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http://hdl.handle.net/1843/61816| Type: | Artigo de Periódico |
| Title: | DYT-PRKRA Mutation P222L Enhances PACT’s Stimulatory Activity on Type I Interferon Induction |
| Authors: | Lauren S. Vaughn Kenneth Frederick Samuel B. Burnett Nutan Sharma D. Cristopher Bragg Sarah Teixeira Camargos Francisco Cardoso Rekha C. Patel |
| Abstract: | 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’s 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’s ability to induce IFN β in response to dsRNA and the basal expression of IFN β and IFN-stimulated genes (ISGs) is higher in DYT-PRKRA patient cells compared to cells from the unaffected controls. Additionally, IFN β 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. |
| Subject: | Distonia Receptores de Interferon Interferon Tipo I |
| language: | eng |
| metadata.dc.publisher.country: | Brasil |
| Publisher: | Universidade Federal de Minas Gerais |
| Publisher Initials: | UFMG |
| metadata.dc.publisher.department: | HCL - HOSPITAL DAS CLINICAS MED - DEPARTAMENTO DE CLÍNICA MÉDICA |
| Rights: | Acesso Aberto |
| metadata.dc.identifier.doi: | https://doi.org/10.3390/biom12050713 |
| URI: | http://hdl.handle.net/1843/61816 |
| Issue Date: | 2022 |
| metadata.dc.url.externa: | https://www.mdpi.com/2218-273X/12/5/713 |
| metadata.dc.relation.ispartof: | Biomolecules |
| Appears in Collections: | Artigo de Periódico |
Files in This Item:
| File | Description | Size | Format | |
|---|---|---|---|---|
| DYT-PRKRA Mutation P222L Enhances PACT’s Stimulatory Activity on Type I Interferon Induction.pdf | 2.2 MB | Adobe PDF | View/Open |
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