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

GSE283266 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2025/01/13 Platform GPL30172
Summary
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.
Published in
The DYT6 dystonia causative protein THAP1 is responsible for proteasome activity via PSMB5 transcriptional regulation
Wang Y, Wang Y, Iriki T et al. · Nature communications 2025 · PMID 39952963 · doi:10.1038/s41467-025-56867-x
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Also filed as BioProject PRJNA1192990 and SRA study SRP548654. Searching any of these in the dataset finder brings you back here.

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