Mutation in Prkra results in cerebellar abnormality and reduced eIF2α phosphorylation in a model of DYT-PRKRA.

ABSTRACT: Variants in the PRKRA gene, which encodes PACT, cause the early-onset primary dystonia DYT-PRKRA, a movement disorder associated with disruption of coordinated muscle movements. PACT and its murine homolog RAX activate protein kinase R (PKR; also known as EIF2AK2) by a direct interaction in response to cellular stressors to mediate phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α). Mice homozygous for a naturally arisen, recessively inherited frameshift mutation, Prkralear-5J, exhibit progressive dystonia. In the present study, we investigated the biochemical and developmental consequences of the Prkralear-5J mutation. Our results indicated that the truncated PACT/RAX protein retains its ability to interact with PKR but inhibits PKR activation. Mice hom

SUBMITTER: Burnett SB 

PROVIDER: S-EPMC11625895 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature