Early recovery of proteasome activity in cells pulse-treated with proteasome inhibitors is independent of DDI2.
| Autor: | Ibtisam I; Department of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, 720 S. Donahue Dr. Auburn AL 36849 USA., Kisselev AF; Department of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, 720 S. Donahue Dr. Auburn AL 36849 USA. |
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| Jazyk: | angličtina |
| Zdroj: | BioRxiv : the preprint server for biology [bioRxiv] 2023 Nov 28. Date of Electronic Publication: 2023 Nov 28. |
| DOI: | 10.1101/2023.08.03.550647 |
| Abstrakt: | 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. Competing Interests: Conflict of interest statement AFK is a Co-founder and Chief Scientific Officer of InhiProt, LLC. |
| Databáze: | MEDLINE |
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