20 min listen
Proteasome gene expression is controlled by the coordinated functions of multiple transcription factors
Proteasome gene expression is controlled by the coordinated functions of multiple transcription factors
ratings:
Length:
20 minutes
Released:
Apr 13, 2023
Format:
Podcast episode
Description
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2023.04.12.536627v1?rss=1
Authors: Gilda, J. E., Nahar, A., Kasiviswanathan, D., Tropp, N., Gilinski, T., Lahav, T., Mandel-Gutfreund, Y., Park, S., Cohen, S.
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 d after denervation) it stimulates proteasome assembly to meet cellular demand for excessive proteolysis. Intriguingly, the transcription factors PAX4 and -PALNRF-1 control the expression of proteasome among other genes in a combinatorial manner, driving cellular adaptation to muscle denervation. Consequently, PAX4 and -PALNRF-1 represent new therapeutic targets to inhibit proteolysis in catabolic diseases (e.g. type-2 diabetes, cancer).
Copy rights belong to original authors. Visit the link for more info
Podcast created by Paper Player, LLC
http://biorxiv.org/cgi/content/short/2023.04.12.536627v1?rss=1
Authors: Gilda, J. E., Nahar, A., Kasiviswanathan, D., Tropp, N., Gilinski, T., Lahav, T., Mandel-Gutfreund, Y., Park, S., Cohen, S.
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 d after denervation) it stimulates proteasome assembly to meet cellular demand for excessive proteolysis. Intriguingly, the transcription factors PAX4 and -PALNRF-1 control the expression of proteasome among other genes in a combinatorial manner, driving cellular adaptation to muscle denervation. Consequently, PAX4 and -PALNRF-1 represent new therapeutic targets to inhibit proteolysis in catabolic diseases (e.g. type-2 diabetes, cancer).
Copy rights belong to original authors. Visit the link for more info
Podcast created by Paper Player, LLC
Released:
Apr 13, 2023
Format:
Podcast episode
Titles in the series (100)
Endosomal removal and disposal of dysfunctional, immunostimulatory mitochondrial DNA by PaperPlayer biorxiv cell biology