{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T18:34:47Z","timestamp":1751481287200},"reference-count":49,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2012,9,5]],"date-time":"2012-09-05T00:00:00Z","timestamp":1346803200000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:p>Lymphocyte activation results in profound changes in the abundance of m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> transcripts many of which are downregulated. The <jats:styled-content style=\"fixed-case\">W<\/jats:styled-content>iskott\u2013<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>ldrich syndrome (WAS) protein (<jats:styled-content style=\"fixed-case\">WASP<\/jats:styled-content>) family is critical for productive T\u2010cell receptor signaling and actin reorganization. The <jats:styled-content style=\"fixed-case\">WASP<\/jats:styled-content> signal pathway includes the WAS\/WAS\u2010like (WASL) interacting protein family 2 (<jats:styled-content style=\"fixed-case\">WIPF<\/jats:styled-content>2) gene also known as <jats:styled-content style=\"fixed-case\">WIRE<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">WICH<\/jats:styled-content>. We show that both human <jats:italic>WIPF2<\/jats:italic> and mouse <jats:italic>Wipf2<\/jats:italic> are mice, alternatively spliced within the 3\u2032 untranslated region (3\u2032<jats:styled-content style=\"fixed-case\">UTR<\/jats:styled-content>) resulting in two major transcripts of approximately 4.5 and 6 kb in size. Following T\u2010cell activation, the level of human <jats:italic>WIPF2<\/jats:italic> and mouse <jats:italic><jats:styled-content style=\"fixed-case\">Wipf2<\/jats:styled-content><\/jats:italic> m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> rapidly declines. In mice, this decline is accompanied by a marked reduction in <jats:styled-content style=\"fixed-case\">WIPF<\/jats:styled-content>2 protein levels. Transgenic expression of a 240\u2010bp fragment derived from a highly conserved terminal 3\u2032<jats:styled-content style=\"fixed-case\">UTR<\/jats:styled-content> found within the 6\u2010kb transcript blocks <jats:italic><jats:styled-content style=\"fixed-case\">W<\/jats:styled-content>ipf2<\/jats:italic> downregulation. These effects may be mediated by competitive inhibition of microinhibitory <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> (mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>) regulation since the 6\u2010kb\u2010derived transgene and the 4.5\u2010kb transcript share functional binding sites for mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>146a. Blocking <jats:italic><jats:styled-content style=\"fixed-case\">W<\/jats:styled-content>ipf2<\/jats:italic> gene and protein repression resulted in improved T\u2010cell responses to antigen immunization in vivo as well as in vitro cytotoxic T\u2010cell killing. Collectively, these data suggest that early downregulation of this immunologically relevant gene controls the intensity of selective lymphocyte functions.<\/jats:p>","DOI":"10.1002\/eji.201141533","type":"journal-article","created":{"date-parts":[[2012,6,4]],"date-time":"2012-06-04T17:16:11Z","timestamp":1338830171000},"page":"2409-2418","source":"Crossref","is-referenced-by-count":2,"title":["Inhibiting <scp>Wipf2<\/scp> downregulation by transgenic expression of its 3\u2032 m<scp>RNA<\/scp>\u2010untranslated region improves cytotoxicity and vaccination response"],"prefix":"10.1002","volume":"42","author":[{"given":"Oleh","family":"Pankewycz","sequence":"first","affiliation":[{"name":"Department of Surgery School of Medicine and Biomedical Sciences University at Buffalo  Buffalo NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Julian","family":"Ambrus","sequence":"additional","affiliation":[{"name":"Department of Medicine School of Medicine and 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