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| Status |
Public on May 01, 2024 |
| Title |
Proteasome gene expression is controlled by the coordinated functions of multiple transcription factors |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Proteasome activity is crucial for cellular integrity, but how tissues adjust proteasome content in response to catabolic stimuli is uncertain. Here, we demonstrate that transcriptional coordination by multiple transcription factors is required to increase proteasome content and activate proteolysis in catabolic states. Using denervated mouse muscle as a model system for accelerated proteolysis in vivo, we reveal that a two-phase transcriptional program activates genes encoding proteasome subunits and assembly chaperones to boost an increase in proteasome content. Initially, gene induction is necessary to maintain basal proteasome levels, and in a more delayed phase (7-10 d after denervation) it stimulates proteasome assembly to meet cellular demand for excessive proteolysis. Intriguingly, the transcription factors PAX4 and α-PALNRF-1 control the expression of proteasome among other genes in a combinatorial manner, driving cellular adaptation to muscle denervation. Consequently, PAX4 and α-PALNRF-1 represent new therapeutic targets to inhibit proteolysis in catabolic diseases (e.g. type-2 diabetes, cancer).
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| Overall design |
WT and transgenic animals are subjected to muscle denervation and gene expression analyses are performed on their muscles.
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| Contributor(s) |
Cohen S, Mandel-Gutfreund Y |
| Citation missing |
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| |
| Submission date |
May 11, 2023 |
| Last update date |
May 01, 2024 |
| Contact name |
Tamar Lahav |
| E-mail(s) |
lahav008@gmail.com
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| Organization name |
Technion
|
| Department |
Biology
|
| Street address |
Zor
|
| City |
Haifa |
| ZIP/Postal code |
20345 |
| Country |
Israel |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (23)
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| Relations |
| BioProject |
PRJNA971654 |
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