{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T16:40:12Z","timestamp":1782837612593,"version":"3.54.5"},"reference-count":154,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,10,20]],"date-time":"2020-10-20T00:00:00Z","timestamp":1603152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1NS090949"],"award-info":[{"award-number":["RO1NS090949"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The oncogenic potential of both the polyomavirus large (LT-Ag) and small (Sm t-Ag) tumor antigens has been previously demonstrated in both tissue culture and animal models. Even the contribution of the MCPyV tumor antigens to the development of an aggressive human skin cancer, Merkel cell carcinoma, has been recently established. To date, the known primary targets of these tumor antigens include several tumor suppressors such as pRb, p53, and PP2A. However, a comprehensive list of the host proteins targeted by these proteins remains largely unknown. Here, we report the first interactome of JCV LT-Ag and Sm t-Ag by employing two independent \u201caffinity purification\/mass spectroscopy\u201d (AP\/MS) assays. The proteomics data identified novel targets for both tumor antigens while confirming some of the previously reported interactions. LT-Ag was found to primarily target the protein complexes with ATPase (v-ATPase and Smc5\/6 complex), phosphatase (PP4 and PP1), and ligase (E3-ubiquitin) activities. In contrast, the major targets of Sm t-Ag were identified as Smarca1\/6, AIFM1, SdhA\/B, PP2A, and p53. The interactions between \u201cLT-Ag and SdhB\u201d, \u201cSm t-Ag and Smarca5\u201d, and \u201cSm t-Ag and SDH\u201d were further validated by biochemical assays. Interestingly, perturbations in some of the LT-Ag and Sm t-Ag targets identified in this study were previously shown to be associated with oncogenesis, suggesting new roles for both tumor antigens in novel oncogenic pathways. This comprehensive data establishes new foundations to further unravel the new roles for JCV tumor antigens in oncogenesis and the viral life cycle.<\/jats:p>","DOI":"10.3390\/v12101192","type":"journal-article","created":{"date-parts":[[2020,10,20]],"date-time":"2020-10-20T09:28:23Z","timestamp":1603186103000},"page":"1192","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["A Comprehensive Proteomics Analysis of the JC Virus (JCV) Large and Small Tumor Antigen Interacting Proteins: Large T Primarily Targets the Host Protein Complexes with V-ATPase and Ubiquitin Ligase Activities While Small t Mostly Associates with Those Having Phosphatase and Chromatin-Remodeling Functions"],"prefix":"10.3390","volume":"12","author":[{"given":"Sami","family":"Saribas","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmut","family":"Safak","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.3389\/fmicb.2017.01557","article-title":"Protein\u2013Protein Interactions in Virus\u2013Host Systems","volume":"8","author":"Brito","year":"2017","journal-title":"Front. 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