Early recovery of proteasome activity in cells pulse-treated with proteasome inhibitors is independent of DDI2.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38619391.
- Also identified by DOI 10.7554/eLife.91678 and PMC identifier 11018354.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Proteasome Endopeptidase Complex
- Proteasome Inhibitors