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Oxidative stress and endoplasmic reticulum (ER) stress causes PACT\u2010mediated PKR activation, which leads to phosphorylation of translation initiation factor eIF2\u03b1, inhibition of protein synthesis, and apoptosis. A dominantly inherited form of early\u2010onset dystonia 16 (DYT16) has been identified to arise due to a frameshift (FS) mutation in PACT. To examine the effect of the resulting truncated mutant PACT protein on the PKR pathway, we examined the biochemical properties of the mutant protein and its effect on mammalian cells. Our results indicate that the FS mutant protein loses its ability to bind dsRNA as well as its ability to interact with PKR while surprisingly retaining the ability to interact with PACT and PKR\u2010inhibitory protein TRBP. The truncated FS mutant protein, when expressed as a fusion protein with a N\u2010terminal fluorescent mCherry tag aggregates in mammalian cells to induce apoptosis via activation of caspases both in a PKR\u2010 and PACT\u2010dependent as well as independent manner. Our results indicate that interaction of FS mutant protein with PKR inhibitor TRBP can dissociate PACT from the TRBP\u2010PACT complex resulting in PKR activation and consequent apoptosis. These findings are relevant to diseases resulting from protein aggregation especially since the PKR activation is a characteristic of several neurodegenerative conditions.<\/jats:p>","DOI":"10.1002\/jcb.29223","type":"journal-article","created":{"date-parts":[[2019,6,27]],"date-time":"2019-06-27T12:59:46Z","timestamp":1561640386000},"page":"19004-19018","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["A truncated PACT protein resulting from a frameshift mutation reported in movement disorder DYT16 triggers caspase activation and apoptosis"],"prefix":"10.1002","volume":"120","author":[{"given":"Samuel B","family":"Burnett","sequence":"first","affiliation":[{"name":"Department of Biological Sciences University of South Carolina University of South Carolina  Columbia South Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren 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