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Proteasome gene expression is controlled by coordinated functions of multiple transcription factors

J Cell Biol. 2024-08; 
Jennifer E Gilda, Asrafun Nahar, Dharanibalan Kasiviswanathan, Nadav Tropp, Tamar Gilinski, Tamar Lahav, Dina Alexandrovich, Yael Mandel-Gutfreund, Soyeon Park, Shenhav Shemer
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摘要

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 ... More

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