Use este identificador para citar o ir al link de este elemento:
http://hdl.handle.net/1843/61816
Tipo: | Artigo de Periódico |
Título: | DYT-PRKRA Mutation P222L Enhances PACT’s Stimulatory Activity on Type I Interferon Induction |
Autor(es): | Lauren S. Vaughn Kenneth Frederick Samuel B. Burnett Nutan Sharma D. Cristopher Bragg Sarah Teixeira Camargos Francisco Cardoso Rekha C. Patel |
Resumen: | 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. |
Asunto: | Distonia Receptores de Interferon Interferon Tipo I |
Idioma: | eng |
País: | Brasil |
Editor: | Universidade Federal de Minas Gerais |
Sigla da Institución: | UFMG |
Departamento: | HCL - HOSPITAL DAS CLINICAS MED - DEPARTAMENTO DE CLÍNICA MÉDICA |
Tipo de acceso: | Acesso Aberto |
Identificador DOI: | https://doi.org/10.3390/biom12050713 |
URI: | http://hdl.handle.net/1843/61816 |
Fecha del documento: | 2022 |
metadata.dc.url.externa: | https://www.mdpi.com/2218-273X/12/5/713 |
metadata.dc.relation.ispartof: | Biomolecules |
Aparece en las colecciones: | Artigo de Periódico |
archivos asociados a este elemento:
archivo | Descripción | Tamaño | Formato | |
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DYT-PRKRA Mutation P222L Enhances PACT’s Stimulatory Activity on Type I Interferon Induction.pdf | 2.2 MB | Adobe PDF | Visualizar/Abrir |
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