DDI2 promotes tumor metastasis and resists antineoplastic drugs-induced apoptosis in colorectal cancer

Lei, Lei; Cao, Qing; An, Guoyan; Lv, Yuejiao; Tang, Juan; Yang, Jin

doi:10.1007/s10495-022-01796-z

“…In summary, our study provides strong evidence for a novel pathway responsible for the recovery of proteasome activity in inhibitor-treated cells. It should stimulate research on additional biological roles of DDI2, which can explain the embryonic lethality of DDI2 deletion ( Siva et al, 2020 ) and DDI2’s role in tumorigenesis ( Lei et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

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

Ibtisam,

Kisselev

2024

eLife

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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.

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“…In summary, our study provides strong evidence for a novel pathway responsible for the recovery of proteasome activity in inhibitor-treated cells. It should stimulate research on additional biological roles of DDI2, which can explain the embryonic lethality of DDI2 deletion [23] and DDI2's role in tumorigenesis [41].…”

Section: Discussionmentioning

confidence: 99%

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

Ibtisam,

Kisselev

2023

Preprint

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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.

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DDI2 protease controls embryonic development and inflammation via TCF11/NRF1

Nedomova,

Haberecht-Müller,

Möller

et al. 2024

iScience

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DDI2 promotes tumor metastasis and resists antineoplastic drugs-induced apoptosis in colorectal cancer

Cited by 5 publications

References 28 publications

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

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

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

DDI2 protease controls embryonic development and inflammation via TCF11/NRF1

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