{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T16:29:19Z","timestamp":1770913759096,"version":"3.50.1"},"reference-count":93,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T00:00:00Z","timestamp":1652745600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dystonia Medical Research Foundation grant and a University of South Carolina ASPIRE","award":["R.C.P."],"award-info":[{"award-number":["R.C.P."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>DYT-PRKRA (dystonia 16 or DYT-PRKRA) is caused by mutations in the PRKRA gene that encodes PACT, the protein activator of interferon (IFN)-induced double-stranded (ds) RNA-activated protein kinase (PKR). PACT participates in several cellular pathways, of which its role as a PKR activator protein during integrated stress response (ISR) is the best characterized. Previously, we have established that the DYT-PRKRA mutations cause enhanced activation of PKR during ISR to sensitize DYT-PRKRA cells to apoptosis. In this study, we evaluate if the most prevalent substitution mutation reported in DYT-PRKRA patients alters PACT\u2019s functional role in induction of type I IFNs via the retinoic acid-inducible gene I (RIG-I) signaling. Our results indicate that the P222L mutation augments PACT\u2019s ability to induce IFN \u03b2 in response to dsRNA and the basal expression of IFN \u03b2 and IFN-stimulated genes (ISGs) is higher in DYT-PRKRA patient cells compared to cells from the unaffected controls. Additionally, IFN \u03b2 and ISGs are also induced at higher levels in DYT-PRKRA cells in response to dsRNA. These results offer a new avenue for investigations directed towards understanding the underlying molecular pathomechanisms in DYT-PRKRA.<\/jats:p>","DOI":"10.3390\/biom12050713","type":"journal-article","created":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T08:34:29Z","timestamp":1652776469000},"page":"713","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["DYT-PRKRA Mutation P222L Enhances PACT\u2019s Stimulatory Activity on Type I Interferon Induction"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2282-6738","authenticated-orcid":false,"given":"Lauren S.","family":"Vaughn","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, University of South Carolina, 700 Sumter Street, Columbia, SC 29208, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth","family":"Frederick","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of South Carolina, 700 Sumter Street, Columbia, SC 29208, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel B.","family":"Burnett","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of South Carolina, 700 Sumter Street, Columbia, SC 29208, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nutan","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital, Charlestown, MA 02129, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. Cristopher","family":"Bragg","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital, Charlestown, MA 02129, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Camargos","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rekha C.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of South Carolina, 700 Sumter Street, Columbia, SC 29208, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/S1474-4422(06)70547-6","article-title":"The diagnosis of dystonia","volume":"5","author":"Geyer","year":"2006","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.nbd.2010.11.015","article-title":"Molecular pathways in dystonia","volume":"42","author":"Bragg","year":"2011","journal-title":"Neurobiol. 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