Direct binding to integrins and loss of disulfide linkage in interleukin-1β (IL-1β) are involved in the agonistic action of IL-1β

Takada, Yoko; Yu, Jinqing; Fujita, Masaaki; Saegusa, Jun; Wu, Chun‐Yi; Takada, Yoshikazu

doi:10.1074/jbc.m117.818302

Cited by 18 publications

(15 citation statements)

References 28 publications

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“…ITGB1 was an important beta subset, because it could regulate cell migration and was regarded as a prometastatic gene for lung cancer [67]. ITGB1 also participated in signal transduction; for example, ITGB1 was an important part of IL1B receptor and essential for IL1B signaling [68]. Those findings clearly demonstrated that abnormal ubiquitination contributed to tumor invasion and distant metastasis.…”

Section: Abnormal Ubiquitination Is Closely Related To Tumor Invasionmentioning

confidence: 89%

Label-free quantitative identification of abnormally ubiquitinated proteins as useful biomarkers for human lung squamous cell carcinomas

Chen²,

Zhuang

et al. 2020

EPMA Journal

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Background Ubiquitination is an important molecular event in lung squamous cell carcinoma (LSCC), which currently is mainly studied in nonsmall cell lung carcinoma cell models but lacking of ubiquitination studies on LSCC tissues. Here, we presented the ubiquitinated protein profiles of LSCC tissues to explore ubiquitination-involved molecular network alterations and identify abnormally ubiquitinated proteins as useful biomarkers for predictive, preventive, and personalized medicine (PPPM) in LSCC. Methods Anti-ubiquitin antibody-based enrichment coupled with LC-MS/MS was used to identify differentially ubiquitinated proteins (DUPs) between LSCC and control tissues, followed by integrative omics analyses to identify abnormally ubiquitinated protein biomarkers for LSCC. Results Totally, 400 DUPs with 654 ubiquitination sites were identified,, and motifs AX (1/2/3)-K* were prone to be ubiquitinated in LSCC tissues. Those DUPs were involved in multiple molecular network systems, including the ubiquitinproteasome system (UPS), cell metabolism, cell adhesion, and signal transduction. Totally, 44 hub molecules were revealed by protein-protein interaction network analysis, followed by survival analysis in TCGA database (494 LSCC patients and 20,530 genes) to obtain 18 prognosis-related mRNAs, of which the highly expressed mRNAs VIM and IGF1R were correlated with poorer prognosis, while the highly expressed mRNA ABCC1 was correlated with better prognosis. VIM-encoded protein vimentin and ABCC1-encoded protein MRP1 were increased in LSCC, which were all associated with poor prognosis. Proteasome-inhibited experiments demonstrated that vimentin and MRP1 were degraded through UPS. Quantitative ubiquitinomics found ubiquitination level was decreased in vimentin and increased in MRP1 in LSCC. These findings showed that the increased vimentin in LSCC might be derived from its decreased ubiquitination level and that the increased MRP1 in LSCC might be derived from its protein synthesis > degradation. GSEA and co-expression gene analyses revealed that VIM and Electronic supplementary material The online version of this article (

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Section: Abnormal Ubiquitination Is Closely Related To Tumor Invasionmentioning

confidence: 89%

Label-free quantitative identification of abnormally ubiquitinated proteins as useful biomarkers for human lung squamous cell carcinomas

Chen²,

Zhuang

et al. 2020

EPMA Journal

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“…We have reported that several cytokines (FGF1, IGF1, neuregulin-1, and fractalkine) directly bind to integrins, and these interactions lead to ternary complex formation (integringrowth factor-cognate receptor), which is required for their signaling functions (21,24,(35)(36)(37)(38)(39). Recently, we found that direct binding of integrins to IL-1b plays a critical role in IL-1b signaling (40). This suggests that cross-talk between integrins and growth factor/cytokine receptors through direct integrin binding is a universal mechanism in growth factor/cytokine-mediated signaling.…”

Section: Discussionmentioning

confidence: 99%

Integrin Binding to the Trimeric Interface of CD40L Plays a Critical Role in CD40/CD40L Signaling

