Chromosome alignment-maintaining phosphoprotein CHAMP1 plays a role in cell survival through regulating Mcl-1 expression

Research output: Contribution to journalArticlepeer-review

Abstract

Antimitotic drugs such as vinca alkaloids and taxanes cause mitotic cell death after prolonged mitotic arrest. However, a fraction of cells escape from mitotic arrest by undergoing mitotic slippage, which is related to resistance to antimitotic drugs. Tipping the balance to mitotic cell death thus can be a way to overcome the drug resistance. Here we found that depletion of a mitotic regulator, CHAMP1 (chromosome alignment-maintaining phosphoprotein, CAMP), accelerates the timing of mitotic cell death after mitotic arrest. Live cell imaging revealed that CHAMP1-depleted cells died earlier than mock-treated cells in the presence of antimitotic drugs that resulted in the reduction of cells undergoing mitotic slippage. Depletion CHAMP1 reduces the expression of antiapoptotic Bcl-2 family proteins, especially Mcl-1. We found that CHAMP1 maintains Mcl-1 expression both at protein and mRNA levels independently of the cell cycle. At the protein level, CHAMP1 maintains Mcl-1 stability by suppressing proteasome-dependent degradation. Depletion of CHAMP1 reduces cell viability, and exhibits synergistic effects with antimitotic drugs. Our data suggest that CHAMP1 plays a role in the maintenance of Mcl-1 expression, implying that CHAMP1 can be a target to overcome the resistance to antimitotic drugs.

Original languageEnglish
Pages (from-to)3711-3721
Number of pages11
JournalCancer science
Volume112
Issue number9
DOIs
Publication statusPublished - 2021 Sep

Keywords

  • CHAMP1
  • Mcl-1
  • anticancer drug resistance
  • apoptosis
  • mitotic cell death

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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