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The DYT6 dystonia causative protein THAP1 is responsible for proteasome activity via PSMB5 transcriptional regulation

ABSTRACT: The proteasome plays a pivotal role in protein degradation, and its impairment is associated with various pathological conditions, including neurodegenerative diseases. It is well understood that Nrf1 coordinates the induction of all proteasome genes in response to proteasome dysfunction. However, the molecular mechanism regulating the basal expression of the proteasome remains unclear. Here we identified the transcription factor THAP1, the causative gene of DYT6 dystonia, as a regulator of proteasome activity through genome-wide genetic screens. We demonstrated that THAP1 directly regulates the expression of the PSMB5 gene, which encodes the central protease subunit β5. Depletion of THAP1 disrupted proteasome assembly, leading to reduced proteasome activity and the accumulation of ubiquitinated proteins. These findings reveal a new regulatory mechanism for the proteasome and suggest a potential role for proteasome dysfunction in the pathogenesis of dystonia.

ORGANISM(S): Mus musculus

PROVIDER: GSE283266 | GEO | 2025/01/13

REPOSITORIES: GEO

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The DYT6 dystonia causative protein THAP1 is responsible for proteasome activity via PSMB5 transcriptional regulation

Project description:The DYT6 dystonia causative protein THAP1 is responsible for proteasome activity via PSMB5 transcriptional regulation

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THAP1 is cell type dependent regulator of SP1 family crucial for dystonic syndromes in human and rat [Striatum_RNA-seq]

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The Dystonia Gene THAP1 Controls DNA Double Strand Break Repair Choice [ChIP-Seq]

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