study, a commercial platform bearing 9400 antigens (ProtoArray) was used to identify autoAbs that were significantly elevated in the sera of SLE patients. By comparing the autoAb profiles of SLE patients with those of healthy controls, we identified 437 IgG and 1213 IgM autoAbs that the expression levels were significantly increased in SLE (P < 0.05). Use of the ProtoArray platform uncovered over 300 novel autoAbs targeting a broad range of nuclear, cytoplasmic, and membrane antigens. Molecular interaction network analysis revealed that the antigens targeted by the autoAbs were most significantly enriched in cell death, cell cycle, and DNA repair pathways. A group of autoAbs associated with cell apoptosis and DNA repair function, including those targeting APEX1, AURKA, POLB, AGO1, HMGB1, IFIT5, MAPKAPK3, PADI4, RGS3, SRP19, UBE2S, and VRK1, were further validated by ELISA and Western blot in a larger cohort. In addition, the levels of autoAbs against APEX1, HMGB1, VRK1, AURKA, PADI4, and SRP19 were positively correlated with the level of anti-dsDNA in SLE patients. Comprehensive autoAb screening has identified novel autoAbs, which may shed light on potential pathogenic pathways leading to lupus.

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Section: Methodsmentioning

confidence: 99%

Novel Autoantibodies Related to Cell Death and DNA Repair Pathways in Systemic Lupus Erythematosus

Luo

Bao

Wang

et al. 2019

Genomics, Proteomics &Amp; Bioinformatics

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“…China) and quantified with bicinchoninic acid protein assay kit (Solarbio, Shanghai, P.R. China) 6. The same quantity of protein (30 µg per lane) was separated by 10% SDS-PAGE.…”

Section: Methodsmentioning

confidence: 99%

<p>C14orf159 suppresses gastric cancer cells’ invasion and proliferation by inactivating ERK signaling</p>

Zhu¹,

Li²,

Gao³

et al. 2019

CMAR

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Background C14orf159, a new protein, has been identified recently. But its expression in tissues and clinicopathologic correlation is still unknown. Patients and methods We carried out immunohistochemistry staining in 144 gastric cancer cases in this study. Then Western blot was used to detect the expression of protein. MTT and matrigel invasion assay were used to assess the biological effects. Results The immunohistochemical results indicated that the expression of C14orf159 in normal gastric mucosa close to cancer tissue was remarkably higher than that in stomach carcinoma samples (63.9% and 34.7%, respectively, P <0.001). Negative C14orf159 expression was dramatically related to high TNM stages ( P =0.033) and positive lymph node metastasis ( P =0.008). Once C14orf159 was overexpressed, the expression levels of phosphorylated ERK and its regulated downstream molecules, such as Snail, phosphorylated P90RSK and Cyclin D1, were decreased, while the expression level of E-cadherin was increased. Finally, the invasion and proliferation capacity of gastric cancer cells was inhibited. Conclusion In other words, loss of C14orf159 is associated with the progression of gastric cancer. The role of C14orf159 in repression of proliferation and invasion may be due to resuming E-cadherin and abolishing Snail and Cyclin D1 expression through inactivating ERK–P90RSK pathway.

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“…Cyclophilins are part of the immunophilin superfamily, with bacteria generally encoding two cyclophilin genes, ppiA and ppiB with one located in the cytoplasm and the other in the periplasm or outer membrane respectively (29). Cyclophilins catalyse the cis-trans isomerisation of xaa-proline bonds, a rate limiting step in protein folding, which is required for proteome homeostasis (30,31). Not only are cyclophilins required for optimal protein folding but in multiple bacterial systems cyclophilins are important for stress response and infectivity, suggesting a role in folding virulence factors.…”

Section: Introductionmentioning

confidence: 99%

Peptidyl-Prolyl Isomerase ppiB Is Essential for Proteome Homeostasis and Virulence in Burkholderia pseudomallei

et al. 2019

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Burkholderia pseudomallei is the causative agent of melioidosis, a disease endemic to Southeast Asia and northern Australia. Mortality rates in these areas are high even with antimicrobial treatment, and there are few options for effective therapy. Therefore, there is a need to identify antibacterial targets for the development of novel treatments. Cyclophilins are a family of highly conserved enzymes important in multiple cellular processes. Cyclophilins catalyze the cis-trans isomerization of xaa-proline bonds, a rate-limiting step in protein folding which has been shown to be important for bacterial virulence. B. pseudomallei carries a putative cyclophilin B gene, ppiB, the role of which was investigated. A B. pseudomallei ΔppiB (BpsΔppiB) mutant strain demonstrates impaired biofilm formation and reduced motility. Macrophage invasion and survival assays showed that although the BpsΔppiB strain retained the ability to infect macrophages, it had reduced survival and lacked the ability to spread cell to cell, indicating ppiB is essential for B. pseudomallei virulence. This is reflected in the BALB/c mouse infection model, demonstrating the requirement of ppiB for in vivo disease dissemination and progression. Proteomic analysis demonstrates that the loss of PpiB leads to pleiotropic effects, supporting the role of PpiB in maintaining proteome homeostasis. The loss of PpiB leads to decreased abundance of multiple virulence determinants, including flagellar machinery and alterations in type VI secretion system proteins. In addition, the loss of ppiB leads to increased sensitivity toward multiple antibiotics, including meropenem and doxycycline, highlighting ppiB inhibition as a promising antivirulence target to both treat B. pseudomallei infections and increase antibiotic efficacy.

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Differential Proteomic Analysis Reveals Protein Networks and Pathways that May Contribute to Helicobacter pylori FKBP‐Type PPIase‐Associated Gastric Diseases

Abstract: Our results provided insight on the protein interaction networks and signaling pathways that may contribute to PPIase-FKBP-associated gastric diseases and may lead to a better understanding of the mechanisms indicating the oncogenic effects of H. pylori PPIase-FKBP.

Cited by 5 publications

References 40 publications

Novel Autoantibodies Related to Cell Death and DNA Repair Pathways in Systemic Lupus Erythematosus

Novel Autoantibodies Related to Cell Death and DNA Repair Pathways in Systemic Lupus Erythematosus

<p>C14orf159 suppresses gastric cancer cells’ invasion and proliferation by inactivating ERK signaling</p>

Peptidyl-Prolyl Isomerase ppiB Is Essential for Proteome Homeostasis and Virulence in Burkholderia pseudomallei

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Differential Proteomic Analysis Reveals Protein Networks and Pathways that May Contribute to Helicobacter pylori FKBP‐Type PPIase‐Associated Gastric Diseases

Abstract: Our results provided insight on the protein interaction networks and signaling pathways that may contribute to PPIase-FKBP-associated gastric diseases and may lead to a better understanding of the mechanisms indicating the oncogenic effects of H. pylori PPIase-FKBP.

Cited by 5 publications

References 40 publications

Novel Autoantibodies Related to Cell Death and DNA Repair Pathways in Systemic Lupus Erythematosus

Novel Autoantibodies Related to Cell Death and DNA Repair Pathways in Systemic Lupus Erythematosus

<p>C14orf159 suppresses gastric cancer cells&rsquo; invasion and proliferation by inactivating ERK signaling</p>

Peptidyl-Prolyl Isomerase ppiB Is Essential for Proteome Homeostasis and Virulence in Burkholderia pseudomallei

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<p>C14orf159 suppresses gastric cancer cells’ invasion and proliferation by inactivating ERK signaling</p>