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Recovery of proteasome activity in cells pulse-treated with proteasome inhibitors is independent of DDI2.

ABSTRACT: Rapid recovery of proteasome activity may contribute to intrinsic and acquired resistance to FDA-approved proteasome inhibitors. Previous studies have demonstrated that the expression of proteasome genes in cells treated with sub-lethal concentrations of proteasome inhibitors is upregulated by the transcription factor Nrf1 (NFE2L1), which is activated by a novel DDI2 protease. Here we demonstrate that the recovery of proteasome activity is DDI2-independent and occurs before the upregulation of proteasome gene expression. The recovery requires protein translation, but the efficiency of translation of proteasomal mRNA does not increase upon proteasome inhibition. Based on this data, we propose that the increased efficiency of proteasome assembly is responsible for the recovery of proteasome activity.

SUBMITTER: Ibtisam I

PROVIDER: S-EPMC10418215 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Early recovery of proteasome activity in cells pulse-treated with proteasome inhibitors is independent of DDI2.

Ibtisam Ibtisam I Kisselev Alexei F AF

bioRxiv : the preprint server for biology 20231128

Rapid recovery of proteasome activity may contribute to intrinsic and acquired resistance to FDA-approved proteasome inhibitors. Previous studies have demonstrated that the expression of proteasome genes in cells treated with sub-lethal concentrations of proteasome inhibitors is upregulated by the transcription factor Nrf1 (NFE2L1), which is activated by a DDI2 protease. Here, we demonstrate that the recovery of proteasome activity is DDI2-independent and occurs before transcription of proteasom ...[more]

PMID: 37577495

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Early recovery of proteasome activity in cells pulse-treated with proteasome inhibitors is independent of DDI2.

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Multiple myeloma cells depend on the DDI2/NRF1-mediated proteasome stress response for survival.

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Activating the NFE2L1-ubiquitin-proteasome system by DDI2 protects from ferroptosis.

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Suppression of BRCA1 sensitizes to proteasome inhibitors in DNA repair-independent manner.

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Suppression of BRCA1 sensitizes to proteasome inhibitors in DNA repair-independent manner.

2015-01-01 | GSE56280 | GEO