Takada

Shimoda

et al. 2019

The Journal of Immunology

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CD40L plays a major role in immune response and is a major therapeutic target for inflammation. Integrin a5b1 and CD40 simultaneously bind to CD40L. It is unclear if a5b1 and CD40 work together in CD40/CD40L signaling or how a5b1 binds to CD40L. In this article, we describe that the integrin-binding site of human CD40L is predicted to be located in the trimeric interface by docking simulation. Mutations in the predicted integrin-binding site markedly reduced the binding of a5b1 to CD40L. Several CD40L mutants defective in integrin binding were defective in NF-kB activation and B cell activation and suppressed CD40L signaling induced by wild-type CD40L; however, they still bound to CD40. These findings suggest that integrin a5b1 binds to monomeric CD40L through the binding site in the trimeric interface of CD40L, and this plays a critical role in CD40/CD40L signaling. Integrin avb3, a widely distributed vascular integrin, bound to CD40L in a KGD-independent manner, suggesting that avb3 is a new CD40L receptor. Several missense mutations in CD40L that induce immunodeficiency with hyper-IgM syndrome type 1 (HIGM1) are clustered in the integrin-binding site of the trimeric interface. These HIGM1 CD40L mutants were defective in binding to a5b1 and avb3 (but not to CD40), suggesting that the defect in integrin binding may be a causal factor of HIGM1. These findings suggest that a5b1 and avb3 bind to the overlapping binding site in the trimeric interface of monomeric CD40L and generate integrin-CD40L-CD40 ternary complex. CD40L mutants defective in integrins have potential as antagonists of CD40/CD40L signaling.

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“…Studying the signaling pathway of gene involvement could help us to understand the role of gene in AD and further understand the pathological process or cause of AD. ITGB1 was a receptor for IL1 β and binding was essential for IL1 β signaling [ 15 ]. RAB7A was a key regulator in endolysosomal trafficking [ 16 ], playing important roles in neurotrophin transport, lipid metabolism, microbial pathogen infection, and survival [ 17 , 18 ].…”

Section: Resultsmentioning

confidence: 99%

Differential Expression of mRNAs in the Brain Tissues of Patients with Alzheimer’s Disease Based on GEO Expression Profile and Its Clinical Significance

Liu

et al. 2019

BioMed Research International

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Background. Early diagnosis of Alzheimer’s disease (AD) is an urgent point for AD prevention and treatment. The biomarkers of AD still remain indefinite. Based on the bioinformatics analysis of mRNA differential expressions in the brain tissues and the peripheral blood samples of Alzheimer’s disease (AD) patients, we investigated the target mRNAs that could be used as an AD biomarker and developed a new effective, practical clinical examination program. Methods. We compared the AD peripheral blood mononuclear cells (PBMCs) expression dataset (GEO accession GSE4226 and GSE18309) with AD brain tissue expression datasets (GEO accessions GSE1297 and GSE5281) from GEO in the present study. The GEO gene database was used to download the appropriate gene expression profiles to analyze the differential mRNA expressions between brain tissue and blood of AD patients and normal elderly. The Venn diagram was used to screen out the differential expression of mRNAs between the brain tissue and blood. The protein-protein interaction network map (PPI) was used to view the correlation between the possible genes. GO (gene ontology) and KEGG (Kyoto Gene and Genomic Encyclopedia) were used for gene enrichment analysis to determine the major affected genes and the function or pathway. Results. Bioinformatics analysis revealed that there were differentially expressed genes in peripheral blood and hippocampus of AD patients. There were 4958 differential mRNAs in GSE18309, 577 differential mRNAs in GSE4226 in AD PBMCs sample, 7464 differential mRNAs in GSE5281, and 317 differential mRNAs in GSE129 in AD brain tissues, when comparing between AD patients and healthy elderly. Two mRNAs of RAB7A and ITGB1 coexpressed in hippocampus and peripheral blood were screened. Furthermore, functions of differential genes were enriched by the PPI network map, GO, and KEGG analysis, and finally the chemotaxis, adhesion, and inflammatory reactions were found out, respectively. Conclusions. ITGB1 and RAB7A mRNA expressions were both changed in hippocampus and PBMCs, highly suggested being used as an AD biomarker with AD. Also, according to the results of this analysis, it is indicated that we can test the blood routine of the elderly for 2-3 years at a frequency of 6 months or one year. When a patient continuously detects the inflammatory manifestations, it is indicated as a potentially high-risk AD patient for AD prevention.

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Direct binding to integrins and loss of disulfide linkage in interleukin-1β (IL-1β) are involved in the agonistic action of IL-1β

Cited by 18 publications

References 28 publications

Label-free quantitative identification of abnormally ubiquitinated proteins as useful biomarkers for human lung squamous cell carcinomas

Label-free quantitative identification of abnormally ubiquitinated proteins as useful biomarkers for human lung squamous cell carcinomas

Integrin Binding to the Trimeric Interface of CD40L Plays a Critical Role in CD40/CD40L Signaling

Differential Expression of mRNAs in the Brain Tissues of Patients with Alzheimer’s Disease Based on GEO Expression Profile and Its Clinical Significance

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