Proteasome gene expression is controlled by coordinated functions of multiple transcription factors.
J Cell Biol
; 223(8)2024 Aug 05.
Article
em En
| MEDLINE
| ID: mdl-38767572
ABSTRACT
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 days 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).
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Complexo de Endopeptidases do Proteassoma
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Fator 1 Nuclear Respiratório
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Fatores de Transcrição Box Pareados
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Proteólise
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Israel