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http://krishi.icar.gov.in/jspui/handle/123456789/72347
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DC Field | Value | Language |
---|---|---|
dc.contributor.author | Mobashar Hussain Urf Turabe Fazil | en_US |
dc.contributor.author | Chandra Sekhar Chirumamilla | en_US |
dc.contributor.author | Claudina Perez-Novo | en_US |
dc.contributor.author | Brandon Han Siang Wong | en_US |
dc.contributor.author | Sunil Kumar | en_US |
dc.contributor.author | Siu Kwan Sze | en_US |
dc.contributor.author | Wim Vanden Berghe | en_US |
dc.contributor.author | Navin Kumar Verma | en_US |
dc.date.accessioned | 2022-05-21T05:12:48Z | - |
dc.date.available | 2022-05-21T05:12:48Z | - |
dc.date.issued | 2021-11-03 | - |
dc.identifier.citation | Mobashar Hussain Urf Turabe Fazil, Chandra Sekhar Chirumamilla, Claudina Perez-Novo, Brandon Han Siang Wong, Sunil Kumar, Siu Kwan Sze, Wim Vanden Berghe, Navin Kumar Verma (2021). The steroidal lactone withaferin A impedes T-cell motility by inhibiting the kinase ZAP70 and subsequent kinome signaling, Journal of Biological Chemistry, 297(6), 101377. | en_US |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | http://krishi.icar.gov.in/jspui/handle/123456789/72347 | - |
dc.description | Not Available | en_US |
dc.description.abstract | The steroidal lactone withaferin A (WFA) is a dietary phytochemical, derived from Withania somnifera. It exhibits a wide range of biological properties, including immunomodulatory, anti-inflammatory, antistress, and anticancer activities. Here we investigated the effect of WFA on T-cell motility, which is crucial for adaptive immune responses as well as autoimmune reactions. We found thatWFA dose-dependently (within the concentration range of 0.3–1.25 μM) inhibited the ability of human T-cells to migrate via cross-linking of the lymphocyte function-associated antigen-1 (LFA-1) integrin with its ligand, intercellular adhe sion molecule 1 (ICAM-1). Coimmunoprecipitation of WFA interacting proteins and subsequent tandem mass spectrometry identified a WFA-interactome consisting of 273 proteins in motile T-cells. In particular, our data revealed significant enrichment of the zeta-chain-associated protein kinase 70 (ZAP70) and cytoskeletal actin protein interaction networks upon stimulation. Phospho-peptide mapping and kinome anal ysis substantiated kinase signaling downstream of ZAP70 as a key WFA target, which was further confirmed by bait-pulldown and Western immunoblotting assays. The WFA-ZAP70 interaction was disrupted by a disulfide reducing agent dithiothreitol, sug gesting an involvement of cysteine covalent binding interface. In silico docking predicted WFA binding to ZAP70 at cystine 560 and 564 residues. These findings provide a mechanistic insight whereby WFA binds to and inhibits the ZAP70 kinase and im pedes T-cell motility. We therefore conclude that WFA may be exploited to pharmacologically control host immune responses and potentially prevent autoimmune-mediated pathologies | en_US |
dc.description.sponsorship | Not Available | en_US |
dc.language.iso | English | en_US |
dc.publisher | Not Available | en_US |
dc.relation.ispartofseries | Not Available; | - |
dc.subject | T-cell Motility | en_US |
dc.subject | Molecular Modelling | en_US |
dc.subject | Docking | en_US |
dc.subject | ZAP70 | en_US |
dc.title | The steroidal lactone withaferin A impedes T-cell motility by inhibiting the kinase ZAP70 and subsequent kinome signaling | en_US |
dc.type | Research Paper | en_US |
dc.publication.projectcode | Not Available | en_US |
dc.publication.journalname | Journal of Biological Chemistry | en_US |
dc.publication.volumeno | 297(6) | en_US |
dc.publication.pagenumber | 101377 | en_US |
dc.publication.divisionUnit | Not Available | en_US |
dc.publication.sourceUrl | https://doi.org/10.1016/j.jbc.2021.101377 | en_US |
dc.publication.authorAffiliation | Nanyang Technological University Singapore | en_US |
dc.publication.authorAffiliation | University of Antwerp, Wilrijk, Belgium | en_US |
dc.publication.authorAffiliation | ICAR-National Bureau of Agriculturally Important Microorganisms, Kushmaur, Mau, Uttar Pradesh, India | en_US |
dc.publication.authorAffiliation | ICAR::Indian Agricultural Statistics Research Institute | en_US |
dc.ICARdataUseLicence | http://krishi.icar.gov.in/PDF/ICAR_Data_Use_Licence.pdf | en_US |
dc.publication.naasrating | 11.15 | en_US |
dc.publication.impactfactor | 5.15 | en_US |
Appears in Collections: | AEdu-IASRI-Publication |
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