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Early 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 DDI2 protease. Here, we demonstrate that the recovery of proteasome activity is DDI2-independent and occurs before transcription of proteasomal genes is upregulated but requires protein translation. Thus, mammalian cells possess an additional DDI2 and transcription-independent pathway for the rapid recovery of proteasome activity after proteasome inhibition.

SUBMITTER: Ibtisam I

PROVIDER: S-EPMC11018354 | biostudies-literature | 2024 Apr

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

eLife 20240415

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: 38619391

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

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

2015-01-01 | GSE56280 | GEO