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Impact of PPP1R1A Knockdown on the Proteomic Landscape of INS-1 Cells: A Focus on Significant Modulated Pathways

2025-12-08Artigo científico Acesso aberto
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datacite.subject.fosCiências Naturais::Ciências Biológicas
dc.contributor.authorTaneera, Jalal
dc.contributor.authorGiddey, Alexander D.
dc.contributor.authorSoares, Nelson C.
dc.contributor.authorKhalique, Anila
dc.contributor.authorMohammed, Abdul Khader
dc.contributor.authorMahgoub, Mohamed Omer
dc.contributor.authorMahgoub, Eglal
dc.date.accessioned2026-01-29T12:21:12Z
dc.date.available2026-01-29T12:21:12Z
dc.date.issued2025-12-08
dc.description.abstractPPP1R1A (protein phosphatase 1 regulatory inhibitor subunit 1A) is a cAMP/PKA-responsive inhibitor of protein phosphatase 1 (PP1) with a pivotal role in pancreatic β-cell physiology. To investigate its functional impact, Ppp1r1a was silenced in INS-1 (832/13) rat β-cells, and proteomic alterations were profiled using label-free DIA mass spectrometry (Orbitrap Exploris 480) with a rat spectral library. Quantitative analysis (n = 4/group) identified ∼2846 proteins with >2-fold change, revealing extensive proteome reprogramming. Key biological processes affected included vesicle trafficking and exocytosis, insulin biosynthesis and processing, organelle organization, mRNA processing, and autophagy. Pathway enrichment highlighted disruptions in insulin secretion, insulin resistance, and mTOR signaling. Crucial β-cell proteins, including INS2, Cacna1a, CPEB2, PCSK2, SNAP25, SYT5, and VAMP7, were significantly downregulated. Validation confirmed reduced phosphorylated AKT levels and p-AKT/T-AKT ratio, consistent with impaired mTOR signaling. Collectively, these findings demonstrate that PPP1R1A is essential for maintaining β-cell function and insulin secretion, and its depletion triggers broad proteomic and signaling alterations. Thus, PPP1R1A emerges as a regulatory node with potential therapeutic relevance in modulating β-cell activity and insulin dynamics in diabetes.eng
dc.identifier.citationJ Proteome Res. 2026 Jan 2;25(1):460-470. doi: 10.1021/acs.jproteome.5c00889. Epub 2025 Dec 8.
dc.identifier.doi10.1021/acs.jproteome.5c00889
dc.identifier.issn1535-3893
dc.identifier.pmid41359828
dc.identifier.urihttp://hdl.handle.net/10400.18/10783
dc.language.isoeng
dc.peerreviewedyes
dc.publisherAmerican Chemical Society
dc.relation.hasversionhttps://pubs.acs.org/doi/10.1021/acs.jproteome.5c00889
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAKT Phosphorylation
dc.subjectPPP1R1A
dc.subjectInsulin Secretion
dc.subjectmTOR Signaling
dc.subjectPancreatic β-cells
dc.subjectProteomics
dc.subjectGenómica Funcional e Estrutural
dc.titleImpact of PPP1R1A Knockdown on the Proteomic Landscape of INS-1 Cells: A Focus on Significant Modulated Pathwayspor
dc.typejournal article
dcterms.referenceshttps://pubs.acs.org/doi/10.1021/acs.jproteome.5c00889
dspace.entity.typePublication
oaire.citation.endPage470
oaire.citation.issue1
oaire.citation.startPage460
oaire.citation.titleJournal of Proteome Research
oaire.citation.volume25
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

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