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

Adam S. Kittai, Olga V. Danilova, Vi Lam, Tingting Liu, Nur Bruss, Scott Best, Guang Fan, Alexey V. Danilov

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Peripheral 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.

Original languageEnglish (US)
Pages (from-to)2068-2074
Number of pages7
JournalOncotarget
Volume12
Issue number20
DOIs
StatePublished - Sep 28 2021

Keywords

  • Anaphase catastrophe
  • Chromosomal instability
  • Pevonedistat
  • T-cell lymphoma

ASJC Scopus subject areas

  • Oncology

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