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bioRxiv · 10.1101/2023.08.03.550647

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

Ibtisam, I.·Kisselev, A. F.
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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.

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Ibtisam, I., Kisselev, A. F.. 2023-08-04. Recovery of proteasome activity in cells pulse-treated with proteasome inhibitors is independent of DDI2. https://doi.org/10.1101/2023.08.03.550647

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