DYT-PRKRA Mutation P222L Enhances PACT’s Stimulatory Activity on Type I Interferon Induction

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dc.creatorLauren S. Vaughn
dc.creatorKenneth Frederick
dc.creatorSamuel B. Burnett
dc.creatorNutan Sharma
dc.creatorD. Cristopher Bragg
dc.creatorSarah Teixeira Camargos
dc.creatorFrancisco Cardoso
dc.creatorRekha C. Patel
dc.date.accessioned2023-12-06T19:35:59Z
dc.date.accessioned2025-09-09T00:34:50Z
dc.date.available2023-12-06T19:35:59Z
dc.date.issued2022
dc.format.mimetypepdf
dc.identifier.doihttps://doi.org/10.3390/biom12050713
dc.identifier.issn2218-273X
dc.identifier.urihttps://hdl.handle.net/1843/61816
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofBiomolecules
dc.rightsAcesso Aberto
dc.subjectDistonia
dc.subjectReceptores de Interferon
dc.subjectInterferon Tipo I
dc.subject.otherDystonia
dc.subject.otherDYT16
dc.subject.otherDYT-PRKRA
dc.subject.otherPACT
dc.subject.otherPRKRA
dc.subject.otherPKR
dc.subject.otherInterferon
dc.subject.otherRIG-I
dc.titleDYT-PRKRA Mutation P222L Enhances PACT’s Stimulatory Activity on Type I Interferon Induction
dc.typeArtigo de periódico
local.citation.issue5
local.citation.volume12
local.description.resumoDYT-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.
local.identifier.orcidhttps://orcid.org/0000-0003-2282-6738
local.publisher.countryBrasil
local.publisher.departmentHCL - HOSPITAL DAS CLINICAS
local.publisher.departmentMED - DEPARTAMENTO DE CLÍNICA MÉDICA
local.publisher.initialsUFMG
local.url.externahttps://www.mdpi.com/2218-273X/12/5/713

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