NEDD8-activating enzyme inhibition induces cell cycle arrest and anaphase catastrophe in malignant T-cells

Oncotarget. 2021 Sep 28;12(20):2068-2074. doi: 10.18632/oncotarget.28063. eCollection 2021 Sep 28.ABSTRACTPeripheral T-cell lymphoma (PTCL) is characterized by poor outcomes. We and others have shown that targeting the NEDD8-activating enzyme (NAE) with an investigational inhibitor pevonedistat deregulates cell cycle and mitosis in lymphoma and leukemia. Here, we report that PTCL is characterized by increased rate of chromosomal instability. NAE inhibition promotes cell cycle arrest and induces multipolar anaphases in T-cell lymphoma cell lines, resulting in apoptosis, also observed in primary malignant PTCL cells treated with pevonedistat. We identified p27Kip1 as a mediator of anaphase catastrophe in these cells. Targeting neddylation with pevonedistat may be a promising approach to treatment of PTCL.PMID:34611480 | PMC:PMC8487718 | DOI:10.18632/oncotarget.28063

Source: Oncotarget - October 6, 2021 Category: Cancer & Oncology Authors: Adam S Kittai Olga V Danilova Vi Lam Tingting Liu Nur Bruss Scott Best Guang Fan Alexey V Danilov Source Type: research