Bibliographic Details
| Title: |
The DYT6 dystonia causative protein THAP1 is responsible for proteasome activity via PSMB5 transcriptional regulation. |
| Authors: |
Wang, Yan, Wang, Yi, Iriki, Tomohiro, Hashimoto, Eiichi, Inami, Maki, Hashimoto, Sota, Watanabe, Ayako, Takano, Hiroshi, Motosugi, Ryo, Hirayama, Shoshiro, Sugishita, Hiroki, Gotoh, Yukiko, Yao, Ryoji, Hamazaki, Jun, Murata, Shigeo |
| Source: |
Nature Communications; 2/14/2025, Vol. 16, p1-14, 14p |
| Subject Terms: |
TRANSCRIPTION factors, GENE expression, GENETIC testing, PROTEOLYSIS, LIFE sciences |
| 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 identify the transcription factor THAP1, the causative gene of DYT6 dystonia, as a regulator of proteasome activity through a genome-wide genetic screen. We demonstrated that THAP1 directly regulates the expression of the PSMB5 gene, which encodes the central protease subunit β5. Depletion of THAP1 disrupts proteasome assembly, leading to reduced proteasome activity and the accumulation of ubiquitinated proteins. These findings uncover a regulatory mechanism for the proteasome and suggest a potential role for proteasome dysfunction in the pathogenesis of dystonia. The proteasome is crucial for protein degradation, and its dysfunction is linked to various pathologies. Here, the authors show that the transcription factor THAP1, the causative gene for DYT6 dystonia, is essential for proteasome activity by regulating the expression of the core β5 subunit. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
